Daily Papers

We show that protein sequences can be thought of as sentences in natural language processing and can be parsed using the existing Quantum Natural Language framework into parameterized quantum circuits of reasonable qubits, which can be trained to solve various protein-related machine-learning problems. We classify proteins based on their subcellular locations, a pivotal task in bioinformatics that is key to understanding biological processes and disease mechanisms. Leveraging the quantum-enhanced processing capabilities, we demonstrate that Quantum Tensor Networks (QTN) can effectively handle the complexity and diversity of protein sequences. We present a detailed methodology that adapts QTN architectures to the nuanced requirements of protein data, supported by comprehensive experimental results. We demonstrate two distinct QTNs, inspired by classical recurrent neural networks (RNN) and convolutional neural networks (CNN), to solve the binary classification task mentioned above. Our top-performing quantum model has achieved a 94% accuracy rate, which is comparable to the performance of a classical model that uses the ESM2 protein language model embeddings. It's noteworthy that the ESM2 model is extremely large, containing 8 million parameters in its smallest configuration, whereas our best quantum model requires only around 800 parameters. We demonstrate that these hybrid models exhibit promising performance, showcasing their potential to compete with classical models of similar complexity.

Proteins are essential to life's processes, underpinning evolution and diversity. Advances in sequencing technology have revealed millions of proteins, underscoring the need for sophisticated pre-trained protein models for biological analysis and AI development. Facebook's ESM2, the most advanced protein language model to date, leverages a masked prediction task for unsupervised learning, crafting amino acid representations with notable biochemical accuracy. Yet, it lacks in delivering functional protein insights, signaling an opportunity for enhancing representation quality.Our study addresses this gap by incorporating protein family classification into ESM2's training.This approach, augmented with Community Propagation-Based Clustering Algorithm, improves global protein representations, while a contextual prediction task fine-tunes local amino acid accuracy. Significantly, our model achieved state-of-the-art results in several downstream experiments, demonstrating the power of combining global and local methodologies to substantially boost protein representation quality.

Current Large Language Models (LLMs) for understanding proteins primarily treats amino acid sequences as a text modality. Meanwhile, Protein Language Models (PLMs), such as ESM-2, have learned massive sequential evolutionary knowledge from the universe of natural protein sequences. Furthermore, structure-based encoders like ProteinMPNN learn the structural information of proteins through Graph Neural Networks. However, whether the incorporation of protein encoders can enhance the protein understanding of LLMs has not been explored. To bridge this gap, we propose EvoLlama, a multimodal framework that connects a structure-based encoder, a sequence-based protein encoder and an LLM for protein understanding. EvoLlama consists of a ProteinMPNN structure encoder, an ESM-2 protein sequence encoder, a multimodal projector to align protein and text representations and a Llama-3 text decoder. To train EvoLlama, we fine-tune it on protein-oriented instructions and protein property prediction datasets verbalized via natural language instruction templates. Our experiments show that EvoLlama's protein understanding capabilities have been significantly enhanced, outperforming other fine-tuned protein-oriented LLMs in zero-shot settings by an average of 1%-8% and surpassing the state-of-the-art baseline with supervised fine-tuning by an average of 6%. On protein property prediction datasets, our approach achieves promising results that are competitive with state-of-the-art task-specific baselines. We will release our code in a future version.

Multimodal protein language models deliver strong performance on mutation-effect prediction, but training such models from scratch demands substantial computational resources. In this paper, we propose a fine-tuning framework called InstructPLM-mu and try to answer a question: Can multimodal fine-tuning of a pretrained, sequence-only protein language model match the performance of models trained end-to-end? Surprisingly, our experiments show that fine-tuning ESM2 with structural inputs can reach performance comparable to ESM3. To understand how this is achieved, we systematically compare three different feature-fusion designs and fine-tuning recipes. Our results reveal that both the fusion method and the tuning strategy strongly affect final accuracy, indicating that the fine-tuning process is not trivial. We hope this work offers practical guidance for injecting structure into pretrained protein language models and motivates further research on better fusion mechanisms and fine-tuning protocols.

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its relevance to protein function. To address this issue, we introduce the integration of remote homology detection to distill structural information into protein language models without requiring explicit protein structures as input. We evaluate the impact of this structure-informed training on downstream protein function prediction tasks. Experimental results reveal consistent improvements in function annotation accuracy for EC number and GO term prediction. Performance on mutant datasets, however, varies based on the relationship between targeted properties and protein structures. This underscores the importance of considering this relationship when applying structure-aware training to protein function prediction tasks. Code and model weights are available at https://github.com/DeepGraphLearning/esm-s.

The rapid advancements in transformer-based language models have revolutionized natural language processing, yet understanding the internal mechanisms of these models remains a significant challenge. This paper explores the application of sparse autoencoders (SAE) to interpret the internal representations of protein language models, specifically focusing on the ESM-2 8M parameter model. By performing a statistical analysis on each latent component's relevance to distinct protein annotations, we identify potential interpretations linked to various protein characteristics, including transmembrane regions, binding sites, and specialized motifs. We then leverage these insights to guide sequence generation, shortlisting the relevant latent components that can steer the model towards desired targets such as zinc finger domains. This work contributes to the emerging field of mechanistic interpretability in biological sequence models, offering new perspectives on model steering for sequence design.

Predicting protein function from amino acid sequence remains a central challenge in data-scarce (low-N) regimes, limiting machine learning-guided protein design when only small amounts of assay-labeled sequence-function data are available. Protein language models (pLMs) have advanced the field by providing evolutionary-informed embeddings and sparse autoencoders (SAEs) have enabled decomposition of these embeddings into interpretable latent variables that capture structural and functional features. However, the effectiveness of SAEs for low-N function prediction and protein design has not been systematically studied. Herein, we evaluate SAEs trained on fine-tuned ESM2 embeddings across diverse fitness extrapolation and protein engineering tasks. We show that SAEs, with as few as 24 sequences, consistently outperform or compete with their ESM2 baselines in fitness prediction, indicating that their sparse latent space encodes compact and biologically meaningful representations that generalize more effectively from limited data. Moreover, steering predictive latents exploits biological motifs in pLM representations, yielding top-fitness variants in 83% of cases compared to designing with ESM2 alone.

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have emerged as the preferred method for this challenge, thanks to their ability to harness large sequence databases. Yet, their reliance on expansive sequence data and parameter sets limits their flexibility and practicality in real-world scenarios. Concurrently, the recent surge in computationally predicted protein structures unlocks new opportunities in protein representation learning. While promising, the computational burden carried by such complex data still hinders widely-adopted practical applications. To address these limitations, we introduce a novel framework that enhances protein language models by integrating protein structural data. Drawing from recent advances in graph transformers, our approach refines the self-attention mechanisms of pretrained language transformers by integrating structural information with structure extractor modules. This refined model, termed Protein Structure Transformer (PST), is further pretrained on a small protein structure database, using the same masked language modeling objective as traditional protein language models. Empirical evaluations of PST demonstrate its superior parameter efficiency relative to protein language models, despite being pretrained on a dataset comprising only 542K structures. Notably, PST consistently outperforms the state-of-the-art foundation model for protein sequences, ESM-2, setting a new benchmark in protein function prediction. Our findings underscore the potential of integrating structural information into protein language models, paving the way for more effective and efficient protein modeling Code and pretrained models are available at https://github.com/BorgwardtLab/PST.

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but lack the structural knowledge essential for many biological applications. To address this, we integrate structural insights from pre-trained protein graph neural networks (pGNNs) into pLMs through a latent-level contrastive learning task. This task aligns residue representations from pLMs with those from pGNNs across multiple proteins, enriching pLMs with inter-protein structural knowledge. Additionally, we incorporate a physical-level task that infuses intra-protein structural knowledge by optimizing pLMs to predict structural tokens. The proposed dual-task framework effectively incorporates both inter-protein and intra-protein structural knowledge into pLMs. Given the variability in the quality of protein structures in PDB, we further introduce a residue loss selection module, which uses a small model trained on high-quality structures to select reliable yet challenging residue losses for the pLM to learn. Applying our structure alignment method to the state-of-the-art ESM2 and AMPLIFY results in notable performance gains across a wide range of tasks, including a 12.7% increase in ESM2 contact prediction. The data, code, and resulting SaESM2 and SaAMPLIFY models will be released on Hugging Face.

Predicting protein function from sequence is a central challenge in computational biology. While existing methods rely heavily on structured ontologies or similarity-based techniques, they often lack the flexibility to express structure-free functional descriptions and novel biological functions. In this work, we introduce Prot2Text-V2, a novel multimodal sequence-to-text model that generates free-form natural language descriptions of protein function directly from amino acid sequences. Our method combines a protein language model as a sequence encoder (ESM-3B) and a decoder-only language model (LLaMA-3.1-8B-Instruct) through a lightweight nonlinear modality projector. A key innovation is our Hybrid Sequence-level Contrastive Alignment Learning (H-SCALE), which improves cross-modal learning by matching mean- and std-pooled protein embeddings with text representations via contrastive loss. After the alignment phase, we apply instruction-based fine-tuning using LoRA on the decoder to teach the model how to generate accurate protein function descriptions conditioned on the protein sequence. We train Prot2Text-V2 on about 250K curated entries from SwissProt and evaluate it under low-homology conditions, where test sequences have low similarity with training samples. Prot2Text-V2 consistently outperforms traditional and LLM-based baselines across various metrics.

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language Models (pLMs) aim to unlock insights from the vast space of unlabeled protein sequences by learning rich, semantic representations from primary sequences via masked language modeling. However, these models typically exhibit limited generative capacity. In this work, we introduce the Diffusion Sequence Model (DSM), a novel pLM trained with masked diffusion to enable both high-quality representation learning and generative protein design. DSM builds upon the ESM2 architecture by incorporating a masked forward diffusion process inspired by the LLaDA framework. After training, DSM is capable of generating diverse, biomimetic sequences that align with expected amino acid compositions, secondary structures, and predicted functions, even with 90\% token corruption. Furthermore, DSM's learned representations match or exceed those of similarly sized pLMs on downstream tasks. We also introduce DSM(ppi), a variant fine-tuned to generate protein binders by attending to target sequences. We demonstrate DSM(ppi)'s effectiveness on the challenging Bench-tested Binder Benchmark (BenchBB), where both DSM and DSM(ppi) produce candidates with superior predicted binding affinity compared to known binders. Our results establish masked diffusion as a powerful paradigm for unifying protein representation and generation in a single framework.

Protein language models (PLMs) encode rich biological information, yet their internal neuron representations are poorly understood. We introduce the first automated framework for labeling every neuron in a PLM with biologically grounded natural language descriptions. Unlike prior approaches relying on sparse autoencoders or manual annotation, our method scales to hundreds of thousands of neurons, revealing individual neurons are selectively sensitive to diverse biochemical and structural properties. We then develop a novel neuron activation-guided steering method to generate proteins with desired traits, enabling convergence to target biochemical properties like molecular weight and instability index as well as secondary and tertiary structural motifs, including alpha helices and canonical Zinc Fingers. We finally show that analysis of labeled neurons in different model sizes reveals PLM scaling laws and a structured neuron space distribution.

Learning effective protein representations is critical in a variety of tasks in biology such as predicting protein functions. Recent sequence representation learning methods based on Protein Language Models (PLMs) excel in sequence-based tasks, but their direct adaptation to tasks involving protein structures remains a challenge. In contrast, structure-based methods leverage 3D structural information with graph neural networks and geometric pre-training methods show potential in function prediction tasks, but still suffers from the limited number of available structures. To bridge this gap, our study undertakes a comprehensive exploration of joint protein representation learning by integrating a state-of-the-art PLM (ESM-2) with distinct structure encoders (GVP, GearNet, CDConv). We introduce three representation fusion strategies and explore different pre-training techniques. Our method achieves significant improvements over existing sequence- and structure-based methods, setting new state-of-the-art for function annotation. This study underscores several important design choices for fusing protein sequence and structure information. Our implementation is available at https://github.com/DeepGraphLearning/ESM-GearNet.

In recent years, protein-text models have gained significant attention for their potential in protein generation and understanding. Current approaches focus on integrating protein-related knowledge into large language models through continued pretraining and multi-modal alignment, enabling simultaneous comprehension of textual descriptions and protein sequences. Through a thorough analysis of existing model architectures and text-based protein understanding benchmarks, we identify significant data leakage issues present in current benchmarks. Moreover, conventional metrics derived from natural language processing fail to accurately assess the model's performance in this domain. To address these limitations, we reorganize existing datasets and introduce a novel evaluation framework based on biological entities. Motivated by our observation, we propose a retrieval-enhanced method, which significantly outperforms fine-tuned LLMs for protein-to-text generation and shows accuracy and efficiency in training-free scenarios. Our code and data can be seen at https://github.com/IDEA-XL/RAPM.

Multimodal protein language models (PLMs) integrate sequence and token-based structural information, serving as a powerful foundation for protein modeling, generation, and design. However, the reliance on tokenizing 3D structures into discrete tokens causes substantial loss of fidelity about fine-grained structural details and correlations. In this paper, we systematically elucidate the design space of multimodal PLMs to overcome their limitations. We identify tokenization loss and inaccurate structure token predictions by the PLMs as major bottlenecks. To address these, our proposed design space covers improved generative modeling, structure-aware architectures and representation learning, and data exploration. Our advancements approach finer-grained supervision, demonstrating that token-based multimodal PLMs can achieve robust structural modeling. The effective design methods dramatically improve the structure generation diversity, and notably, folding abilities of our 650M model by reducing the RMSD from 5.52 to 2.36 on PDB testset, even outperforming 3B baselines and on par with the specialized folding models.

Self-supervised training of language models (LMs) has seen great success for protein sequences in learning meaningful representations and for generative drug design. Most protein LMs are based on the Transformer architecture trained on individual proteins with short context lengths. Such protein LMs cannot extrapolate to longer proteins and protein complexes well. They also fail to account for the underlying biological mechanisms carried out by biomolecular interactions and dynamics i.e., proteins often interact with other proteins, molecules, and pathways in complex biological systems. In this work, we propose LC-PLM based on an alternative protein LM architecture, BiMamba-S, built off selective structured state-space models, to learn high-quality universal protein representations at the amino acid token level using masked language modeling. We also introduce its graph-contextual variant, LC-PLM-G, which contextualizes protein-protein interaction (PPI) graphs for a second stage of training. LC-PLM demonstrates favorable neural scaling laws, better length extrapolation capability, and a 7% to 34% improvement on protein downstream tasks than Transformer-based ESM-2. LC-PLM-G further trained within the context of PPI graphs shows promising results on protein structure and function prediction tasks. Our study demonstrates the benefit of increasing the context size with computationally efficient LM architecture (e.g. structured state space models) in learning universal protein representations and incorporating molecular interaction context contained in biological graphs.

