The identification of protein homologs in large databases using conventional methods, such as protein sequence comparison, often misses remote homologs. Here, we offer an ultrafast, highly sensitive method, dense homolog retriever (DHR), for detecting homologs on the basis of a protein language model and dense retrieval techniques. Its dual-encoder architecture generates different embeddings for the same protein sequence and easily locates homologs by comparing these representations. Its alignment-free nature improves speed and the protein language model incorporates rich evolutionary and structural information within DHR embeddings. DHR achieves a >10% increase in sensitivity compared to previous methods and a >56% increase in sensitivity at the superfamily level for samples that are challenging to identify using alignment-based approaches. It is up to 22 times faster than traditional methods such as PSI-BLAST and DIAMOND and up to 28,700 times faster than HMMER. The new remote homologs exclusively found by DHR are useful for revealing connections between well-characterized proteins and improving our knowledge of protein evolution, structure and function.

Recently, large language models (LLMs) have evolved into interactive agents, proficient in planning, tool use, and task execution across various tasks. However, without agent-tuning, open-source models like LLaMA2 currently struggle to match the efficiency of larger models such as GPT-4 in scientific applications due to a lack of agent-tuning datasets. In response, we introduce MIMIR, a streamlined platform offering a customizable pipeline that enables users to leverage both private knowledge and publicly available, legally compliant datasets at scale for agent tuning. Additionally, MIMIR supports the generation of general instruction-tuning datasets from the same input. This dual capability ensures LLM agents developed through the platform possess specific agent abilities and general competencies. MIMIR integrates these features into an end-to-end platform, facilitating everything from the uploading of scientific data to one-click agent fine-tuning. MIMIR is publicly released and actively maintained at https://github.com/gersteinlab/MIMIR, along with a demo video1 for a quick start, calling for broader development.

Large language models (LLMs) excel at a variety of natural language processing tasks, yet they struggle to generate personalized content for individuals, particularly in real-world scenarios like scientific writing. Addressing this challenge, we introduce Step-Back Profiling to personalize LLMs by distilling user history into concise profiles, including essential traits and preferences of users. Regarding our experiments, we construct a Personalized Scientific Writing (PSW) dataset to study multiuser personalization. PSW requires the models to write scientific papers given specialized author groups with diverse academic backgrounds. As for the results, we demonstrate the effectiveness of capturing user characteristics via Step-Back Profiling for collaborative writing. Moreover, our approach outperforms the baselines by up to 3.6 points on the general personalization benchmark (LaMP), including 7 personalization LLM tasks. Our extensive ablation studies validate the contributions of different components in our method and provide insights into our task definition.

Inverse protein folding, which aims to design amino acid sequences for desired protein structures, is fundamental to protein engineering and therapeutic development. While recent deep-learning approaches have made remarkable progress in addressing this challenge, they typically represent biochemical properties as discrete features associated with individual residues. Here, we present BC-Design, an approach that explicitly represents these properties as decorations on randomly sampled points on exterior surfaces and within internally bound regions representing the complete molecular extent of the protein. This provides a more natural way to capture the spatial distribution of properties. We demonstrate that BC-Design significantly outperforms all current methods, improving sequence recovery from 67% to 88.37% over the state-of-the-art methods (a 21.32% absolute improvement) and reducing perplexity from 2.4 to 1.47 (a 39.51% relative improvement) on the CATH 4.2 benchmark. Notably, our model exhibits robust generalization across diverse protein characteristics, achieving consistently high performance on proteins of varying sizes (50-500 residues), structural complexity (measured by contact order), and all major CATH fold classes. Through ablation tests, we compare the relative contribution of both structure encoding information and the encoded property information, and we show that both substantially contribute equally to this strong performance. Overall, this opens new avenues for computational protein engineering and drug discovery.

Despite Large Language Models (LLMs) like GPT-4 achieving impressive results in function-level code generation, they struggle with repository-scale code understanding (e.g., coming up with the right arguments for calling routines), requiring a deeper comprehension of complex file interactions. Also, recently, people have developed LLM agents that attempt to interact with repository code (e.g., compiling and evaluating its execution), prompting the need to evaluate their performance. These gaps have motivated our development of ML-Bench, a benchmark rooted in real-world programming applications that leverage existing code repositories to perform tasks. Addressing the need for LLMs to interpret long code contexts and translate instructions into precise, executable scripts, ML-Bench encompasses annotated 9,641 examples across 18 GitHub repositories, challenging LLMs to accommodate user-specified arguments and documentation intricacies effectively. To evaluate both LLMs and AI agents, two setups are employed: ML-LLM-Bench for assessing LLMs' text-to-code conversion within a predefined deployment environment, and ML-Agent-Bench for testing autonomous agents in an end-to-end task execution within a Linux sandbox environment. Our findings indicate that while GPT-4o leads with a Pass@5 rate surpassing 50%, there remains significant scope for improvement, highlighted by issues such as hallucinated outputs and difficulties with bash script generation. Notably, in the more demanding ML-Agent-Bench, GPT-4o achieves a 76.47% success rate, reflecting the efficacy of iterative action and feedback in complex task resolution.

