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Jul 6

Embed-Search-Align: DNA Sequence Alignment using Transformer Models

DNA sequence alignment involves assigning short DNA reads to the most probable locations on an extensive reference genome. This process is crucial for various genomic analyses, including variant calling, transcriptomics, and epigenomics. Conventional methods, refined over decades, tackle this challenge in 2 steps: genome indexing followed by efficient search to locate likely positions for given reads. Building on the success of Large Language Models in encoding text into embeddings, where the distance metric captures semantic similarity, recent efforts have explored whether the same Transformer architecture can produce embeddings for DNA sequences. Such models have shown early promise in classifying short DNA sequences, such as detecting coding/non-coding regions, and enhancer, promoter sequences. However, performance at sequence classification tasks does not translate to sequence alignment, where it is necessary to search across the genome to align each read, a significantly longer-range task. We bridge this gap by framing the Sequence Alignment task for Transformer models as an "Embed-Search-Align" task. In this framework, a novel Reference-Free DNA Embedding model generates embeddings of reads and reference fragments, which are projected into a shared vector space where the read-fragment distance is used as a surrogate for alignment. Technical contributions include: (1) Contrastive loss for self-supervised training of DNA sequence representations, facilitating rich reference-free, sequence-level embeddings, and (2) a DNA vector store to enable search across fragments on a global scale. DNA-ESA is 99% accurate when aligning 250-length reads onto a human genome (3gb), rivaling conventional methods such as Bowtie and BWA-Mem. DNA-ESA exceeds the performance of 6 Transformer model baselines such as Nucleotide Transformer, Hyena-DNA, and shows task transfer across chromosomes and species.

  • 8 authors
·
Sep 20, 2023

MAMMAL -- Molecular Aligned Multi-Modal Architecture and Language

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

  • 19 authors
·
Oct 28, 2024 1

Exploring Optimal Transport-Based Multi-Grained Alignments for Text-Molecule Retrieval

The field of bioinformatics has seen significant progress, making the cross-modal text-molecule retrieval task increasingly vital. This task focuses on accurately retrieving molecule structures based on textual descriptions, by effectively aligning textual descriptions and molecules to assist researchers in identifying suitable molecular candidates. However, many existing approaches overlook the details inherent in molecule sub-structures. In this work, we introduce the Optimal TRansport-based Multi-grained Alignments model (ORMA), a novel approach that facilitates multi-grained alignments between textual descriptions and molecules. Our model features a text encoder and a molecule encoder. The text encoder processes textual descriptions to generate both token-level and sentence-level representations, while molecules are modeled as hierarchical heterogeneous graphs, encompassing atom, motif, and molecule nodes to extract representations at these three levels. A key innovation in ORMA is the application of Optimal Transport (OT) to align tokens with motifs, creating multi-token representations that integrate multiple token alignments with their corresponding motifs. Additionally, we employ contrastive learning to refine cross-modal alignments at three distinct scales: token-atom, multitoken-motif, and sentence-molecule, ensuring that the similarities between correctly matched text-molecule pairs are maximized while those of unmatched pairs are minimized. To our knowledge, this is the first attempt to explore alignments at both the motif and multi-token levels. Experimental results on the ChEBI-20 and PCdes datasets demonstrate that ORMA significantly outperforms existing state-of-the-art (SOTA) models.

  • 7 authors
·
Nov 4, 2024

ParEVO: Synthesizing Code for Irregular Data: High-Performance Parallelism through Agentic Evolution