Protein language models (PLMs) have emerged as powerful tools to detect complex patterns of protein sequences. However, the capability of PLMs to fully capture information on protein sequences might be limited by focusing on single pre-training tasks. Although adding data modalities or supervised objectives can improve the performance of PLMs, pre-training often remains focused on denoising corrupted sequences. To push the boundaries of PLMs, our research investigated a multi-task pre-training strategy. We developed Ankh3, a model jointly optimized on two objectives: masked language modeling with multiple masking probabilities and protein sequence completion relying only on protein sequences as input. This multi-task pre-training demonstrated that PLMs can learn richer and more generalizable representations solely from protein sequences. The results demonstrated improved performance in downstream tasks, such as secondary structure prediction, fluorescence, GB1 fitness, and contact prediction. The integration of multiple tasks gave the model a more comprehensive understanding of protein properties, leading to more robust and accurate predictions.

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in comprehending protein sequences remains an open question, largely due to the absence of datasets linking protein sequences to descriptive text. Researchers have then attempted to adapt LLMs for protein understanding by integrating a protein sequence encoder with a pre-trained LLM. However, this adaptation raises a fundamental question: "Can LLMs, originally designed for NLP, effectively comprehend protein sequences as a form of language?" Current datasets fall short in addressing this question due to the lack of a direct correlation between protein sequences and corresponding text descriptions, limiting the ability to train and evaluate LLMs for protein understanding effectively. To bridge this gap, we introduce ProteinLMDataset, a dataset specifically designed for further self-supervised pretraining and supervised fine-tuning (SFT) of LLMs to enhance their capability for protein sequence comprehension. Specifically, ProteinLMDataset includes 17.46 billion tokens for pretraining and 893,000 instructions for SFT. Additionally, we present ProteinLMBench, the first benchmark dataset consisting of 944 manually verified multiple-choice questions for assessing the protein understanding capabilities of LLMs. ProteinLMBench incorporates protein-related details and sequences in multiple languages, establishing a new standard for evaluating LLMs' abilities in protein comprehension. The large language model InternLM2-7B, pretrained and fine-tuned on the ProteinLMDataset, outperforms GPT-4 on ProteinLMBench, achieving the highest accuracy score. The dataset and the benchmark are available at https://huggingface.co/datasets/tsynbio/ProteinLMBench.

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.

While protein language models (pLMs) have transformed biological research, the scaling laws governing their improvement remain underexplored. By adapting methodologies from NLP scaling laws, we investigated the optimal ratio between model parameters and training tokens within a fixed compute budget. Our study reveals that pLM sizes scale sublinearly with compute budget, showing diminishing returns in performance as model size increases, and we identify a performance plateau in training loss comparable to the one found in relevant works in the field. Our findings suggest that widely-used pLMs might not be compute-optimal, indicating that larger models could achieve convergence more efficiently. Training a 35M model on a reduced token set, we attained perplexity results comparable to larger models like ESM-2 (15B) and xTrimoPGLM (100B) with a single dataset pass. This work paves the way towards more compute-efficient pLMs, democratizing their training and practical application in computational biology.

Current protein language models (PLMs) learn protein representations mainly based on their sequences, thereby well capturing co-evolutionary information, but they are unable to explicitly acquire protein functions, which is the end goal of protein representation learning. Fortunately, for many proteins, their textual property descriptions are available, where their various functions are also described. Motivated by this fact, we first build the ProtDescribe dataset to augment protein sequences with text descriptions of their functions and other important properties. Based on this dataset, we propose the ProtST framework to enhance Protein Sequence pre-training and understanding by biomedical Texts. During pre-training, we design three types of tasks, i.e., unimodal mask prediction, multimodal representation alignment and multimodal mask prediction, to enhance a PLM with protein property information with different granularities and, at the same time, preserve the PLM's original representation power. On downstream tasks, ProtST enables both supervised learning and zero-shot prediction. We verify the superiority of ProtST-induced PLMs over previous ones on diverse representation learning benchmarks. Under the zero-shot setting, we show the effectiveness of ProtST on zero-shot protein classification, and ProtST also enables functional protein retrieval from a large-scale database without any function annotation.

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent development of protein language models (pLMs) with supervised fine tuning provides a promising solution to this problem. However, the fine-tuned model is tailored for particular downstream prediction task, and achieving general-purpose protein understanding remains a challenge. In this paper, we introduce Structure-Enhanced Protein Instruction Tuning (SEPIT) framework to bridge this gap. Our approach integrates a noval structure-aware module into pLMs to inform them with structural knowledge, and then connects these enhanced pLMs to large language models (LLMs) to generate understanding of proteins. In this framework, we propose a novel two-stage instruction tuning pipeline that first establishes a basic understanding of proteins through caption-based instructions and then refines this understanding using a mixture of experts (MoEs) to learn more complex properties and functional information with the same amount of activated parameters. Moreover, we construct the largest and most comprehensive protein instruction dataset to date, which allows us to train and evaluate the general-purpose protein understanding model. Extensive experimental results on open-ended generation and closed-set answer tasks demonstrate the superior performance of SEPIT over both closed-source general LLMs and open-source LLMs trained with protein knowledge.

This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from evolutionary-scale protein sequences within a generative self-supervised discrete diffusion probabilistic framework, which generalizes language modeling for proteins in a principled way. After pre-training, DPLM exhibits the ability to generate structurally plausible, novel, and diverse protein sequences for unconditional generation. We further demonstrate the proposed diffusion generative pre-training makes DPLM possess a better understanding of proteins, making it a superior representation learner, which can be fine-tuned for various predictive tasks, comparing favorably to ESM2 (Lin et al., 2022). Moreover, DPLM can be tailored for various needs, which showcases its prowess of conditional generation in several ways: (1) conditioning on partial peptide sequences, e.g., generating scaffolds for functional motifs with high success rate; (2) incorporating other modalities as conditioner, e.g., structure-conditioned generation for inverse folding; and (3) steering sequence generation towards desired properties, e.g., satisfying specified secondary structures, through a plug-and-play classifier guidance. Code is released at https://github.com/bytedance/dplm.

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them struggle to handle protein understanding and generation tasks concurrently. We propose a unified protein language model, xTrimoPGLM, to address these two types of tasks simultaneously through an innovative pre-training framework. Our key technical contribution is an exploration of the compatibility and the potential for joint optimization of the two types of objectives, which has led to a strategy for training xTrimoPGLM at an unprecedented scale of 100 billion parameters and 1 trillion training tokens. Our extensive experiments reveal that 1) xTrimoPGLM significantly outperforms other advanced baselines in 18 protein understanding benchmarks across four categories. The model also facilitates an atomic-resolution view of protein structures, leading to an advanced 3D structural prediction model that surpasses existing language model-based tools. 2) xTrimoPGLM not only can generate de novo protein sequences following the principles of natural ones, but also can perform programmable generation after supervised fine-tuning (SFT) on curated sequences. These results highlight the substantial capability and versatility of xTrimoPGLM in understanding and generating protein sequences, contributing to the evolving landscape of foundation models in protein science.

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially reshape structural biology. However, the utility of the PLM module in AlphaFold, Evoformer, has not been explored beyond structure prediction. In this paper, we investigate the representation ability of three popular PLMs: ESM-1b (single sequence), MSA-Transformer (multiple sequence alignment) and Evoformer (structural), with a special focus on Evoformer. Specifically, we aim to answer the following key questions: (i) Does the Evoformer trained as part of AlphaFold produce representations amenable to predicting protein function? (ii) If yes, can Evoformer replace ESM-1b and MSA-Transformer? (ii) How much do these PLMs rely on evolution-related protein data? In this regard, are they complementary to each other? We compare these models by empirical study along with new insights and conclusions. All code and datasets for reproducibility are available at https://github.com/elttaes/Revisiting-PLMs.

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the generation of high-quality protein sequences. Specifically, we adopt a suite of pre-trained LLMs, including Mistral-7B1, Llama-2-7B2, Llama-3-8B3, and gemma-7B4, to produce valid protein sequences. All of these models are publicly available.5 Unlike previous work in this field, our approach utilizes a relatively small dataset comprising 42,000 distinct human protein sequences. We retrain these models to process protein-related data, ensuring the generation of biologically feasible protein structures. Our findings demonstrate that even with limited data, the adapted models exhibit efficiency comparable to established protein-focused models such as ProGen varieties, ProtGPT2, and ProLLaMA, which were trained on millions of protein sequences. To validate and quantify the performance of our models, we conduct comparative analyses employing standard metrics such as pLDDT, RMSD, TM-score, and REU. Furthermore, we commit to making the trained versions of all four models publicly available, fostering greater transparency and collaboration in the field of computational biology.

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional finetuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. We release the ProGen2 models and code at https://github.com/salesforce/progen.

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM that possesses bidirectional generation capabilities in both human and protein languages: (i) taking a protein sequence as input to predict its textual function description and (ii) using natural language to prompt protein sequence generation. To achieve this, we first pre-train an LLM on both protein and natural language corpora, enabling it to comprehend individual languages. Then supervised instruction tuning is employed to facilitate the alignment of these two distinct languages. Herein, we introduce a knowledge graph-based instruction generation framework to construct a high-quality instruction dataset, addressing annotation imbalance and instruction deficits in existing protein-text corpus. In particular, the instructions inherit the structural relations between proteins and function annotations in knowledge graphs, which empowers our model to engage in the causal modeling of protein functions, akin to the chain-of-thought processes in natural languages. Extensive experiments on bidirectional protein-text generation tasks show that InstructProtein outperforms state-of-the-art LLMs by large margins. Moreover, InstructProtein serves as a pioneering step towards text-based protein function prediction and sequence design, effectively bridging the gap between protein and human language understanding.

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential evolutionary knowledge from the universe of natural protein sequences, to acquire an immediate capability to design preferable protein sequences for given folds. We conduct a structural surgery on pLMs, where a lightweight structural adapter is implanted into pLMs and endows it with structural awareness. During inference, iterative refinement is performed to effectively optimize the generated protein sequences. Experiments show that LM-Design improves the state-of-the-art results by a large margin, leading to up to 4% to 12% accuracy gains in sequence recovery (e.g., 55.65%/56.63% on CATH 4.2/4.3 single-chain benchmarks, and >60% when designing protein complexes). We provide extensive and in-depth analyses, which verify that LM-Design can (1) indeed leverage both structural and sequential knowledge to accurately handle structurally non-deterministic regions, (2) benefit from scaling data and model size, and (3) generalize to other proteins (e.g., antibodies and de novo proteins)

In many scientific fields, large language models (LLMs) have revolutionized the way text and other modalities of data (e.g., molecules and proteins) are handled, achieving superior performance in various applications and augmenting the scientific discovery process. Nevertheless, previous surveys on scientific LLMs often concentrate on one or two fields or a single modality. In this paper, we aim to provide a more holistic view of the research landscape by unveiling cross-field and cross-modal connections between scientific LLMs regarding their architectures and pre-training techniques. To this end, we comprehensively survey over 260 scientific LLMs, discuss their commonalities and differences, as well as summarize pre-training datasets and evaluation tasks for each field and modality. Moreover, we investigate how LLMs have been deployed to benefit scientific discovery. Resources related to this survey are available at https://github.com/yuzhimanhua/Awesome-Scientific-Language-Models.

Protein representation learning is critical for numerous biological tasks. Recently, large transformer-based protein language models (pLMs) pretrained on large scale protein sequences have demonstrated significant success in sequence-based tasks. However, pLMs lack structural context. Conversely, graph neural networks (GNNs) designed to leverage 3D structural information have shown promising generalization in protein-related prediction tasks, but their effectiveness is often constrained by the scarcity of labeled structural data. Recognizing that sequence and structural representations are complementary perspectives of the same protein entity, we propose a multimodal bidirectional hierarchical fusion framework to effectively merge these modalities. Our framework employs attention and gating mechanisms to enable effective interaction between pLMs-generated sequential representations and GNN-extracted structural features, improving information exchange and enhancement across layers of the neural network. This bidirectional and hierarchical (Bi-Hierarchical) fusion approach leverages the strengths of both modalities to capture richer and more comprehensive protein representations. Based on the framework, we further introduce local Bi-Hierarchical Fusion with gating and global Bi-Hierarchical Fusion with multihead self-attention approaches. Our method demonstrates consistent improvements over strong baselines and existing fusion techniques in a variety of protein representation learning benchmarks, including enzyme EC classification, model quality assessment, protein-ligand binding affinity prediction, protein-protein binding site prediction, and B cell epitopes prediction. Our method establishes a new state-of-the-art for multimodal protein representation learning, emphasizing the efficacy of Bi-Hierarchical Fusion in bridging sequence and structural modalities.

With hundreds of thousands of language models available on Huggingface today, efficiently evaluating and utilizing these models across various downstream, tasks has become increasingly critical. Many existing methods repeatedly learn task-specific representations of Large Language Models (LLMs), which leads to inefficiencies in both time and computational resources. To address this, we propose EmbedLLM, a framework designed to learn compact vector representations, of LLMs that facilitate downstream applications involving many models, such as model routing. We introduce an encoder-decoder approach for learning such embeddings, along with a systematic framework to evaluate their effectiveness. Empirical results show that EmbedLLM outperforms prior methods in model routing both in accuracy and latency. Additionally, we demonstrate that our method can forecast a model's performance on multiple benchmarks, without incurring additional inference cost. Extensive probing experiments validate that the learned embeddings capture key model characteristics, e.g. whether the model is specialized for coding tasks, even without being explicitly trained on them. We open source our dataset, code and embedder to facilitate further research and application.