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

The present paradigm of deep learning models for molecular representation relies mostly on 1D or 2D formats, neglecting significant 3D structural information that offers valuable physical insight. This narrow focus inhibits the model's versatility and adaptability across a wide range of modalities. Conversely, the smaller amount of research that focuses on explicit 3D representation tends to overlook textual data within the biomedical domain. We present a unified pre-trained language model that concurrently captures biomedical text, 2D, and 3D molecular information. Our model (the three-modality molecular language model, MolLM) consists of a text Transformer encoder and a molecular Transformer encoder, which encodes both 2D and 3D molecular structures. Our approach employs contrastive learning as a supervisory signal for cross-modal information learning, and we assemble a multimodality dataset using cheminformatics-based molecular modifications and a wealth of chemical text. MolLM demonstrates robust molecular representation capabilities in numerous downstream tasks, including cross-modality molecule and text matching, property prediction, captioning, and text-prompted editing. Through ablating the 3D functionality of our model, we demonstrate that the inclusion of text, 2D, and 3D representations significantly improves performance on the downstream tasks. Our code, data, and pre-trained model weights are all available at https://github.com/gersteinlab/MolLM.

Pre-trained language models like ChatGPT have significantly improved code generation. As these models scale up, there is an increasing need for the output to handle more intricate tasks. Moreover, in bioinformatics, generating functional programs poses additional notable challenges due to the amount of domain knowledge, the need for complicated data operations, and intricate functional dependencies between the operations. Here, we present BioCoder, a benchmark developed to evaluate existing pre-trained models in generating bioinformatics code. In relation to function-code generation, BioCoder covers potential package dependencies, class declarations, and global variables. It incorporates 1026 functions and 1243 methods in Python and Java from GitHub and 253 examples from the Rosalind Project. BioCoder incorporates a fuzz-testing framework for evaluation, and we have applied it to evaluate many models including InCoder, CodeGen, CodeGen2, SantaCoder, StarCoder, StarCoder+, InstructCodeT5+, and ChatGPT. Our detailed analysis of these models emphasizes the importance of domain knowledge, pragmatic code generation, and contextual understanding. Our dataset, benchmark, Docker images, and scripts required for testing are all available at https://github.com/gersteinlab/biocoder.

Large Language Models (LLMs), despite their remarkable progress across various general domains, encounter significant barriers in medicine and healthcare. This field faces unique challenges such as domain-specific terminologies and the reasoning over specialized knowledge. To address these obstinate issues, we propose a novel Multi-disciplinary Collaboration (MC) framework for the medical domain that leverages role-playing LLM-based agents who participate in a collaborative multi-round discussion, thereby enhancing LLM proficiency and reasoning capabilities. This training-free and interpretable framework encompasses five critical steps: gathering domain experts, proposing individual analyses, summarising these analyses into a report, iterating over discussions until a consensus is reached, and ultimately making a decision. Our work particularly focuses on the zero-shot scenario, our results on nine data sets (MedQA, MedMCQA, PubMedQA, and six subtasks from MMLU) establish that our proposed MC framework excels at mining and harnessing the medical expertise in LLMs, as well as extending its reasoning abilities. Based on these outcomes, we further conduct a human evaluation to pinpoint and categorize common errors within our method, as well as ablation studies aimed at understanding the impact of various factors on overall performance.

Despite the remarkable capabilities of Large Language Models (LLMs) like GPT-4, producing complex, structured tabular data remains challenging. Our study assesses LLMs' proficiency in structuring tables and introduces a novel fine-tuning method, cognizant of data structures, to bolster their performance. We unveil Struc-Bench, a comprehensive benchmark featuring prominent LLMs (GPT-NeoX-20B, GPT-3.5, GPT-4, and Vicuna), which spans text tables, HTML, and LaTeX formats. Our proposed FormatCoT aids in crafting format-specific instructions from the intended outputs to populate this benchmark. Addressing the gap in task-centered evaluation, we propose two innovative metrics, P-Score (Prompting Score) and H-Score (Heuristical Score), to more accurately gauge LLM performance. Our experiments show that applying our structure-aware fine-tuning to LLaMA-7B leads to substantial performance gains, outshining its LLM counterparts across most measures. In-depth error analysis and creating an ability map across six dimensions, coverage, formatting, reasoning, comprehension, pragmatics, and hallucination, highlight areas for future enhancements and suggest forthcoming research trajectories. Our code and models can be found at https://github.com/gersteinlab/Struc-Bench.

Large language models (LLMs) have unveiled remarkable reasoning capabilities by exploiting chain-of-thought (CoT) prompting, which generates intermediate reasoning chains to serve as the rationale for deriving the answer. However, current CoT methods either simply employ general prompts such as Let's think step by step, or heavily rely on handcrafted task-specific demonstrations to attain preferable performances, thereby engendering an inescapable gap between performance and generalization. To bridge this gap, we propose Meta-CoT, a generalizable CoT prompting method in mixed-task scenarios where the type of input questions is unknown. Meta-CoT firstly categorizes the scenario based on the input question and subsequently constructs diverse demonstrations from the corresponding data pool in an automatic pattern. Meta-CoT simultaneously enjoys remarkable performances on ten public benchmark reasoning tasks and superior generalization capabilities. Notably, Meta-CoT achieves the state-of-the-art result on SVAMP (93.7%) without any additional program-aided methods. Our further experiments on five out-of-distribution datasets verify the stability and generality of Meta-CoT.

This paper presents our contribution to the MEDIQA-2023 Dialogue2Note shared task, encompassing both subtask A and subtask B. We approach the task as a dialogue summarization problem and implement two distinct pipelines: (a) a fine-tuning of a pre-trained dialogue summarization model and GPT-3, and (b) few-shot in-context learning (ICL) using a large language model, GPT-4. Both methods achieve excellent results in terms of ROUGE-1 F1, BERTScore F1 (deberta-xlarge-mnli), and BLEURT, with scores of 0.4011, 0.7058, and 0.5421, respectively. Additionally, we predict the associated section headers using RoBERTa and SciBERT based classification models. Our team ranked fourth among all teams, while each team is allowed to submit three runs as part of their submission. We also utilize expert annotations to demonstrate that the notes generated through the ICL GPT-4 are better than all other baselines.