The transition from sequential to parallel computing is essential for modern high-performance applications but is hindered by the steep learning curve of concurrent programming. This challenge is magnified for irregular data structures (such as sparse graphs, unbalanced trees, and non-uniform meshes) where static scheduling fails and data dependencies are unpredictable. Current Large Language Models (LLMs) often fail catastrophically on these tasks, generating code plagued by subtle race conditions, deadlocks, and sub-optimal scaling. We bridge this gap with ParEVO, a framework designed to synthesize high-performance parallel algorithms for irregular data. Our contributions include: (1) The Parlay-Instruct Corpus, a curated dataset of 13,820 tasks synthesized via a "Critic-Refine" pipeline that explicitly filters for empirically performant algorithms that effectively utilize Work-Span parallel primitives; (2) specialized DeepSeek, Qwen, and Gemini models fine-tuned to align probabilistic generation with the rigorous semantics of the ParlayLib library; and (3) an Evolutionary Coding Agent (ECA) that improves the "last mile" of correctness by iteratively repairing code using feedback from compilers, dynamic race detectors, and performance profilers. On the ParEval benchmark, ParEVO achieves an average 106x speedup (with a maximum of 1103x) across the suite, and a robust 13.6x speedup specifically on complex irregular graph problems, outperforming state-of-the-art commercial models. Furthermore, our evolutionary approach matches state-of-the-art expert human baselines, achieving up to a 4.1x speedup on specific highly-irregular kernels. Source code and datasets are available at https://github.com/WildAlg/ParEVO.

BioT5+: Towards Generalized Biological Understanding with IUPAC Integration and Multi-task Tuning

Recent research trends in computational biology have increasingly focused on integrating text and bio-entity modeling, especially in the context of molecules and proteins. However, previous efforts like BioT5 faced challenges in generalizing across diverse tasks and lacked a nuanced understanding of molecular structures, particularly in their textual representations (e.g., IUPAC). This paper introduces BioT5+, an extension of the BioT5 framework, tailored to enhance biological research and drug discovery. BioT5+ incorporates several novel features: integration of IUPAC names for molecular understanding, inclusion of extensive bio-text and molecule data from sources like bioRxiv and PubChem, the multi-task instruction tuning for generality across tasks, and a novel numerical tokenization technique for improved processing of numerical data. These enhancements allow BioT5+ to bridge the gap between molecular representations and their textual descriptions, providing a more holistic understanding of biological entities, and largely improving the grounded reasoning of bio-text and bio-sequences. The model is pre-trained and fine-tuned with a large number of experiments, including 3 types of problems (classification, regression, generation), 15 kinds of tasks, and 21 total benchmark datasets, demonstrating the remarkable performance and state-of-the-art results in most cases. BioT5+ stands out for its ability to capture intricate relationships in biological data, thereby contributing significantly to bioinformatics and computational biology. Our code is available at https://github.com/QizhiPei/BioT5.

  • 9 authors
·
Feb 27, 2024

DEI: Diversity in Evolutionary Inference for Quality-Diversity Search

We present DEI: Diversity in Evolutionary Inference, a distributed Quality-Diversity (QD) search framework that assigns heterogeneous large language models (LLMs) as mutation operators across peer nodes communicating with non-blocking collective operations. Unlike homogeneous parallel search, which replicates a single model's inductive biases across all workers, DEI treats each LLM's distinct creative prior as a complementary source of behavioral novelty. Extending the Digital Red Queen framework with DEI, nodes share local optimal solutions at the end of each round to seed the next round's population. This creates cross-model adversarial pressure that drives robustness beyond intra-model self-play. Evaluated on the Core War domain, a competitive programming benchmark in which Redcode warrior programs battle inside a simulated machine, a four-node heterogeneous ensemble (GPT-5.4-mini, Claude Sonnet 4.6, GPT-5.2, and Claude Haiku 4.5) achieves 124 percent higher merged-archive QD-Score (45.90 vs. 20.46) and 28 percent higher coverage (80.6 percent vs. 63.0 percent of cells) than a single-node baseline at equal total LLM-call budget. The heterogeneous ensemble also outperforms an equally-budgeted homogeneous ensemble on QD-Score, coverage, and held-out solution generality across all four model families. These results provide the first empirical evidence that model diversity, not merely parallelism, is the key driver of gain in distributed LLM-based QD search.