Large language models (LLMs) have demonstrated significant success in natural language processing (NLP) tasks and have shown promising results in other domains such as protein sequence generation. However, there remain salient differences between LLMs used for NLP, which effectively handle multiple tasks and are available in small sizes, and protein language models that are often specialized for specific tasks and only exist in larger sizes. In this work, we introduce two small protein language models, based on Llama-3-8B and Phi-3-mini, that are capable of both uncontrollable and controllable protein generation. For the uncontrollable generation task, our best model achieves an average pLDDT score of 69.75, demonstrating robust performance in generating viable protein structures. For the controllable generation task, in which the model generates proteins according to properties specified in the prompt, we achieve a remarkable average TM-Score of 0.84, indicating high structural similarity to target proteins. We chose 10 properties, including six classes of enzymes, to extend the capabilities of prior protein language models. Our approach utilizes the Low-Rank Adaptor (LoRA) technique, reducing trainable parameters to just 4% of the original model size, lowering computational requirements. By using a subset of the UniRef50 dataset and small models, we reduced the overall training time by 70% without compromising performance. Notably, Phi-3-mini reduced trainable parameters by 60%, decreasing training cost by 30% compared to Llama 3. Consequently, Phi-3 achieved a comparable TM-Score of 0.81, demonstrating that smaller models can match the performance of larger ones, like Llama 3. We also demonstrate the deployment of our models on the energy efficient ET-SoC-1 chip, significantly improving the TPS/W by a factor of 3.

Large language models (LLMs) have revolutionized natural language processing by achieving state-of-the-art performance across various tasks. Recently, their effectiveness as embedding models has gained attention, marking a paradigm shift from traditional encoder-only models like ELMo and BERT to decoder-only, large-scale LLMs such as GPT, LLaMA, and Mistral. This survey provides an in-depth overview of this transition, beginning with foundational techniques before the LLM era, followed by LLM-based embedding models through two main strategies to derive embeddings from LLMs. 1) Direct prompting: We mainly discuss the prompt designs and the underlying rationale for deriving competitive embeddings. 2) Data-centric tuning: We cover extensive aspects that affect tuning an embedding model, including model architecture, training objectives, data constructions, etc. Upon the above, we also cover advanced methods, such as handling longer texts, and multilingual and cross-modal data. Furthermore, we discuss factors affecting choices of embedding models, such as performance/efficiency comparisons, dense vs sparse embeddings, pooling strategies, and scaling law. Lastly, the survey highlights the limitations and challenges in adapting LLMs for embeddings, including cross-task embedding quality, trade-offs between efficiency and accuracy, low-resource, long-context, data bias, robustness, etc. This survey serves as a valuable resource for researchers and practitioners by synthesizing current advancements, highlighting key challenges, and offering a comprehensive framework for future work aimed at enhancing the effectiveness and efficiency of LLMs as embedding models.

Motivation: Proteins are of great significance in living organisms. However, understanding their functions encounters numerous challenges, such as insufficient integration of multimodal information, a large number of training parameters, limited flexibility of classification-based methods, and the lack of systematic evaluation metrics for protein Q&A systems. To tackle these issues, we propose the Prot2Chat framework. Results: We modified ProteinMPNN to encode protein sequence and structural information in a unified way. We used a large language model (LLM) to encode questions into vectors and developed a protein-text adapter to compress protein information into virtual tokens based on these vectors, achieving the early fusion of text and protein information. Finally, the same LLM reads the virtual tokens and the questions to generate answers. To optimize training efficiency, we froze the encoder and employed Low-Rank Adaptation (LoRA) techniques for the LLM. Experiments on two datasets show that both automated metrics and expert evaluations demonstrate the superior performance of our model, and zero-shot prediction results highlight its generalization ability. The models and codes are available at https://github.com/ wangzc1233/Prot2Chat. Contact: zqcao@suda.edu.cn or wangzc025@163.com Key words: Protein Q&A, Early-Fusion, LLM

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates a multimodal approach to simultaneously model, understand, and generate both sequences and structures. However, existing methods typically use separate models for each modality, limiting their ability to capture the intricate relationships between sequence and structure. This results in suboptimal performance in tasks that requires joint understanding and generation of both modalities. In this paper, we introduce DPLM-2, a multimodal protein foundation model that extends discrete diffusion protein language model (DPLM) to accommodate both sequences and structures. To enable structural learning with the language model, 3D coordinates are converted to discrete tokens using a lookup-free quantization-based tokenizer. By training on both experimental and high-quality synthetic structures, DPLM-2 learns the joint distribution of sequence and structure, as well as their marginals and conditionals. We also implement an efficient warm-up strategy to exploit the connection between large-scale evolutionary data and structural inductive biases from pre-trained sequence-based protein language models. Empirical evaluation shows that DPLM-2 can simultaneously generate highly compatible amino acid sequences and their corresponding 3D structures eliminating the need for a two-stage generation approach. Moreover, DPLM-2 demonstrates competitive performance in various conditional generation tasks, including folding, inverse folding, and scaffolding with multimodal motif inputs, as well as providing structure-aware representations for predictive tasks.

The complex nature of big biological systems pushed some scientists to classify its understanding under the inconceivable missions. Different leveled challenges complicated this task, one of is the prediction of a protein's function. In recent years, significant progress has been made in this field through the development of various machine learning approaches. However, most existing methods formulate the task as a multi-classification problem, i.e assigning predefined labels to proteins. In this work, we propose a novel approach, Prot2Text, which predicts a protein function's in a free text style, moving beyond the conventional binary or categorical classifications. By combining Graph Neural Networks(GNNs) and Large Language Models(LLMs), in an encoder-decoder framework, our model effectively integrates diverse data types including proteins' sequences, structures, and textual annotations. This multimodal approach allows for a holistic representation of proteins' functions, enabling the generation of detailed and accurate descriptions. To evaluate our model, we extracted a multimodal protein dataset from SwissProt, and demonstrate empirically the effectiveness of Prot2Text. These results highlight the transformative impact of multimodal models, specifically the fusion of GNNs and LLMs, empowering researchers with powerful tools for more accurate prediction of proteins' functions. The code, the models and a demo will be publicly released.

Large decoder-only language models (LLMs) have achieved remarkable success in generation and reasoning tasks, where they generate text responses given instructions. However, many applications, e.g., retrieval augmented generation (RAG), still rely on separate embedding models to generate text embeddings, which can complicate the system and introduce discrepancies in understanding of the query between the embedding model and LLMs. To address this limitation, we propose a simple self-supervised approach, Generative Embedding large language Model (GEM), that enables any large decoder-only LLM to generate high-quality text embeddings while maintaining its original text generation and reasoning capabilities. Our method inserts new special token(s) into a text body, and generates summarization embedding of the text by manipulating the attention mask. This method could be easily integrated into post-training or fine tuning stages of any existing LLMs. We demonstrate the effectiveness of our approach by applying it to two popular LLM families, ranging from 1B to 8B parameters, and evaluating the transformed models on both text embedding benchmarks (MTEB) and NLP benchmarks (MMLU). The results show that our proposed method significantly improves the original LLMs on MTEB while having a minimal impact on MMLU. Our strong results indicate that our approach can empower LLMs with state-of-the-art text embedding capabilities while maintaining their original NLP performance

Large Language Models (LLMs), including GPT-x and LLaMA2, have achieved remarkable performance in multiple Natural Language Processing (NLP) tasks. Under the premise that protein sequences constitute the protein language, Protein Large Language Models (ProLLMs) trained on protein corpora excel at de novo protein sequence generation. However, as of now, unlike LLMs in NLP, no ProLLM is capable of multiple tasks in the Protein Language Processing (PLP) field. This prompts us to delineate the inherent limitations in current ProLLMs: (i) the lack of natural language capabilities, (ii) insufficient instruction understanding, and (iii) high training resource demands. To address these challenges, we introduce a training framework to transform any general LLM into a ProLLM capable of handling multiple PLP tasks. Specifically, our framework utilizes low-rank adaptation and employs a two-stage training approach, and it is distinguished by its universality, low overhead, and scalability. Through training under this framework, we propose the ProLLaMA model, the first known ProLLM to handle multiple PLP tasks simultaneously. Experiments show that ProLLaMA achieves state-of-the-art results in the unconditional protein sequence generation task. In the controllable protein sequence generation task, ProLLaMA can design novel proteins with desired functionalities. In the protein property prediction task, ProLLaMA achieves nearly 100\% accuracy across many categories. The latter two tasks are beyond the reach of other ProLLMs. Code is available at https://github.com/Lyu6PosHao/ProLLaMA.

Language Models (LMs) have greatly influenced diverse domains. However, their inherent limitation in comprehending 3D molecular structures has considerably constrained their potential in the biomolecular domain. To bridge this gap, we focus on 3D molecule-text interpretation, and propose 3D-MoLM: 3D-Molecular Language Modeling. Specifically, 3D-MoLM enables an LM to interpret and analyze 3D molecules by equipping the LM with a 3D molecular encoder. This integration is achieved by a 3D molecule-text projector, bridging the 3D molecular encoder's representation space and the LM's input space. Moreover, to enhance 3D-MoLM's ability of cross-modal molecular understanding and instruction following, we meticulously curated a 3D molecule-centric instruction tuning dataset -- 3D-MoIT. Through 3D molecule-text alignment and 3D molecule-centric instruction tuning, 3D-MoLM establishes an integration of 3D molecular encoder and LM. It significantly surpasses existing baselines on downstream tasks, including molecule-text retrieval, molecule captioning, and more challenging open-text molecular QA tasks, especially focusing on 3D-dependent properties.

Efficient molecular modeling and design are crucial for the discovery and exploration of novel molecules, and the incorporation of deep learning methods has revolutionized this field. In particular, large language models (LLMs) offer a fresh approach to tackle scientific problems from a natural language processing (NLP) perspective, introducing a research paradigm called scientific language modeling (SLM). However, two key issues remain: how to quantify the match between model and data modalities and how to identify the knowledge-learning preferences of models. To address these challenges, we propose a multi-modal benchmark, named ChEBI-20-MM, and perform 1263 experiments to assess the model's compatibility with data modalities and knowledge acquisition. Through the modal transition probability matrix, we provide insights into the most suitable modalities for tasks. Furthermore, we introduce a statistically interpretable approach to discover context-specific knowledge mapping by localized feature filtering. Our pioneering analysis offers an exploration of the learning mechanism and paves the way for advancing SLM in molecular science.

Decoder-only large language models (LLMs) are increasingly used to build embedding models that effectively encode the semantic information of natural language texts into dense vector representations for various embedding tasks. However, many existing methods primarily focus on removing the causal attention mask in LLMs to enable bidirectional attention, potentially undermining the model's ability to extract semantic information acquired during pretraining. Additionally, leading unidirectional approaches often rely on extra input text to overcome the inherent limitations of causal attention, inevitably increasing computational costs. In this work, we propose Causal2Vec, a general-purpose embedding model tailored to enhance the performance of decoder-only LLMs without altering their original architectures or introducing significant computational overhead. Specifically, we first employ a lightweight BERT-style model to pre-encode the input text into a single Contextual token, which is then prepended to the LLM's input sequence, allowing each token to capture contextualized information even without attending to future tokens. Furthermore, to mitigate the recency bias introduced by last-token pooling and help LLMs better leverage the semantic information encoded in the Contextual token, we concatenate the last hidden states of Contextual and EOS tokens as the final text embedding. In practice, Causal2Vec achieves state-of-the-art performance on the Massive Text Embeddings Benchmark (MTEB) among models trained solely on publicly available retrieval datasets, while reducing the required sequence length by up to 85% and inference time by up to 82% compared to best-performing methods.

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling.

Word embeddings and language models have transformed natural language processing (NLP) by facilitating the representation of linguistic elements in continuous vector spaces. This review visits foundational concepts such as the distributional hypothesis and contextual similarity, tracing the evolution from sparse representations like one-hot encoding to dense embeddings including Word2Vec, GloVe, and fastText. We examine both static and contextualized embeddings, underscoring advancements in models such as ELMo, BERT, and GPT and their adaptations for cross-lingual and personalized applications. The discussion extends to sentence and document embeddings, covering aggregation methods and generative topic models, along with the application of embeddings in multimodal domains, including vision, robotics, and cognitive science. Advanced topics such as model compression, interpretability, numerical encoding, and bias mitigation are analyzed, addressing both technical challenges and ethical implications. Additionally, we identify future research directions, emphasizing the need for scalable training techniques, enhanced interpretability, and robust grounding in non-textual modalities. By synthesizing current methodologies and emerging trends, this survey offers researchers and practitioners an in-depth resource to push the boundaries of embedding-based language models.

Scientific Large Language Models (Sci-LLMs) have emerged as a promising frontier for accelerating biological discovery. However, these models face a fundamental challenge when processing raw biomolecular sequences: the tokenization dilemma. Whether treating sequences as a specialized language, risking the loss of functional motif information, or as a separate modality, introducing formidable alignment challenges, current strategies fundamentally limit their reasoning capacity. We challenge this sequence-centric paradigm by positing that a more effective strategy is to provide Sci-LLMs with high-level structured context derived from established bioinformatics tools, thereby bypassing the need to interpret low-level noisy sequence data directly. Through a systematic comparison of leading Sci-LLMs on biological reasoning tasks, we tested three input modes: sequence-only, context-only, and a combination of both. Our findings are striking: the context-only approach consistently and substantially outperforms all other modes. Even more revealing, the inclusion of the raw sequence alongside its high-level context consistently degrades performance, indicating that raw sequences act as informational noise, even for models with specialized tokenization schemes. These results suggest that the primary strength of existing Sci-LLMs lies not in their nascent ability to interpret biomolecular syntax from scratch, but in their profound capacity for reasoning over structured, human-readable knowledge. Therefore, we argue for reframing Sci-LLMs not as sequence decoders, but as powerful reasoning engines over expert knowledge. This work lays the foundation for a new class of hybrid scientific AI agents, repositioning the developmental focus from direct sequence interpretation towards high-level knowledge synthesis. The code is available at https://github.com/opendatalab-raiser/CoKE.

As retrieval-augmented generation prevails in large language models, embedding models are becoming increasingly crucial. Despite the growing number of general embedding models, prior work often overlooks the critical role of training data quality. In this work, we introduce KaLM-Embedding, a general multilingual embedding model that leverages a large quantity of cleaner, more diverse, and domain-specific training data. Our model has been trained with key techniques proven to enhance performance: (1) persona-based synthetic data to create diversified examples distilled from LLMs, (2) ranking consistency filtering to remove less informative samples, and (3) semi-homogeneous task batch sampling to improve training efficacy. Departing from traditional BERT-like architectures, we adopt Qwen2-0.5B as the pre-trained model, facilitating the adaptation of auto-regressive language models for general embedding tasks. Extensive evaluations of the MTEB benchmark across multiple languages show that our model outperforms others of comparable size, setting a new standard for multilingual embedding models with <1B parameters.