Gensyn Gensyn
·
May 25 2

A large collection of bioinformatics question-query pairs over federated knowledge graphs: methodology and applications

Background. In the last decades, several life science resources have structured data using the same framework and made these accessible using the same query language to facilitate interoperability. Knowledge graphs have seen increased adoption in bioinformatics due to their advantages for representing data in a generic graph format. For example, yummydata.org catalogs more than 60 knowledge graphs accessible through SPARQL, a technical query language. Although SPARQL allows powerful, expressive queries, even across physically distributed knowledge graphs, formulating such queries is a challenge for most users. Therefore, to guide users in retrieving the relevant data, many of these resources provide representative examples. These examples can also be an important source of information for machine learning, if a sufficiently large number of examples are provided and published in a common, machine-readable and standardized format across different resources. Findings. We introduce a large collection of human-written natural language questions and their corresponding SPARQL queries over federated bioinformatics knowledge graphs (KGs) collected for several years across different research groups at the SIB Swiss Institute of Bioinformatics. The collection comprises more than 1000 example questions and queries, including 65 federated queries. We propose a methodology to uniformly represent the examples with minimal metadata, based on existing standards. Furthermore, we introduce an extensive set of open-source applications, including query graph visualizations and smart query editors, easily reusable by KG maintainers who adopt the proposed methodology. Conclusions. We encourage the community to adopt and extend the proposed methodology, towards richer KG metadata and improved Semantic Web services.

  • 17 authors
·
Oct 8, 2024

Contrastive Learning and Mixture of Experts Enables Precise Vector Embeddings

The advancement of transformer neural networks has significantly elevated the capabilities of sentence similarity models, particularly in creating effective vector representations of natural language inputs. However, these models face notable challenges in domain-specific contexts, especially in highly specialized scientific sub-fields. Traditional methods often struggle in this regime, either overgeneralizing similarities within a niche or being overly sensitive to minor differences, resulting in inaccurate text classification and subpar vector representation. In an era where retrieval augmentation and search are increasingly crucial, precise and concise numerical representations are essential. In this paper, we target this issue by assembling niche datasets using co-citations as a similarity metric, focusing on biomedical domains. We employ two key strategies for fine-tuning state-of-the-art models: 1. Domain-specific Fine-Tuning, which tailors pretrained models to a single domain, and 2. Universal Applicability with Mixture of Experts (MoE), adapting pretrained models with enforced routing for multiple domains simultaneously. Our training approach emphasizes the use of abstracts for faster training, incorporating Multiple Negative Rankings loss for efficient contrastive learning. Notably, our MoE variants, equipped with N experts, achieve the efficacy of N individual models, heralding a new era of versatile, One-Size-Fits-All transformer networks for various tasks. This methodology marks significant advancements in scientific text classification metrics and holds promise for enhancing vector database search and compilation.

  • 4 authors
·
Jan 28, 2024

vstash: Local-First Hybrid Retrieval with Adaptive Fusion for LLM Agents

We present **vstash**, a local-first document memory system that combines vector similarity search with full-text keyword matching via Reciprocal Rank Fusion (RRF) and adaptive per-query IDF weighting. All data resides in a single SQLite file using sqlite-vec for approximate nearest neighbor search and FTS5 for keyword matching. We make four primary contributions. **(1)** Self-supervised embedding refinement via hybrid retrieval disagreement: across 753 BEIR queries on SciFact, NFCorpus, and FiQA, 74.5% produce top-10 disagreement between vector-heavy (vec=0.95, fts=0.05) and FTS-heavy (vec=0.05, fts=0.95) search (per-dataset rates 63.4% / 73.4% / 86.7%, Section 5.2), providing a free training signal without human labels. Fine-tuning BGE-small (33M params) with MultipleNegativesRankingLoss on 76K disagreement triples improves NDCG@10 on all 5 BEIR datasets (up to +19.5% on NFCorpus vs. BGE-small base RRF, Table 6). On 3 of 5 datasets, under different preprocessing, the tuned 33M-parameter pipeline matches or exceeds published ColBERTv2 results (110M params) and an untrained BGE-base (110M); on FiQA and ArguAna it underperforms ColBERTv2 (Section 5.5). **(2)** Adaptive RRF with per-query IDF weighting improves NDCG@10 on all 5 BEIR datasets versus fixed weights (up to +21.4% on ArguAna), achieving 0.7263 on SciFact with BGE-small. **(3)** A negative result on post-RRF scoring: frequency+decay, history-augmented recall, and cross-encoder reranking all failed to improve NDCG. **(4)** A production-grade substrate with integrity checking, schema versioning, ranking diagnostics, and a distance-based relevance signal validated on 50,425 relevance-judged queries across the 5 BEIR datasets. Search latency remains 20.9 ms median at 50K chunks with stable NDCG. The fine-tuned model is published as `Stffens/bge-small-rrf-v2` on HuggingFace. All code, data, and experiments are open-source.

  • 1 authors
·
Apr 15

DSGym: A Holistic Framework for Evaluating and Training Data Science Agents

Data science agents promise to accelerate discovery and insight-generation by turning data into executable analyses and findings. Yet existing data science benchmarks fall short due to fragmented evaluation interfaces that make cross-benchmark comparison difficult, narrow task coverage and a lack of rigorous data grounding. In particular, we show that a substantial portion of tasks in current benchmarks can be solved without using the actual data. To address these limitations, we introduce DSGym, a standardized framework for evaluating and training data science agents in self-contained execution environments. Unlike static benchmarks, DSGym provides a modular architecture that makes it easy to add tasks, agent scaffolds, and tools, positioning it as a live, extensible testbed. We curate DSGym-Tasks, a holistic task suite that standardizes and refines existing benchmarks via quality and shortcut solvability filtering. We further expand coverage with (1) DSBio: expert-derived bioinformatics tasks grounded in literature and (2) DSPredict: challenging prediction tasks spanning domains such as computer vision, molecular prediction, and single-cell perturbation. Beyond evaluation, DSGym enables agent training via execution-verified data synthesis pipeline. As a case study, we build a 2,000-example training set and trained a 4B model in DSGym that outperforms GPT-4o on standardized analysis benchmarks. Overall, DSGym enables rigorous end-to-end measurement of whether agents can plan, implement, and validate data analyses in realistic scientific context.

  • 9 authors
·
Jan 22 2

Samanantar: The Largest Publicly Available Parallel Corpora Collection for 11 Indic Languages

We present Samanantar, the largest publicly available parallel corpora collection for Indic languages. The collection contains a total of 49.7 million sentence pairs between English and 11 Indic languages (from two language families). Specifically, we compile 12.4 million sentence pairs from existing, publicly-available parallel corpora, and additionally mine 37.4 million sentence pairs from the web, resulting in a 4x increase. We mine the parallel sentences from the web by combining many corpora, tools, and methods: (a) web-crawled monolingual corpora, (b) document OCR for extracting sentences from scanned documents, (c) multilingual representation models for aligning sentences, and (d) approximate nearest neighbor search for searching in a large collection of sentences. Human evaluation of samples from the newly mined corpora validate the high quality of the parallel sentences across 11 languages. Further, we extract 83.4 million sentence pairs between all 55 Indic language pairs from the English-centric parallel corpus using English as the pivot language. We trained multilingual NMT models spanning all these languages on Samanantar, which outperform existing models and baselines on publicly available benchmarks, such as FLORES, establishing the utility of Samanantar. Our data and models are available publicly at https://indicnlp.ai4bharat.org/samanantar/ and we hope they will help advance research in NMT and multilingual NLP for Indic languages.

  • 18 authors
·
Apr 12, 2021

Aligning Multimodal LLM with Human Preference: A Survey

Large language models (LLMs) can handle a wide variety of general tasks with simple prompts, without the need for task-specific training. Multimodal Large Language Models (MLLMs), built upon LLMs, have demonstrated impressive potential in tackling complex tasks involving visual, auditory, and textual data. However, critical issues related to truthfulness, safety, o1-like reasoning, and alignment with human preference remain insufficiently addressed. This gap has spurred the emergence of various alignment algorithms, each targeting different application scenarios and optimization goals. Recent studies have shown that alignment algorithms are a powerful approach to resolving the aforementioned challenges. In this paper, we aim to provide a comprehensive and systematic review of alignment algorithms for MLLMs. Specifically, we explore four key aspects: (1) the application scenarios covered by alignment algorithms, including general image understanding, multi-image, video, and audio, and extended multimodal applications; (2) the core factors in constructing alignment datasets, including data sources, model responses, and preference annotations; (3) the benchmarks used to evaluate alignment algorithms; and (4) a discussion of potential future directions for the development of alignment algorithms. This work seeks to help researchers organize current advancements in the field and inspire better alignment methods. The project page of this paper is available at https://github.com/BradyFU/Awesome-Multimodal-Large-Language-Models/tree/Alignment.