Large language models (LLMs) with decoder-only architectures demonstrate remarkable in-context learning (ICL) capabilities. This feature enables them to effectively handle both familiar and novel tasks by utilizing examples provided within their input context. Recognizing the potential of this capability, we propose leveraging the ICL feature in LLMs to enhance the process of text embedding generation. To this end, we introduce a novel model bge-en-icl, which employs few-shot examples to produce high-quality text embeddings. Our approach integrates task-related examples directly into the query side, resulting in significant improvements across various tasks. Additionally, we have investigated how to effectively utilize LLMs as embedding models, including various attention mechanisms, pooling methods, etc. Our findings suggest that retaining the original framework often yields the best results, underscoring that simplicity is best. Experimental results on the MTEB and AIR-Bench benchmarks demonstrate that our approach sets new state-of-the-art (SOTA) performance. Our model, code and dataset are freely available at https://github.com/FlagOpen/FlagEmbedding .

Text embeddings have attracted growing interest due to their effectiveness across a wide range of natural language processing (NLP) tasks, such as retrieval, classification, clustering, bitext mining, and summarization. With the emergence of pretrained language models (PLMs), general-purpose text embeddings (GPTE) have gained significant traction for their ability to produce rich, transferable representations. The general architecture of GPTE typically leverages PLMs to derive dense text representations, which are then optimized through contrastive learning on large-scale pairwise datasets. In this survey, we provide a comprehensive overview of GPTE in the era of PLMs, focusing on the roles PLMs play in driving its development. We first examine the fundamental architecture and describe the basic roles of PLMs in GPTE, i.e., embedding extraction, expressivity enhancement, training strategies, learning objectives, and data construction. Then, we describe advanced roles enabled by PLMs, such as multilingual support, multimodal integration, code understanding, and scenario-specific adaptation. Finally, we highlight potential future research directions that move beyond traditional improvement goals, including ranking integration, safety considerations, bias mitigation, structural information incorporation, and the cognitive extension of embeddings. This survey aims to serve as a valuable reference for both newcomers and established researchers seeking to understand the current state and future potential of GPTE.

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated remarkable success in predicting protein structure and function, their application to sequence-based PPI binding affinity prediction remains relatively underexplored. This gap is often attributed to the scarcity of high-quality, rigorously refined datasets and the reliance on simple strategies for concatenating protein representations. In this work, we address these limitations. First, we introduce a meticulously curated version of the PPB-Affinity dataset of a total of 8,207 unique protein-protein interaction entries, by resolving annotation inconsistencies and duplicate entries for multi-chain protein interactions. This dataset incorporates a stringent, less than or equal to 30%, sequence identity threshold to ensure robust splitting into training, validation, and test sets, minimizing data leakage. Second, we propose and systematically evaluate four architectures for adapting PLMs to PPI binding affinity prediction: embeddings concatenation (EC), sequences concatenation (SC), hierarchical pooling (HP), and pooled attention addition (PAD). These architectures were assessed using two training methods: full fine-tuning and a lightweight approach employing ConvBERT heads over frozen PLM features. Our comprehensive experiments across multiple leading PLMs (ProtT5, ESM2, Ankh, Ankh2, and ESM3) demonstrated that the HP and PAD architectures consistently outperform conventional concatenation methods, achieving up to 12% increase in terms of Spearman correlation. These results highlight the necessity of sophisticated architectural designs to fully exploit the capabilities of PLMs for nuanced PPI binding affinity prediction.

Language Models (LMs) excel in natural language processing tasks for English but show reduced performance in most other languages. This problem is commonly tackled by continually pre-training and fine-tuning these models for said languages. A significant issue in this process is the limited vocabulary coverage in the original model's tokenizer, leading to inadequate representation of new languages and necessitating an expansion of the tokenizer. The initialization of the embeddings corresponding to new vocabulary items presents a further challenge. Current strategies require cross-lingual embeddings and lack a solid theoretical foundation as well as comparisons with strong baselines. In this paper, we first establish theoretically that initializing within the convex hull of existing embeddings is a good initialization, followed by a novel but simple approach, Constrained Word2Vec (CW2V), which does not require cross-lingual embeddings. Our study evaluates different initialization methods for expanding RoBERTa and LLaMA 2 across four languages and five tasks. The results show that CW2V performs equally well or even better than more advanced techniques. Additionally, simpler approaches like multivariate initialization perform on par with these advanced methods indicating that efficient large-scale multilingual continued pretraining can be achieved even with simpler initialization methods.

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel fine-tuning approach to improve the performance of PLMs with experimental maps of variant effects from Deep Mutational Scanning (DMS) assays using a Normalised Log-odds Ratio (NLR) head. We find consistent improvements in a held-out protein test set, and on independent DMS and clinical variant annotation benchmarks from ProteinGym and ClinVar. These findings demonstrate that DMS is a promising source of sequence diversity and supervised training data for improving the performance of PLMs for variant effect prediction.

As opposed to scaling-up protein language models (PLMs), we seek improving performance via protein-specific optimization. Although the proportionality between the language model size and the richness of its learned representations is validated, we prioritize accessibility and pursue a path of data-efficient, cost-reduced, and knowledge-guided optimization. Through over twenty experiments ranging from masking, architecture, and pre-training data, we derive insights from protein-specific experimentation into building a model that interprets the language of life, optimally. We present Ankh, the first general-purpose PLM trained on Google's TPU-v4 surpassing the state-of-the-art performance with fewer parameters (<10% for pre-training, <7% for inference, and <30% for the embedding dimension). We provide a representative range of structure and function benchmarks where Ankh excels. We further provide a protein variant generation analysis on High-N and One-N input data scales where Ankh succeeds in learning protein evolutionary conservation-mutation trends and introducing functional diversity while retaining key structural-functional characteristics. We dedicate our work to promoting accessibility to research innovation via attainable resources.

Text embedding has become a foundational technology in natural language processing (NLP) during the deep learning era, driving advancements across a wide array of downstream tasks. While many natural language understanding challenges can now be modeled using generative paradigms and leverage the robust generative and comprehension capabilities of large language models (LLMs), numerous practical applications, such as semantic matching, clustering, and information retrieval, continue to rely on text embeddings for their efficiency and effectiveness. In this survey, we categorize the interplay between LLMs and text embeddings into three overarching themes: (1) LLM-augmented text embedding, enhancing traditional embedding methods with LLMs; (2) LLMs as text embedders, utilizing their innate capabilities for embedding generation; and (3) Text embedding understanding with LLMs, leveraging LLMs to analyze and interpret embeddings. By organizing these efforts based on interaction patterns rather than specific downstream applications, we offer a novel and systematic overview of contributions from various research and application domains in the era of LLMs. Furthermore, we highlight the unresolved challenges that persisted in the pre-LLM era with pre-trained language models (PLMs) and explore the emerging obstacles brought forth by LLMs. Building on this analysis, we outline prospective directions for the evolution of text embedding, addressing both theoretical and practical opportunities in the rapidly advancing landscape of NLP.

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional architectures in a causal multi-headed graph mechanism, to realize a generative pretrained model. The model is applied to predict secondary structure content (per-residue level and overall content), protein solubility, and sequencing tasks. Further trained on inverse tasks, the model is rendered capable of designing proteins with these properties as target features. The model is formulated as a general framework, completely prompt-based, and can be adapted for a variety of downstream tasks. We find that adding additional tasks yields emergent synergies that the model exploits in improving overall performance, beyond what would be possible by training a model on each dataset alone. Case studies are presented to validate the method, yielding protein designs specifically focused on structural proteins, but also exploring the applicability in the design of soluble, antimicrobial biomaterials. While our model is trained to ultimately perform 8 distinct tasks, with available datasets it can be extended to solve additional problems. In a broader sense, this work illustrates a form of multiscale modeling that relates a set of ultimate building blocks (here, byte-level utf8 characters) to complex output. This materiomic scheme captures complex emergent relationships between universal building block and resulting properties via a synergizing learning capacity to express a set of potentialities embedded in the knowledge used in training, via the interplay of universality and diversity.

We introduce EmbeddingGemma, a new lightweight, open text embedding model based on the Gemma 3 language model family. Our innovative training recipe strategically captures knowledge from larger models via encoder-decoder initialization and geometric embedding distillation. We improve model robustness and expressiveness with a spread-out regularizer, and ensure generalizability by merging checkpoints from varied, optimized mixtures. Evaluated on the Massive Text Embedding Benchmark (MTEB) across multilingual, English, and code domains, EmbeddingGemma (300M) achieves state-of-the-art results. Notably, it outperforms prior top models, both proprietary and open, with fewer than 500M parameters, and provides performance comparable to models double its size, offering an exceptional performance-to-cost ratio. Remarkably, this lead persists when quantizing model weights or truncating embedding outputs. This makes EmbeddingGemma particularly well-suited for low-latency and high-throughput use cases such as on-device applications. We provide ablation studies exploring our key design choices. We release EmbeddingGemma to the community to promote further research.

In the large language model (LLM) revolution, embedding is a key component of various systems. For example, it is used to retrieve knowledge or memories for LLMs, to build content moderation filters, etc. As such cases span from English to other natural or programming languages, from retrieval to classification and beyond, it is desirable to build a unified embedding model rather than dedicated ones for each scenario. In this work, we make an initial step towards this goal, demonstrating that multiple languages (both natural and programming) pre-trained transformer decoders can embed universally when finetuned on limited English data. We provide a comprehensive practice with thorough evaluations. On English MTEB, our models achieve competitive performance on different embedding tasks by minimal training data. On other benchmarks, such as multilingual classification and code search, our models (without any supervision) perform comparably to, or even surpass heavily supervised baselines and/or APIs. These results provide evidence of a promising path towards building powerful unified embedders that can be applied across tasks and languages.

Large language models (LLMs) have garnered unprecedented advancements across diverse fields, ranging from natural language processing to computer vision and beyond. The prowess of LLMs is underpinned by their substantial model size, extensive and diverse datasets, and the vast computational power harnessed during training, all of which contribute to the emergent abilities of LLMs (e.g., in-context learning) that are not present in small models. Within this context, the mixture of experts (MoE) has emerged as an effective method for substantially scaling up model capacity with minimal computation overhead, gaining significant attention from academia and industry. Despite its growing prevalence, there lacks a systematic and comprehensive review of the literature on MoE. This survey seeks to bridge that gap, serving as an essential resource for researchers delving into the intricacies of MoE. We first briefly introduce the structure of the MoE layer, followed by proposing a new taxonomy of MoE. Next, we overview the core designs for various MoE models including both algorithmic and systemic aspects, alongside collections of available open-source implementations, hyperparameter configurations and empirical evaluations. Furthermore, we delineate the multifaceted applications of MoE in practice, and outline some potential directions for future research. To facilitate ongoing updates and the sharing of cutting-edge developments in MoE research, we have established a resource repository accessible at https://github.com/withinmiaov/A-Survey-on-Mixture-of-Experts.

Large Language Models (LLMs) have demonstrated remarkable proficiency in understanding and generating natural language. However, their capabilities wane in highly specialized domains underrepresented in the pretraining corpus, such as physical and biomedical sciences. This work explores how to repurpose general LLMs into effective task solvers for specialized domains. We introduce a novel, model-agnostic framework for learning custom input tags, which are parameterized as continuous vectors appended to the LLM's embedding layer, to condition the LLM. We design two types of input tags: domain tags are used to delimit specialized representations (e.g., chemical formulas) and provide domain-relevant context; function tags are used to represent specific functions (e.g., predicting molecular properties) and compress function-solving instructions. We develop a three-stage protocol to learn these tags using auxiliary data and domain knowledge. By explicitly disentangling task domains from task functions, our method enables zero-shot generalization to unseen problems through diverse combinations of the input tags. It also boosts LLM's performance in various specialized domains, such as predicting protein or chemical properties and modeling drug-target interactions, outperforming expert models tailored to these tasks.

Common approaches rely on fixed-length embedding vectors from language models as sentence embeddings for downstream tasks such as semantic textual similarity (STS). Such methods are limited in their flexibility due to unknown computational constraints and budgets across various applications. Matryoshka Representation Learning (MRL) (Kusupati et al., 2022) encodes information at finer granularities, i.e., with lower embedding dimensions, to adaptively accommodate ad hoc tasks. Similar accuracy can be achieved with a smaller embedding size, leading to speedups in downstream tasks. Despite its improved efficiency, MRL still requires traversing all Transformer layers before obtaining the embedding, which remains the dominant factor in time and memory consumption. This prompts consideration of whether the fixed number of Transformer layers affects representation quality and whether using intermediate layers for sentence representation is feasible. In this paper, we introduce a novel sentence embedding model called Two-dimensional Matryoshka Sentence Embedding (2DMSE). It supports elastic settings for both embedding sizes and Transformer layers, offering greater flexibility and efficiency than MRL. We conduct extensive experiments on STS tasks and downstream applications. The experimental results demonstrate the effectiveness of our proposed model in dynamically supporting different embedding sizes and Transformer layers, allowing it to be highly adaptable to various scenarios.

Intermediate task transfer learning can greatly improve model performance. If, for example, one has little training data for emotion detection, first fine-tuning a language model on a sentiment classification dataset may improve performance strongly. But which task to choose for transfer learning? Prior methods producing useful task rankings are infeasible for large source pools, as they require forward passes through all source language models. We overcome this by introducing Embedding Space Maps (ESMs), light-weight neural networks that approximate the effect of fine-tuning a language model. We conduct the largest study on NLP task transferability and task selection with 12k source-target pairs. We find that applying ESMs on a prior method reduces execution time and disk space usage by factors of 10 and 278, respectively, while retaining high selection performance (avg. regret@5 score of 2.95).

English-centric large language models (LLMs) often show strong multilingual capabilities. However, the multilingual performance of these models remains unclear and is not thoroughly evaluated for many languages. Most benchmarks for multilinguality focus on classic NLP tasks, or cover a minimal number of languages. We introduce MEXA, a method for assessing the multilingual capabilities of pre-trained English-centric LLMs using parallel sentences, which are available for more languages than existing downstream tasks. MEXA leverages the fact that English-centric LLMs use English as a kind of pivot language in their intermediate layers. It computes the alignment between English and non-English languages using parallel sentences to evaluate the transfer of language understanding from English to other languages. This alignment can be used to estimate model performance in other languages. We conduct studies using various parallel datasets (FLORES-200 and Bible), models (Llama family, Gemma family, Mistral, and OLMo), and established downstream tasks (Belebele, m-MMLU, and m-ARC). We explore different methods to compute embeddings in decoder-only models. Our results show that MEXA, in its default settings, achieves a statistically significant average Pearson correlation of 0.90 with three established downstream tasks across nine models and two parallel datasets. This suggests that MEXA is a reliable method for estimating the multilingual capabilities of English-centric LLMs, providing a clearer understanding of their multilingual potential and the inner workings of LLMs. Leaderboard: https://huggingface.co/spaces/cis-lmu/Mexa, Code: https://github.com/cisnlp/Mexa.

In this paper, we propose KaLM-Embedding-V2, a versatile and compact embedding model, which achieves impressive performance in general-purpose text embedding tasks by leveraging superior training techniques and data. Our key innovations include: (1) To better align the architecture with representation learning, we remove the causal attention mask and adopt a fully bidirectional transformer with simple yet effective mean-pooling to produce fixed-length embeddings; (2) We employ a multi-stage training pipeline: (i) pre-training on large-scale weakly supervised open-source corpora; (ii) fine-tuning on high-quality retrieval and non-retrieval datasets; and (iii) model-soup parameter averaging for robust generalization. Besides, we introduce a focal-style reweighting mechanism that concentrates learning on difficult samples and an online hard-negative mixing strategy to continuously enrich hard negatives without expensive offline mining; (3) We collect over 20 categories of data for pre-training and 100 categories of data for fine-tuning, to boost both the performance and generalization of the embedding model. Extensive evaluations on the Massive Text Embedding Benchmark (MTEB) Chinese and English show that our model significantly outperforms others of comparable size, and competes with 3x, 14x, 18x, and 26x larger embedding models, setting a new standard for a versatile and compact embedding model with less than 1B parameters.

Recently, there has been a significant upsurge of interest in leveraging large language models (LLMs) to assist scientific discovery. However, most LLMs only focus on general science, while they lack domain-specific knowledge, such as chemical molecules and amino acid sequences. To bridge these gaps, we introduce SciDFM, a mixture-of-experts LLM, which is trained from scratch and is able to conduct college-level scientific reasoning and understand molecules and amino acid sequences. We collect a large-scale training corpus containing numerous scientific papers and books from different disciplines as well as data from domain-specific databases. We further fine-tune the pre-trained model on lots of instruction data to improve performances on downstream benchmarks. From experiment results, we show that SciDFM achieves strong performance on general scientific benchmarks such as SciEval and SciQ, and it reaches a SOTA performance on domain-specific benchmarks among models of similar size. We further analyze the expert layers and show that the results of expert selection vary with data from different disciplines. To benefit the broader research community, we open-source SciDFM at https://huggingface.co/OpenDFM/SciDFM-MoE-A5.6B-v1.0.

The integration of molecule and language has garnered increasing attention in molecular science. Recent advancements in Language Models (LMs) have demonstrated potential for the comprehensive modeling of molecule and language. However, existing works exhibit notable limitations. Most existing works overlook the modeling of 3D information, which is crucial for understanding molecular structures and also functions. While some attempts have been made to leverage external structure encoding modules to inject the 3D molecular information into LMs, there exist obvious difficulties that hinder the integration of molecular structure and language text, such as modality alignment and separate tuning. To bridge this gap, we propose 3D-MolT5, a unified framework designed to model both 1D molecular sequence and 3D molecular structure. The key innovation lies in our methodology for mapping fine-grained 3D substructure representations (based on 3D molecular fingerprints) to a specialized 3D token vocabulary for 3D-MolT5. This 3D structure token vocabulary enables the seamless combination of 1D sequence and 3D structure representations in a tokenized format, allowing 3D-MolT5 to encode molecular sequence (SELFIES), molecular structure, and text sequences within a unified architecture. Alongside, we further introduce 1D and 3D joint pre-training to enhance the model's comprehension of these diverse modalities in a joint representation space and better generalize to various tasks for our foundation model. Through instruction tuning on multiple downstream datasets, our proposed 3D-MolT5 shows superior performance than existing methods in molecular property prediction, molecule captioning, and text-based molecule generation tasks. Our code will be available on GitHub soon.

Language models (LMs) automatically learn word embeddings during pre-training on language corpora. Although word embeddings are usually interpreted as feature vectors for individual words, their roles in language model generation remain underexplored. In this work, we theoretically and empirically revisit output word embeddings and find that their linear transformations are equivalent to steering language model generation styles. We name such steers LM-Steers and find them existing in LMs of all sizes. It requires learning parameters equal to 0.2% of the original LMs' size for steering each style. On tasks such as language model detoxification and sentiment control, LM-Steers can achieve comparable or superior performance compared with state-of-the-art controlled generation methods while maintaining a better balance with generation quality. The learned LM-Steer serves as a lens in text styles: it reveals that word embeddings are interpretable when associated with language model generations and can highlight text spans that most indicate the style differences. An LM-Steer is transferrable between different language models by an explicit form calculation. One can also continuously steer LMs simply by scaling the LM-Steer or compose multiple LM-Steers by adding their transformations. Our codes are publicly available at https://github.com/Glaciohound/LM-Steer.

In recent years, large language models (LLMs) have achieved state-of-the-art results in various biological sequence analysis tasks, such as sequence classification, structure prediction, and function prediction. Similar to advancements in AI for other scientific fields, deeper research into biological LLMs has begun to focus on using these models to rediscover important existing biological laws or uncover entirely new patterns in biological sequences.This study leverages GPT-like LLMs to utilize language transfer capabilities to rediscover the genetic code rules of the central dogma. In our experimental design, we transformed the central dogma into a binary classification problem of aligning DNA sequences with protein sequences, where positive examples are matching DNA and protein sequences, and negative examples are non-matching pairs.We first trained a GPT-2 model from scratch using a dataset comprising protein sequences, DNA sequences, and sequences from languages such as English and Chinese. Subsequently, we fine-tuned the model using the English similarity judgment dataset from PAWS-X. When tested on a dataset for DNA and protein sequence alignment judgment, the fine-tuned model achieved a classification accuracy of 76%. The study also analyzed factors contributing to this zero-shot capability, including model training stability and types of training data.This research demonstrates that LLMs can, through the transfer of natural language capabilities and solely relying on the analysis of sequences themselves, rediscover the central dogma without prior knowledge of it. This study opens a new door for AI-driven biological research.

The diverse nature of protein prediction tasks has traditionally necessitated specialized models, hindering the development of broadly applicable and computationally efficient Protein Language Models (PLMs). In this work, we introduce Prot2Token, a unified framework that overcomes these challenges by converting a wide spectrum of protein-related predictions, from sequence-level properties and residue-specific attributes to complex inter-protein interactions, into a standardized next-token prediction format. At its core, Prot2Token employs an autoregressive decoder, conditioned on embeddings from pre-trained protein encoders and guided by learnable task tokens, to perform diverse predictions. This architecture uniquely facilitates multi-task learning, enabling a single model to master numerous tasks with improved efficiency. We present extensive experimental validation across a variety of benchmarks, demonstrating Prot2Tokens strong predictive power in different types of protein-prediction tasks. Key results include significant speedups (e.g., near 1000x over AlphaFold2 with MSA) and performance often matching or exceeding specialized approaches. Beyond that, we introduce an auxiliary self-supervised decoder pre-training approach to improve spatially sensitive task performance. Prot2Token thus offers a significant step towards a versatile, high-throughput paradigm for protein modeling, promising to accelerate biological discovery and the development of novel therapeutics. The code is available at https://github.com/mahdip72/prot2token .

Pre-trained language models (PLMs) have been the de facto paradigm for most natural language processing (NLP) tasks. This also benefits biomedical domain: researchers from informatics, medicine, and computer science (CS) communities propose various PLMs trained on biomedical datasets, e.g., biomedical text, electronic health records, protein, and DNA sequences for various biomedical tasks. However, the cross-discipline characteristics of biomedical PLMs hinder their spreading among communities; some existing works are isolated from each other without comprehensive comparison and discussions. It expects a survey that not only systematically reviews recent advances of biomedical PLMs and their applications but also standardizes terminology and benchmarks. In this paper, we summarize the recent progress of pre-trained language models in the biomedical domain and their applications in biomedical downstream tasks. Particularly, we discuss the motivations and propose a taxonomy of existing biomedical PLMs. Their applications in biomedical downstream tasks are exhaustively discussed. At last, we illustrate various limitations and future trends, which we hope can provide inspiration for the future research of the research community.

Embedding models have been crucial in enabling various downstream tasks such as semantic similarity, information retrieval, and clustering. Recently, there has been a surge of interest in developing universal text embedding models that can generalize across tasks (e.g., MTEB). However, progress in learning universal multimodal embedding models has been relatively slow despite their importance. In this work, we aim to explore the potential for building universal embeddings capable of handling a wide range of downstream tasks. Our contributions are twofold: (1) MMEB (Massive Multimodal Embedding Benchmark), which covers 4 meta-tasks (i.e. classification, visual question answering, multimodal retrieval, and visual grounding) and 36 datasets, including 20 training and 16 evaluation datasets, and (2) VLM2Vec (Vision-Language Model -> Vector), a contrastive training framework that converts any state-of-the-art vision-language model into an embedding model via training on MMEB. Unlike previous models such as CLIP and BLIP, VLM2Vec can process any combination of images and text to generate a fixed-dimensional vector based on task instructions. We build a series of VLM2Vec models on Phi-3.5-V and evaluate them on MMEB's evaluation split. Our results show that \model achieves an absolute average improvement of 10% to 20% over existing multimodal embedding models on both in-distribution and out-of-distribution datasets in MMEB.

Transformer-based text embedding models have improved their performance on benchmarks like MIRACL and BEIR by increasing their parameter counts. However, this scaling approach introduces significant deployment challenges, including increased inference latency and memory usage. These challenges are particularly severe in retrieval-augmented generation (RAG) applications, where large models' increased memory requirements constrain dataset ingestion capacity, and their higher latency directly impacts query-time performance. While causal language models have addressed similar efficiency challenges using Mixture of Experts (MoE) architectures, this approach hasn't been successfully adapted to the general text embedding setting. In this paper, we introduce Nomic Embed v2, the first general purpose MoE text embedding model. Our model outperforms models in the same parameter class on both monolingual and multilingual benchmarks while also maintaining competitive performance with models twice its size. We open-source all code, models, and evaluation data to ensure full reproducibility of our training pipeline.

Large decoder-only language models (LLMs) are the state-of-the-art models on most of today's NLP tasks and benchmarks. Yet, the community is only slowly adopting these models for text embedding tasks, which require rich contextualized representations. In this work, we introduce LLM2Vec, a simple unsupervised approach that can transform any decoder-only LLM into a strong text encoder. LLM2Vec consists of three simple steps: 1) enabling bidirectional attention, 2) masked next token prediction, and 3) unsupervised contrastive learning. We demonstrate the effectiveness of LLM2Vec by applying it to 3 popular LLMs ranging from 1.3B to 7B parameters and evaluate the transformed models on English word- and sequence-level tasks. We outperform encoder-only models by a large margin on word-level tasks and reach a new unsupervised state-of-the-art performance on the Massive Text Embeddings Benchmark (MTEB). Moreover, when combining LLM2Vec with supervised contrastive learning, we achieve state-of-the-art performance on MTEB among models that train only on publicly available data. Our strong empirical results and extensive analysis demonstrate that LLMs can be effectively transformed into universal text encoders in a parameter-efficient manner without the need for expensive adaptation or synthetic GPT-4 generated data.

While deep learning has revolutionized the prediction of rigid protein structures, modelling the conformational ensembles of Intrinsically Disordered Proteins (IDPs) remains a key frontier. Current AI paradigms present a trade-off: Protein Language Models (PLMs) capture evolutionary statistics but lack explicit physical grounding, while generative models trained to model full ensembles are computationally expensive. In this work we critically assess these limits and propose a path forward. We introduce GeoGraph, a simulation-informed surrogate trained to predict ensemble-averaged statistics of residue-residue contact-map topology directly from sequence. By featurizing coarse-grained molecular dynamics simulations into residue- and sequence-level graph descriptors, we create a robust and information-rich learning target. Our evaluation demonstrates that this approach yields representations that are more predictive of key biophysical properties than existing methods.

Despite being self-supervised, protein language models have shown remarkable performance in fundamental biological tasks such as predicting impact of genetic variation on protein structure and function. The effectiveness of these models on diverse set of tasks suggests that they learn meaningful representations of fitness landscape that can be useful for downstream clinical applications. Here, we interrogate the use of these language models in characterizing known pathogenic mutations in curated, medically actionable genes through an exhaustive search of putative compensatory mutations on each variant's genetic background. Systematic analysis of the predicted effects of these compensatory mutations reveal unappreciated structural features of proteins that are missed by other structure predictors like AlphaFold. While deep mutational scan experiments provide an unbiased estimate of the mutational landscape, we encourage the community to generate and curate rescue mutation experiments to inform the design of more sophisticated co-masking strategies and leverage large language models more effectively for downstream clinical prediction tasks.

Cross-lingual transfer learning is an important property of multilingual large language models (LLMs). But how do LLMs represent relationships between languages? Every language model has an input layer that maps tokens to vectors. This ubiquitous layer of language models is often overlooked. We find that similarities between these input embeddings are highly interpretable and that the geometry of these embeddings differs between model families. In one case (XLM-RoBERTa), embeddings encode language: tokens in different writing systems can be linearly separated with an average of 99.2% accuracy. Another family (mT5) represents cross-lingual semantic similarity: the 50 nearest neighbors for any token represent an average of 7.61 writing systems, and are frequently translations. This result is surprising given that there is no explicit parallel cross-lingual training corpora and no explicit incentive for translations in pre-training objectives. Our research opens the door for investigations in 1) The effect of pre-training and model architectures on representations of languages and 2) The applications of cross-lingual representations embedded in language models.