  • 17 authors
·
Mar 18, 2025 3

Zeppelin: Balancing Variable-length Workloads in Data Parallel Large Model Training

Training large language models (LLMs) with increasingly long and varying sequence lengths introduces severe load imbalance challenges in large-scale data-parallel training. Recent frameworks attempt to mitigate these issues through data reorganization or hybrid parallel strategies. However, they often overlook how computational and communication costs scale with sequence length, resulting in suboptimal performance. We identify three critical challenges: (1) varying computation-to-communication ratios across sequences of different lengths in distributed attention, (2) mismatch between static NIC-GPU affinity and dynamic parallel workloads, and (3) distinct optimal partitioning strategies required for quadratic attention versus linear components. To address these challenges, we present Zeppelin, a novel training system that integrates three key techniques: (1) a hierarchical sequence partitioning method for the attention module that reduces communication overhead and balances computation, supported by an efficient attention engine that applies divergent parallel strategies; (2) a routing layer that orchestrates inter-node transfers to fully utilize NIC bandwidth; and (3) a remapping layer that transforms sequence layouts between attention and linear modules, ensuring high computational efficiency across both. Comprehensive evaluations across diverse configurations show that Zeppelin delivers an average 2.80x speedup over state-of-the-art methods.

  • 10 authors
·
Sep 26, 2025

Dynamic Expert Sharing: Decoupling Memory from Parallelism in Mixture-of-Experts Diffusion LLMs

Among parallel decoding paradigms, diffusion large language models (dLLMs) have emerged as a promising candidate that balances generation quality and throughput. However, their integration with Mixture-of-Experts (MoE) architectures is constrained by an expert explosion: as the number of tokens generated in parallel increases, the number of distinct experts activated grows nearly linearly. This results in substantial memory traffic that pushes inference into a memory-bound regime, negating the efficiency gains of both MoE and parallel decoding. To address this challenge, we propose Dynamic Expert Sharing (DES), a novel technique that shifts MoE optimization from token-centric pruning and conventional expert skipping methods to sequence-level coreset selection. To maximize expert reuse, DES identifies a compact, high-utility set of experts to satisfy the requirements of an entire parallel decoding block. We introduce two innovative selection strategies: (1) Intra-Sequence Sharing (DES-Seq), which adapts optimal allocation to the sequence level, and (2) Saliency-Aware Voting (DES-Vote), a novel mechanism that allows tokens to collectively elect a coreset based on aggregated router weights. Extensive experiments on MoE dLLMs demonstrate that DES reduces unique expert activations by over 55% and latency by up to 38%, while retaining 99% of vanilla accuracy, effectively decoupling memory overhead from the degree of parallelism.

  • 9 authors
·
Jan 30

ZIP-FIT: Embedding-Free Data Selection via Compression-Based Alignment

Data selection is crucial for optimizing language model (LM) performance on specific tasks, yet most existing methods fail to effectively consider the target task distribution. Current approaches either ignore task-specific requirements entirely or rely on approximations that fail to capture the nuanced patterns needed for tasks like Autoformalization or code generation. Methods that do consider the target distribution often rely on simplistic, sometimes noisy, representations, like hashed n-gram features, which can lead to collisions and introduce noise. We introduce ZIP-FIT, a data selection framework that uses gzip compression to directly measure alignment between potential training data and the target task distribution. In extensive evaluations on Autoformalization and Python code generation, ZIP-FIT significantly outperforms leading baselines like DSIR and D4. Models trained on ZIP-FIT-selected data achieve their lowest cross-entropy loss up to 85.1\% faster than baselines, demonstrating that better task alignment leads to more efficient learning. In addition, ZIP-FIT performs selection up to 65.8\% faster than DSIR and two orders of magnitude faster than D4. Notably, ZIP-FIT shows that smaller, well-aligned datasets often outperform larger but less targeted ones, demonstrating that a small amount of higher quality data is superior to a large amount of lower quality data. Our results imply that task-aware data selection is crucial for efficient domain adaptation, and that compression offers a principled way to measure task alignment. By showing that targeted data selection can dramatically improve task-specific performance, our work provides new insights into the relationship between data quality, task alignment, and model learning efficiency.