Large language models (LLMs) have recently demonstrated excellent performance in text embedding tasks. Previous work usually use LoRA to fine-tune existing LLMs, which are limited by the data and training gap between LLMs and embedding models. In this work, we introduce Conan-embedding-v2, a new 1.4B-parameter LLM trained from scratch and fine-tuned as a text embedder. First, we add news data and multilingual pairs for LLM pretraining to bridge the data gap. Based on this, we propose a cross-lingual retrieval dataset that enables the LLM to better integrate embeddings across different languages. Second, whereas LLMs use a causal mask with token-level loss, embedding models use a bidirectional mask with sentence-level loss. This training gap makes full fine-tuning less effective than LoRA. We introduce a soft-masking mechanism to gradually transition between these two types of masks, enabling the model to learn more comprehensive representations. Based on this, we propose a dynamic hard negative mining method that exposes the model to more difficult negative examples throughout the training process. Being intuitive and effective, with only approximately 1.4B parameters, Conan-embedding-v2 achieves SOTA performance on both the Massive Text Embedding Benchmark (MTEB) and Chinese MTEB (May 19, 2025).

Electronic health records (EHR) contain narrative notes that provide extensive details on the medical condition and management of patients. Natural language processing (NLP) of clinical notes can use observed frequencies of clinical terms as predictive features for downstream applications such as clinical decision making and patient trajectory prediction. However, due to the vast number of highly similar and related clinical concepts, a more effective modeling strategy is to represent clinical terms as semantic embeddings via representation learning and use the low dimensional embeddings as feature vectors for predictive modeling. To achieve efficient representation, fine-tuning pretrained language models with biomedical knowledge graphs may generate better embeddings for biomedical terms than those from standard language models alone. These embeddings can effectively discriminate synonymous pairs of from those that are unrelated. However, they often fail to capture different degrees of similarity or relatedness for concepts that are hierarchical in nature. To overcome this limitation, we propose HiPrBERT, a novel biomedical term representation model trained on additionally complied data that contains hierarchical structures for various biomedical terms. We modify an existing contrastive loss function to extract information from these hierarchies. Our numerical experiments demonstrate that HiPrBERT effectively learns the pair-wise distance from hierarchical information, resulting in a substantially more informative embeddings for further biomedical applications

Advancements in DNA sequencing technologies have significantly improved our ability to decode genomic sequences. However, the prediction and interpretation of these sequences remain challenging due to the intricate nature of genetic material. Large language models (LLMs) have introduced new opportunities for biological sequence analysis. Recent developments in genomic language models have underscored the potential of LLMs in deciphering DNA sequences. Nonetheless, existing models often face limitations in robustness and application scope, primarily due to constraints in model structure and training data scale. To address these limitations, we present GENERator, a generative genomic foundation model featuring a context length of 98k base pairs (bp) and 1.2B parameters. Trained on an expansive dataset comprising 386B bp of eukaryotic DNA, the GENERator demonstrates state-of-the-art performance across both established and newly proposed benchmarks. The model adheres to the central dogma of molecular biology, accurately generating protein-coding sequences that translate into proteins structurally analogous to known families. It also shows significant promise in sequence optimization, particularly through the prompt-responsive generation of promoter sequences with specific activity profiles. These capabilities position the GENERator as a pivotal tool for genomic research and biotechnological advancement, enhancing our ability to interpret and predict complex biological systems and enabling precise genomic interventions.

While large language models (LLMs) excel on generation tasks, their decoder-only architecture often limits their potential as embedding models if no further representation finetuning is applied. Does this contradict their claim of generalists? To answer the question, we take a closer look at Mixture-of-Experts (MoE) LLMs. Our study shows that the expert routers in MoE LLMs can serve as an off-the-shelf embedding model with promising performance on a diverse class of embedding-focused tasks, without requiring any finetuning. Moreover, our extensive analysis shows that the MoE routing weights (RW) is complementary to the hidden state (HS) of LLMs, a widely-used embedding. Compared to HS, we find that RW is more robust to the choice of prompts and focuses on high-level semantics. Motivated by the analysis, we propose MoEE combining RW and HS, which achieves better performance than using either separately. Our exploration of their combination and prompting strategy shed several novel insights, e.g., a weighted sum of RW and HS similarities outperforms the similarity on their concatenation. Our experiments are conducted on 6 embedding tasks with 20 datasets from the Massive Text Embedding Benchmark (MTEB). The results demonstrate the significant improvement brought by MoEE to LLM-based embedding without further finetuning.

Large language models (LLMs) have increasingly been explored as powerful text embedders. Existing LLM-based text embedding approaches often leverage the embedding of the final token, typically a reserved special token such as [EOS]. However, these tokens have not been intentionally trained to capture the semantics of the whole context, limiting their capacity as text embeddings, especially for retrieval and re-ranking tasks. We propose to add a new training stage before contrastive learning to enrich the semantics of the final token embedding. This stage employs bidirectional generative reconstruction tasks, namely EBQ2D (Embedding-Based Query-to-Document) and EBD2Q (Embedding-Based Document-to-Query), which interleave to anchor the [EOS] embedding and reconstruct either side of Query-Document pairs. Experimental results demonstrate that our additional training stage significantly improves LLM performance on the Massive Text Embedding Benchmark (MTEB), achieving new state-of-the-art results across different LLM base models and scales.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

In recent years, Large Language Models (LLMs) have achieved significant success in natural language processing (NLP) and various interdisciplinary areas. However, applying LLMs to chemistry is a complex task that requires specialized domain knowledge. This paper provides a thorough exploration of the nuanced methodologies employed in integrating LLMs into the field of chemistry, delving into the complexities and innovations at this interdisciplinary juncture. Specifically, our analysis begins with examining how molecular information is fed into LLMs through various representation and tokenization methods. We then categorize chemical LLMs into three distinct groups based on the domain and modality of their input data, and discuss approaches for integrating these inputs for LLMs. Furthermore, this paper delves into the pretraining objectives with adaptations to chemical LLMs. After that, we explore the diverse applications of LLMs in chemistry, including novel paradigms for their application in chemistry tasks. Finally, we identify promising research directions, including further integration with chemical knowledge, advancements in continual learning, and improvements in model interpretability, paving the way for groundbreaking developments in the field.

The significant advancements of Large Language Models (LLMs) in generative tasks have led to a growing body of work exploring LLM-based embedding models. While these models, employing different pooling and attention strategies, have achieved state-of-the-art performance on public embedding benchmarks, questions still arise about what constitutes an effective design for LLM-based embedding models. However, these models are often trained on different datasets, using different LLM base models or training settings. Moreover, evaluations on public embedding benchmarks often fail to report statistical significance, making it difficult to determine which designs truly contribute to final performance. This complicates the process for practitioners seeking optimal training recipes for LLM-based embedding models. In this study, we conduct a large-scale experiment by training a series of LLM-based embedding models using the same training data and base model but differing in their pooling and attention strategies. The results show that there is no one-size-fits-all solution: while bidirectional attention and an additional trainable pooling layer outperform in text similarity and information retrieval tasks, they do not significantly surpass simpler designs like EOS-last token pooling and default causal attention in clustering and classification tasks. Furthermore, we propose a new pooling strategy, Multi-Layers Trainable Pooling, which transforms the outputs of all hidden layers, rather than just the last layer, using a cross-attention network. This method proves to be statistically superior in text similarity and retrieval tasks compared to existing pooling methods. Overall, this paper sheds light on effective training strategies for LLM-based embedding models.

Word embeddings have been shown to be useful across state-of-the-art systems in many natural language processing tasks, ranging from question answering systems to dependency parsing. (Herbelot and Vecchi, 2015) explored word embeddings and their utility for modeling language semantics. In particular, they presented an approach to automatically map a standard distributional semantic space onto a set-theoretic model using partial least squares regression. We show in this paper that a simple baseline achieves a +51% relative improvement compared to their model on one of the two datasets they used, and yields competitive results on the second dataset.

PaliGemma 2 is an upgrade of the PaliGemma open Vision-Language Model (VLM) based on the Gemma 2 family of language models. We combine the SigLIP-So400m vision encoder that was also used by PaliGemma with the whole range of Gemma 2 models, from the 2B one all the way up to the 27B model. We train these models at three resolutions (224px, 448px, and 896px) in multiple stages to equip them with broad knowledge for transfer via fine-tuning. The resulting family of base models covering different model sizes and resolutions allows us to investigate factors impacting transfer performance (such as learning rate) and to analyze the interplay between the type of task, model size, and resolution. We further increase the number and breadth of transfer tasks beyond the scope of PaliGemma including different OCR-related tasks such as table structure recognition, molecular structure recognition, music score recognition, as well as long fine-grained captioning and radiography report generation, on which PaliGemma 2 obtains state-of-the-art results.

Recently, multimodal large language models (MLLMs) have achieved significant advancements across various domains, and corresponding evaluation benchmarks have been continuously refined and improved. In this process, benchmarks in the scientific domain have played an important role in assessing the reasoning capabilities of MLLMs. However, existing benchmarks still face three key challenges: 1) Insufficient evaluation of models' reasoning abilities in multilingual scenarios; 2) Inadequate assessment of MLLMs' comprehensive modality coverage; 3) Lack of fine-grained annotation of scientific knowledge points. To address these gaps, we propose MME-SCI, a comprehensive and challenging benchmark. We carefully collected 1,019 high-quality question-answer pairs, which involve 3 distinct evaluation modes. These pairs cover four subjects, namely mathematics, physics, chemistry, and biology, and support five languages: Chinese, English, French, Spanish, and Japanese. We conducted extensive experiments on 16 open-source models and 4 closed-source models, and the results demonstrate that MME-SCI is widely challenging for existing MLLMs. For instance, under the Image-only evaluation mode, o4-mini achieved accuracy of only 52.11%, 24.73%, 36.57%, and 29.80% in mathematics, physics, chemistry, and biology, respectively, indicating a significantly higher difficulty level compared to existing benchmarks. More importantly, using MME-SCI's multilingual and fine-grained knowledge attributes, we analyzed existing models' performance in depth and identified their weaknesses in specific domains. The Data and Evaluation Code are available at https://github.com/JCruan519/MME-SCI.

In the past year, MultiModal Large Language Models (MM-LLMs) have undergone substantial advancements, augmenting off-the-shelf LLMs to support MM inputs or outputs via cost-effective training strategies. The resulting models not only preserve the inherent reasoning and decision-making capabilities of LLMs but also empower a diverse range of MM tasks. In this paper, we provide a comprehensive survey aimed at facilitating further research of MM-LLMs. Specifically, we first outline general design formulations for model architecture and training pipeline. Subsequently, we provide brief introductions of 26 existing MM-LLMs, each characterized by its specific formulations. Additionally, we review the performance of MM-LLMs on mainstream benchmarks and summarize key training recipes to enhance the potency of MM-LLMs. Lastly, we explore promising directions for MM-LLMs while concurrently maintaining a real-time tracking website for the latest developments in the field. We hope that this survey contributes to the ongoing advancement of the MM-LLMs domain.

Contextualized embeddings based on large language models (LLMs) are available for various languages, but their coverage is often limited for lower resourced languages. Training LLMs for such languages is often difficult due to insufficient data and high computational cost. Especially for very low resource languages, static word embeddings thus still offer a viable alternative. There is, however, a notable lack of comprehensive repositories with such embeddings for diverse languages. To address this, we present LowREm, a centralized repository of static embeddings for 87 low-resource languages. We also propose a novel method to enhance GloVe-based embeddings by integrating multilingual graph knowledge, utilizing another source of knowledge. We demonstrate the superior performance of our enhanced embeddings as compared to contextualized embeddings extracted from XLM-R on sentiment analysis. Our code and data are publicly available under https://huggingface.co/DFKI.

Recent advancements in large language models (LLMs) based embedding models have established new state-of-the-art benchmarks for text embedding tasks, particularly in dense vector-based retrieval. However, these models predominantly focus on English, leaving multilingual embedding capabilities largely unexplored. To address this limitation, we present LUSIFER, a novel zero-shot approach that adapts LLM-based embedding models for multilingual tasks without requiring multilingual supervision. LUSIFER's architecture combines a multilingual encoder, serving as a language-universal learner, with an LLM-based embedding model optimized for embedding-specific tasks. These components are seamlessly integrated through a minimal set of trainable parameters that act as a connector, effectively transferring the multilingual encoder's language understanding capabilities to the specialized embedding model. Additionally, to comprehensively evaluate multilingual embedding performance, we introduce a new benchmark encompassing 5 primary embedding tasks, 123 diverse datasets, and coverage across 14 languages. Extensive experimental results demonstrate that LUSIFER significantly enhances the multilingual performance across various embedding tasks, particularly for medium and low-resource languages, without requiring explicit multilingual training data.

Token embeddings, a mapping from discrete lexical symbols to continuous vectors, are at the heart of any language model (LM). However, lexical symbol meanings can also be determined and even redefined by their structural role in a long context. In this paper, we ask: is it possible for a language model to be performant without any fixed token embeddings? Such a language model would have to rely entirely on the co-occurence and repetition of tokens in the context rather than the a priori identity of any token. To answer this, we study lexinvariantlanguage models that are invariant to lexical symbols and therefore do not need fixed token embeddings in practice. First, we prove that we can construct a lexinvariant LM to converge to the true language model at a uniform rate that is polynomial in terms of the context length, with a constant factor that is sublinear in the vocabulary size. Second, to build a lexinvariant LM, we simply encode tokens using random Gaussian vectors, such that each token maps to the same representation within each sequence but different representations across sequences. Empirically, we demonstrate that it can indeed attain perplexity comparable to that of a standard language model, given a sufficiently long context. We further explore two properties of the lexinvariant language models: First, given text generated from a substitution cipher of English, it implicitly implements Bayesian in-context deciphering and infers the mapping to the underlying real tokens with high accuracy. Second, it has on average 4X better accuracy over synthetic in-context reasoning tasks. Finally, we discuss regularizing standard language models towards lexinvariance and potential practical applications.

Large language models (LLMs) trained on general domain corpora showed remarkable results on natural language processing (NLP) tasks. However, previous research demonstrated LLMs trained using domain-focused corpora perform better on specialized tasks. Inspired by this pivotal insight, we developed INDUS, a comprehensive suite of LLMs tailored for the Earth science, biology, physics, heliophysics, planetary sciences and astrophysics domains and trained using curated scientific corpora drawn from diverse data sources. The suite of models include: (1) an encoder model trained using domain-specific vocabulary and corpora to address natural language understanding tasks, (2) a contrastive-learning-based general text embedding model trained using a diverse set of datasets drawn from multiple sources to address information retrieval tasks and (3) smaller versions of these models created using knowledge distillation techniques to address applications which have latency or resource constraints. We also created three new scientific benchmark datasets namely, CLIMATE-CHANGE-NER (entity-recognition), NASA-QA (extractive QA) and NASA-IR (IR) to accelerate research in these multi-disciplinary fields. Finally, we show that our models outperform both general-purpose encoders (RoBERTa) and existing domain-specific encoders (SciBERT) on these new tasks as well as existing benchmark tasks in the domains of interest.

Large Language Models (LLMs) increasingly incorporate multilingual capabilities, fueling the demand to transfer them into target language-specific models. However, most approaches, which blend the source model's embedding by replacing the source vocabulary with the target language-specific vocabulary, may constrain expressive capacity in the target language since the source model is predominantly trained on English data. In this paper, we propose Semantic Aware Linear Transfer (SALT), a novel cross-lingual transfer technique that recycles embeddings from target language Pre-trained Language Models (PLMs) to transmit the deep representational strengths of PLM-derived embedding to LLMs. SALT derives unique regression lines based on the similarity in the overlap of the source and target vocabularies, to handle each non-overlapping token's embedding space. Our extensive experiments show that SALT significantly outperforms other transfer methods and achieves lower loss with accelerating faster convergence during language adaptation. Notably, SALT obtains remarkable performance in cross-lingual understanding setups compared to other methods. Furthermore, we highlight the scalable use of PLMs to enhance the functionality of contemporary LLMs by conducting experiments with varying architectures.

Large Language Models (LLMs) excel in various natural language processing tasks, but leveraging them for dense passage embedding remains challenging. This is due to their causal attention mechanism and the misalignment between their pre-training objectives and the text ranking tasks. Despite some recent efforts to address these issues, existing frameworks for LLM-based text embeddings have been limited by their support for only a limited range of LLM architectures and fine-tuning strategies, limiting their practical application and versatility. In this work, we introduce the Unified framework for Large Language Model Embedding (ULLME), a flexible, plug-and-play implementation that enables bidirectional attention across various LLMs and supports a range of fine-tuning strategies. We also propose Generation-augmented Representation Learning (GRL), a novel fine-tuning method to boost LLMs for text embedding tasks. GRL enforces consistency between representation-based and generation-based relevance scores, leveraging LLMs' powerful generative abilities for learning passage embeddings. To showcase our framework's flexibility and effectiveness, we release three pre-trained models from ULLME with different backbone architectures, ranging from 1.5B to 8B parameters, all of which demonstrate strong performance on the Massive Text Embedding Benchmark. Our framework is publicly available at: https://github.com/nlp-uoregon/ullme. A demo video for ULLME can also be found at https://rb.gy/ws1ile.

Nanobodies, single-domain antibody fragments derived from camelid heavy-chain-only antibodies, exhibit unique advantages such as compact size, high stability, and strong binding affinity, making them valuable tools in therapeutics and diagnostics. While recent advances in pretrained protein and antibody language models (PPLMs and PALMs) have greatly enhanced biomolecular understanding, nanobody-specific modeling remains underexplored and lacks a unified benchmark. To address this gap, we introduce NbBench, the first comprehensive benchmark suite for nanobody representation learning. Spanning eight biologically meaningful tasks across nine curated datasets, NbBench encompasses structure annotation, binding prediction, and developability assessment. We systematically evaluate eleven representative models--including general-purpose protein LMs, antibody-specific LMs, and nanobody-specific LMs--in a frozen setting. Our analysis reveals that antibody language models excel in antigen-related tasks, while performance on regression tasks such as thermostability and affinity remains challenging across all models. Notably, no single model consistently outperforms others across all tasks. By standardizing datasets, task definitions, and evaluation protocols, NbBench offers a reproducible foundation for assessing and advancing nanobody modeling.

Neural language models are probabilistic models of human text. They are predominantly trained using maximum likelihood estimation (MLE), which is equivalent to minimizing the forward cross-entropy between the empirical data distribution and the model distribution. However, various degeneration phenomena are still widely observed when decoding from the distributions learned by such models. We establish that the forward cross-entropy is suboptimal as a distance metric for aligning human and model distribution due to its (1) recall-prioritization (2) negative diversity ignorance and (3) train-test mismatch. In this paper, we propose Earth Mover Distance Optimization (EMO) for auto-regressive language modeling. EMO capitalizes on the inherent properties of earth mover distance to address the aforementioned challenges. Due to the high complexity of direct computation, we further introduce a feasible upper bound for EMO to ease end-to-end training. Upon extensive evaluation of language models trained using EMO and MLE. We find that EMO demonstrates a consistently better language modeling performance than MLE across domains. Moreover, EMO demonstrates noteworthy enhancements in downstream performance with minimal fine-tuning on merely 25,000 sentences. This highlights the tremendous potential of EMO as a lightweight calibration method for enhancing large-scale pre-trained language models.

Generative protein language models are a natural way to design new proteins with desired functions. However, current models are either difficult to direct to produce a protein from a specific family of interest, or must be trained on a large multiple sequence alignment (MSA) from the specific family of interest, making them unable to benefit from transfer learning across families. To address this, we propose Protein Evolutionary Transformer (PoET), an autoregressive generative model of whole protein families that learns to generate sets of related proteins as sequences-of-sequences across tens of millions of natural protein sequence clusters. PoET can be used as a retrieval-augmented language model to generate and score arbitrary modifications conditioned on any protein family of interest, and can extrapolate from short context lengths to generalize well even for small families. This is enabled by a unique Transformer layer; we model tokens sequentially within sequences while attending between sequences order invariantly, allowing PoET to scale to context lengths beyond those used during training. In extensive experiments on deep mutational scanning datasets, we show that PoET outperforms existing protein language models and evolutionary sequence models for variant function prediction across proteins of all MSA depths. We also demonstrate PoET's ability to controllably generate new protein sequences.

The rapid progress of Multimodal Large Language Models(MLLMs) has transformed the AI landscape. These models combine pre-trained LLMs with various modality encoders. This integration requires a systematic understanding of how different modalities connect to the language backbone. Our survey presents an LLM-centric analysis of current approaches. We examine methods for transforming and aligning diverse modal inputs into the language embedding space. This addresses a significant gap in existing literature. We propose a classification framework for MLLMs based on three key dimensions. First, we examine architectural strategies for modality integration. This includes both the specific integration mechanisms and the fusion level. Second, we categorize representation learning techniques as either joint or coordinate representations. Third, we analyze training paradigms, including training strategies and objective functions. By examining 125 MLLMs developed between 2021 and 2025, we identify emerging patterns in the field. Our taxonomy provides researchers with a structured overview of current integration techniques. These insights aim to guide the development of more robust multimodal integration strategies for future models built on pre-trained foundations.

The ability of generative large language models (LLMs) to perform in-context learning has given rise to a large body of research into how best to prompt models for various natural language processing tasks. In this paper, we focus on machine translation (MT), a task that has been shown to benefit from in-context translation examples. However no systematic studies have been published on how best to select examples, and mixed results have been reported on the usefulness of similarity-based selection over random selection. We provide a study covering multiple LLMs and multiple in-context example retrieval strategies, comparing multilingual sentence embeddings. We cover several language directions, representing different levels of language resourcedness (English into French, German, Swahili and Wolof). Contrarily to previously published results, we find that sentence embedding similarity can improve MT, especially for low-resource language directions, and discuss the balance between selection pool diversity and quality. We also highlight potential problems with the evaluation of LLM-based MT and suggest a more appropriate evaluation protocol, adapting the COMET metric to the evaluation of LLMs. Code and outputs are freely available at https://github.com/ArmelRandy/ICL-MT.

Most pre-trained language models (PLMs) construct word representations at subword level with Byte-Pair Encoding (BPE) or its variations, by which OOV (out-of-vocab) words are almost avoidable. However, those methods split a word into subword units and make the representation incomplete and fragile. In this paper, we propose a character-aware pre-trained language model named CharBERT improving on the previous methods (such as BERT, RoBERTa) to tackle these problems. We first construct the contextual word embedding for each token from the sequential character representations, then fuse the representations of characters and the subword representations by a novel heterogeneous interaction module. We also propose a new pre-training task named NLM (Noisy LM) for unsupervised character representation learning. We evaluate our method on question answering, sequence labeling, and text classification tasks, both on the original datasets and adversarial misspelling test sets. The experimental results show that our method can significantly improve the performance and robustness of PLMs simultaneously. Pretrained models, evaluation sets, and code are available at https://github.com/wtma/CharBERT

We introduce StableLM 2 1.6B, the first in a new generation of our language model series. In this technical report, we present in detail the data and training procedure leading to the base and instruction-tuned versions of StableLM 2 1.6B. The weights for both models are available via Hugging Face for anyone to download and use. The report contains thorough evaluations of these models, including zero- and few-shot benchmarks, multilingual benchmarks, and the MT benchmark focusing on multi-turn dialogues. At the time of publishing this report, StableLM 2 1.6B was the state-of-the-art open model under 2B parameters by a significant margin. Given its appealing small size, we also provide throughput measurements on a number of edge devices. In addition, we open source several quantized checkpoints and provide their performance metrics compared to the original model.

Predicting peptide--major histocompatibility complex I (pMHC-I) binding affinity remains challenging due to extreme allelic diversity (sim30,000 HLA alleles), severe data scarcity for most alleles, and noisy experimental measurements. Current methods particularly struggle with underrepresented alleles and quantitative binding prediction. We test whether domain-specific continued pre-training of protein language models is beneficial for their application to pMHC-I binding affinity prediction. Starting from ESM Cambrian (300M parameters), we perform masked-language modeling (MLM)-based continued pre-training on HLA-associated peptides (epitopes), testing two input formats: epitope sequences alone versus epitopes concatenated with HLA heavy chain sequences. We then fine-tune for functional IC_{50} binding affinity prediction using only high-quality quantitative data, avoiding mass spectrometry biases that are inherited by existing methods.

Vietnam ranks among the top countries in terms of both internet traffic and online toxicity. As a result, implementing embedding models for recommendation and content control duties in applications is crucial. However, a lack of large-scale test datasets, both in volume and task diversity, makes it tricky for scientists to effectively evaluate AI models before deploying them in real-world, large-scale projects. To solve this important problem, we introduce a Vietnamese benchmark, VN-MTEB for embedding models, which we created by translating a large number of English samples from the Massive Text Embedding Benchmark using our new automated framework. We leverage the strengths of large language models (LLMs) and cutting-edge embedding models to conduct translation and filtering processes to retain high-quality samples, guaranteeing a natural flow of language and semantic fidelity while preserving named entity recognition (NER) and code snippets. Our comprehensive benchmark consists of 41 datasets from six tasks specifically designed for Vietnamese text embeddings. In our analysis, we find that bigger and more complex models using Rotary Positional Embedding outperform those using Absolute Positional Embedding in embedding tasks. Datasets are available at HuggingFace: https://huggingface.co/collections/GreenNode/vn-mteb-68871433f0f7573b8e1a6686

This paper provides a comprehensive survey of the latest research on multilingual large language models (MLLMs). MLLMs not only are able to understand and generate language across linguistic boundaries, but also represent an important advancement in artificial intelligence. We first discuss the architecture and pre-training objectives of MLLMs, highlighting the key components and methodologies that contribute to their multilingual capabilities. We then discuss the construction of multilingual pre-training and alignment datasets, underscoring the importance of data quality and diversity in enhancing MLLM performance. An important focus of this survey is on the evaluation of MLLMs. We present a detailed taxonomy and roadmap covering the assessment of MLLMs' cross-lingual knowledge, reasoning, alignment with human values, safety, interpretability and specialized applications. Specifically, we extensively discuss multilingual evaluation benchmarks and datasets, and explore the use of LLMs themselves as multilingual evaluators. To enhance MLLMs from black to white boxes, we also address the interpretability of multilingual capabilities, cross-lingual transfer and language bias within these models. Finally, we provide a comprehensive review of real-world applications of MLLMs across diverse domains, including biology, medicine, computer science, mathematics and law. We showcase how these models have driven innovation and improvements in these specialized fields while also highlighting the challenges and opportunities in deploying MLLMs within diverse language communities and application scenarios. We listed the paper related in this survey and publicly available at https://github.com/tjunlp-lab/Awesome-Multilingual-LLMs-Papers.

With the growing prominence of antibody-based therapeutics, antibody engineering has gained increasing attention as a critical area of research and development. Recent progress in transformer-based protein large language models (LLMs) has demonstrated promising applications in protein sequence design and structural prediction. Moreover, the availability of large-scale antibody datasets such as the Observed Antibody Space (OAS) database has opened new avenues for the development of LLMs specialized for processing antibody sequences. Among these, RoBERTa has demonstrated improved performance relative to BERT, while maintaining a smaller parameter count (125M) compared to the BERT-based protein model, ProtBERT (420M). This reduced model size enables more efficient deployment in antibody-related applications. However, despite the numerous advantages of the RoBERTa architecture, antibody-specific foundational models built upon it have remained inaccessible to the research community. In this study, we introduce Ab-RoBERTa, a RoBERTa-based antibody-specific LLM, which is publicly available at https://huggingface.co/mogam-ai/Ab-RoBERTa. This resource is intended to support a wide range of antibody-related research applications including paratope prediction or humanness assessment.

Large Language Models (LLMs), with their remarkable task-handling capabilities and innovative outputs, have catalyzed significant advancements across a spectrum of fields. However, their proficiency within specialized domains such as biomolecular studies remains limited. To address this challenge, we introduce Mol-Instructions, a meticulously curated, comprehensive instruction dataset expressly designed for the biomolecular realm. Mol-Instructions is composed of three pivotal components: molecule-oriented instructions, protein-oriented instructions, and biomolecular text instructions, each curated to enhance the understanding and prediction capabilities of LLMs concerning biomolecular features and behaviors. Through extensive instruction tuning experiments on the representative LLM, we underscore the potency of Mol-Instructions to enhance the adaptability and cognitive acuity of large models within the complex sphere of biomolecular studies, thereby promoting advancements in the biomolecular research community. Mol-Instructions is made publicly accessible for future research endeavors and will be subjected to continual updates for enhanced applicability.

Hidden Markov Models (HMMs) are foundational tools for modeling sequential data with latent Markovian structure, yet fitting them to real-world data remains computationally challenging. In this work, we show that pre-trained large language models (LLMs) can effectively model data generated by HMMs via in-context learning (ICL)x2013their ability to infer patterns from examples within a prompt. On a diverse set of synthetic HMMs, LLMs achieve predictive accuracy approaching the theoretical optimum. We uncover novel scaling trends influenced by HMM properties, and offer theoretical conjectures for these empirical observations. We also provide practical guidelines for scientists on using ICL as a diagnostic tool for complex data. On real-world animal decision-making tasks, ICL achieves competitive performance with models designed by human experts. To our knowledge, this is the first demonstration that ICL can learn and predict HMM-generated sequencesx2013an advance that deepens our understanding of in-context learning in LLMs and establishes its potential as a powerful tool for uncovering hidden structure in complex scientific data.

Here we show that a Large Language Model (LLM) can serve as a foundation model for a Chemical Language Model (CLM) which performs at or above the level of CLMs trained solely on chemical SMILES string data. Using supervised fine-tuning (SFT) and direct preference optimization (DPO) on the open-source Llama LLM, we demonstrate that we can train an LLM to respond to prompts such as generating molecules with properties of interest to drug development. This overall framework allows an LLM to not just be a chatbot client for chemistry and materials tasks, but can be adapted to speak more directly as a CLM which can generate molecules with user-specified properties.

Large language models (LLMs) have achieved remarkable success and demonstrated superior performance across various tasks, including natural language processing (NLP), weather forecasting, biological protein folding, text generation, and solving mathematical problems. However, many real-world data exhibit highly non-Euclidean latent hierarchical anatomy, such as protein networks, transportation networks, financial networks, brain networks, and linguistic structures or syntactic trees in natural languages. Effectively learning intrinsic semantic entailment and hierarchical relationships from these raw, unstructured input data using LLMs remains an underexplored area. Due to its effectiveness in modeling tree-like hierarchical structures, hyperbolic geometry -- a non-Euclidean space -- has rapidly gained popularity as an expressive latent representation space for complex data modeling across domains such as graphs, images, languages, and multi-modal data. Here, we provide a comprehensive and contextual exposition of recent advancements in LLMs that leverage hyperbolic geometry as a representation space to enhance semantic representation learning and multi-scale reasoning. Specifically, the paper presents a taxonomy of the principal techniques of Hyperbolic LLMs (HypLLMs) in terms of four main categories: (1) hyperbolic LLMs through exp/log maps; (2) hyperbolic fine-tuned models; (3) fully hyperbolic LLMs, and (4) hyperbolic state-space models. We also explore crucial potential applications and outline future research directions. A repository of key papers, models, datasets, and code implementations is available at https://github.com/sarangp2402/Hyperbolic-LLM-Models/tree/main.

Sentence embeddings are crucial in measuring semantic similarity. Most recent studies employed large language models (LLMs) to learn sentence embeddings. Existing LLMs mainly adopted autoregressive architecture without explicit backward dependency modeling. Therefore, we examined the effects of backward dependencies in LLMs for semantic similarity measurements. Concretely, we propose a novel model: backward dependency enhanced large language model (BeLLM). It learns sentence embeddings via transforming specific attention layers from uni- to bi-directional. We extensively experiment across various semantic textual similarity (STS) tasks and downstream applications. BeLLM achieves state-of-the-art performance in varying scenarios. It shows that auto-regressive LLMs benefit from backward dependencies for sentence embeddings.

The rapid advance of Large Language Models (LLMs) has catalyzed the development of Vision-Language Models (VLMs). Monolithic VLMs, which avoid modality-specific encoders, offer a promising alternative to the compositional ones but face the challenge of inferior performance. Most existing monolithic VLMs require tuning pre-trained LLMs to acquire vision abilities, which may degrade their language capabilities. To address this dilemma, this paper presents a novel high-performance monolithic VLM named HoVLE. We note that LLMs have been shown capable of interpreting images, when image embeddings are aligned with text embeddings. The challenge for current monolithic VLMs actually lies in the lack of a holistic embedding module for both vision and language inputs. Therefore, HoVLE introduces a holistic embedding module that converts visual and textual inputs into a shared space, allowing LLMs to process images in the same way as texts. Furthermore, a multi-stage training strategy is carefully designed to empower the holistic embedding module. It is first trained to distill visual features from a pre-trained vision encoder and text embeddings from the LLM, enabling large-scale training with unpaired random images and text tokens. The whole model further undergoes next-token prediction on multi-modal data to align the embeddings. Finally, an instruction-tuning stage is incorporated. Our experiments show that HoVLE achieves performance close to leading compositional models on various benchmarks, outperforming previous monolithic models by a large margin. Model available at https://huggingface.co/OpenGVLab/HoVLE.

Large language models (LLMs) are introducing a paradigm shift in molecular discovery by enabling text-guided interaction with chemical spaces through natural language, symbolic notations, with emerging extensions to incorporate multi-modal inputs. To advance the new field of LLM for molecular discovery, this survey provides an up-to-date and forward-looking review of the emerging use of LLMs for two central tasks: molecule generation and molecule optimization. Based on our proposed taxonomy for both problems, we analyze representative techniques in each category, highlighting how LLM capabilities are leveraged across different learning settings. In addition, we include the commonly used datasets and evaluation protocols. We conclude by discussing key challenges and future directions, positioning this survey as a resource for researchers working at the intersection of LLMs and molecular science. A continuously updated reading list is available at https://github.com/REAL-Lab-NU/Awesome-LLM-Centric-Molecular-Discovery.

The world of language models is going through turbulent times, better and ever larger models are coming out at an unprecedented speed. However, we argue that, especially for the scientific community, encoder models of up to 1 billion parameters are still very much needed, their primary usage being in enriching large collections of data with metadata necessary for downstream research. We investigate the best way to ensure the existence of such encoder models on the set of very closely related languages - Croatian, Serbian, Bosnian and Montenegrin, by setting up a diverse benchmark for these languages, and comparing the trained-from-scratch models with the new models constructed via additional pretraining of existing multilingual models. We show that comparable performance to dedicated from-scratch models can be obtained by additionally pretraining available multilingual models even with a limited amount of computation. We also show that neighboring languages, in our case Slovenian, can be included in the additional pretraining with little to no loss in the performance of the final model.

Large Language Model (LLM) pretraining, finetuning, and evaluation rely on input-space reconstruction and generative capabilities. Yet, it has been observed in vision that embedding-space training objectives, e.g., with Joint Embedding Predictive Architectures (JEPAs), are far superior to their input-space counterpart. That mismatch in how training is achieved between language and vision opens up a natural question: {\em can language training methods learn a few tricks from the vision ones?} The lack of JEPA-style LLM is a testimony of the challenge in designing such objectives for language. In this work, we propose a first step in that direction where we develop LLM-JEPA, a JEPA based solution for LLMs applicable both to finetuning and pretraining. Thus far, LLM-JEPA is able to outperform the standard LLM training objectives by a significant margin across models, all while being robust to overfiting. Those findings are observed across numerous datasets (NL-RX, GSM8K, Spider, RottenTomatoes) and various models from the Llama3, OpenELM, Gemma2 and Olmo families. Code: https://github.com/rbalestr-lab/llm-jepa.

Multimodal large language models (MLLMs) have shown promising advancements in general visual and language understanding. However, the representation of multimodal information using MLLMs remains largely unexplored. In this work, we introduce a new framework, E5-V, designed to adapt MLLMs for achieving universal multimodal embeddings. Our findings highlight the significant potential of MLLMs in representing multimodal inputs compared to previous approaches. By leveraging MLLMs with prompts, E5-V effectively bridges the modality gap between different types of inputs, demonstrating strong performance in multimodal embeddings even without fine-tuning. We propose a single modality training approach for E5-V, where the model is trained exclusively on text pairs. This method demonstrates significant improvements over traditional multimodal training on image-text pairs, while reducing training costs by approximately 95%. Additionally, this approach eliminates the need for costly multimodal training data collection. Extensive experiments across four types of tasks demonstrate the effectiveness of E5-V. As a universal multimodal model, E5-V not only achieves but often surpasses state-of-the-art performance in each task, despite being trained on a single modality.

Protein modeling is an increasingly popular area of machine learning research. Semi-supervised learning has emerged as an important paradigm in protein modeling due to the high cost of acquiring supervised protein labels, but the current literature is fragmented when it comes to datasets and standardized evaluation techniques. To facilitate progress in this field, we introduce the Tasks Assessing Protein Embeddings (TAPE), a set of five biologically relevant semi-supervised learning tasks spread across different domains of protein biology. We curate tasks into specific training, validation, and test splits to ensure that each task tests biologically relevant generalization that transfers to real-life scenarios. We benchmark a range of approaches to semi-supervised protein representation learning, which span recent work as well as canonical sequence learning techniques. We find that self-supervised pretraining is helpful for almost all models on all tasks, more than doubling performance in some cases. Despite this increase, in several cases features learned by self-supervised pretraining still lag behind features extracted by state-of-the-art non-neural techniques. This gap in performance suggests a huge opportunity for innovative architecture design and improved modeling paradigms that better capture the signal in biological sequences. TAPE will help the machine learning community focus effort on scientifically relevant problems. Toward this end, all data and code used to run these experiments are available at https://github.com/songlab-cal/tape.

Recent multilingual pretrained language models (mPLMs) often avoid using language embeddings -- learnable vectors assigned to different languages. These embeddings are discarded for two main reasons: (1) mPLMs are expected to have a single, unified parameter set across all languages, and (2) they need to function seamlessly as universal text encoders without requiring language IDs as input. However, this removal increases the burden on token embeddings to encode all language-specific information, which may hinder the model's ability to produce more language-neutral representations. To address this challenge, we propose Language-Script Aware Multilingual Pretraining (LangSAMP), a method that incorporates both language and script embeddings to enhance representation learning while maintaining a simple architecture. Specifically, we integrate these embeddings into the output of the transformer blocks before passing the final representations to the language modeling head for prediction. We apply LangSAMP to the continual pretraining of XLM-R on a highly multilingual corpus covering more than 500 languages. The resulting model consistently outperforms the baseline. Extensive analysis further shows that language/script embeddings encode language/script-specific information, which improves the selection of source languages for crosslingual transfer. We make our code and models publicly available at https://github.com/cisnlp/LangSAMP.

The availability of different pre-trained semantic models enabled the quick development of machine learning components for downstream applications. Despite the availability of abundant text data for low resource languages, only a few semantic models are publicly available. Publicly available pre-trained models are usually built as a multilingual version of semantic models that can not fit well for each language due to context variations. In this work, we introduce different semantic models for Amharic. After we experiment with the existing pre-trained semantic models, we trained and fine-tuned nine new different models using a monolingual text corpus. The models are build using word2Vec embeddings, distributional thesaurus (DT), contextual embeddings, and DT embeddings obtained via network embedding algorithms. Moreover, we employ these models for different NLP tasks and investigate their impact. We find that newly trained models perform better than pre-trained multilingual models. Furthermore, models based on contextual embeddings from RoBERTA perform better than the word2Vec models.

Self-supervised neural language models have recently achieved unprecedented success, from natural language processing to learning the languages of biological sequences and organic molecules. These models have demonstrated superior performance in the generation, structure classification, and functional predictions for proteins and molecules with learned representations. However, most of the masking-based pre-trained language models are not designed for generative design, and their black-box nature makes it difficult to interpret their design logic. Here we propose BLMM Crystal Transformer, a neural network based probabilistic generative model for generative and tinkering design of inorganic materials. Our model is built on the blank filling language model for text generation and has demonstrated unique advantages in learning the "materials grammars" together with high-quality generation, interpretability, and data efficiency. It can generate chemically valid materials compositions with as high as 89.7\% charge neutrality and 84.8\% balanced electronegativity, which are more than 4 and 8 times higher compared to a pseudo random sampling baseline. The probabilistic generation process of BLMM allows it to recommend tinkering operations based on learned materials chemistry and makes it useful for materials doping. Combined with the TCSP crysal structure prediction algorithm, We have applied our model to discover a set of new materials as validated using DFT calculations. Our work thus brings the unsupervised transformer language models based generative artificial intelligence to inorganic materials. A user-friendly web app has been developed for computational materials doping and can be accessed freely at www.materialsatlas.org/blmtinker.

We introduce SemCSE, an unsupervised method for learning semantic embeddings of scientific texts. Building on recent advances in contrastive learning for text embeddings, our approach leverages LLM-generated summaries of scientific abstracts to train a model that positions semantically related summaries closer together in the embedding space. This resulting objective ensures that the model captures the true semantic content of a text, in contrast to traditional citation-based approaches that do not necessarily reflect semantic similarity. To validate this, we propose a novel benchmark designed to assess a model's ability to understand and encode the semantic content of scientific texts, demonstrating that our method enforces a stronger semantic separation within the embedding space. Additionally, we evaluate SemCSE on the comprehensive SciRepEval benchmark for scientific text embeddings, where it achieves state-of-the-art performance among models of its size, thus highlighting the benefits of a semantically focused training approach.

While Language Models have become workhorses for NLP, their interplay with textual knowledge graphs (KGs) - structured memories of general or domain knowledge - is actively researched. Current embedding methodologies for such graphs typically either (i) linearize graphs for embedding them using sequential Language Models (LMs), which underutilize structural information, or (ii) use Graph Neural Networks (GNNs) to preserve graph structure, while GNNs cannot represent textual features as well as a pre-trained LM could. In this work we introduce a novel language model, the Graph Language Model (GLM), that integrates the strengths of both approaches, while mitigating their weaknesses. The GLM parameters are initialized from a pretrained LM, to facilitate nuanced understanding of individual concepts and triplets. Simultaneously, its architectural design incorporates graph biases, thereby promoting effective knowledge distribution within the graph. Empirical evaluations on relation classification tasks on ConceptNet subgraphs reveal that GLM embeddings surpass both LM- and GNN-based baselines in supervised and zero-shot settings.

The extensive memory footprint of pre-trained language models (PLMs) can hinder deployment in memory-constrained settings, such as cloud environments or on-device. PLMs use embedding matrices to represent extensive vocabularies, forming a large proportion of the model parameters. While previous work towards parameter-efficient PLM development has considered pruning parameters within the transformer layers, pruning the embedding matrix as part of fine-tuning or inference has yet to be explored. We first demonstrate that a significant proportion of the vocabulary remains unused in these scenarios. We then propose a simple yet effective approach that leverages this finding to minimize the memory footprint of the embedding matrix. We show that this approach provides substantial reductions in memory usage across a wide range of models and tasks. Notably, our approach maintains equivalent downstream task performance while allowing a more efficient use of compute resources.