  • 7 authors
·
Oct 23, 2024 2

GeneGPT: Augmenting Large Language Models with Domain Tools for Improved Access to Biomedical Information

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

  • 4 authors
·
Apr 19, 2023

Omni-DNA: A Unified Genomic Foundation Model for Cross-Modal and Multi-Task Learning

Large Language Models (LLMs) demonstrate remarkable generalizability across diverse tasks, yet genomic foundation models (GFMs) still require separate finetuning for each downstream application, creating significant overhead as model sizes grow. Moreover, existing GFMs are constrained by rigid output formats, limiting their applicability to various genomic tasks. In this work, we revisit the transformer-based auto-regressive models and introduce Omni-DNA, a family of cross-modal multi-task models ranging from 20 million to 1 billion parameters. Our approach consists of two stages: (i) pretraining on DNA sequences with next token prediction objective, and (ii) expanding the multi-modal task-specific tokens and finetuning for multiple downstream tasks simultaneously. When evaluated on the Nucleotide Transformer and GB benchmarks, Omni-DNA achieves state-of-the-art performance on 18 out of 26 tasks. Through multi-task finetuning, Omni-DNA addresses 10 acetylation and methylation tasks at once, surpassing models trained on each task individually. Finally, we design two complex genomic tasks, DNA2Function and Needle-in-DNA, which map DNA sequences to textual functional descriptions and images, respectively, indicating Omni-DNA's cross-modal capabilities to broaden the scope of genomic applications. All the models are available through https://huggingface.co/collections/zehui127

  • 7 authors
·
Feb 5, 2025

Does your model understand genes? A benchmark of gene properties for biological and text models

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

  • 5 authors
·
Dec 5, 2024

Prot2Token: A Unified Framework for Protein Modeling via Next-Token Prediction

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 .

  • 9 authors
·
May 26, 2025 2

Infini-gram mini: Exact n-gram Search at the Internet Scale with FM-Index

Language models are trained mainly on massive text data from the Internet, and it becomes increasingly important to understand this data source. Exact-match search engines enable searching in large text corpora -- counting string appearances and retrieving the enclosing documents -- yet the high storage overhead hinders their application on Internet-scale data. We present Infini-gram mini, an efficient and scalable system that can make petabyte-level text corpora searchable. Based on the FM-index data structure (Ferragina and Manzini, 2000), which simultaneously indexes and compresses text, our system creates indexes with size only 44% of the corpus. Infini-gram mini greatly improves upon the best existing implementation of FM-index in terms of indexing speed (18times) and memory use during both indexing (3.2times reduction) and querying (down to a negligible amount). We index 46TB of Internet text in 50 days with a single 128-core CPU node (or 19 hours if using 75 such nodes). We show one important use case of Infini-gram mini in a large-scale analysis of benchmark contamination. We find several core LM evaluation benchmarks to be heavily contaminated in Internet crawls (up to 40% in SQuAD), which could lead to overestimating the capabilities of language models if trained on such data. We host a benchmark contamination bulletin to share the contamination rate of many core and community-contributed benchmarks. We also release a web interface and an API endpoint to serve general search queries on Infini-gram mini indexes.

  • 5 authors
·
Jun 13, 2025 3

When Life Gives You Samples: The Benefits of Scaling up Inference Compute for Multilingual LLMs

Recent advancements in large language models (LLMs) have shifted focus toward scaling inference-time compute, improving performance without retraining the model. A common approach is to sample multiple outputs in parallel, and select one of these as the final output. However, work to date has focused on English and a handful of domains such as math and code. In contrast, we are most interested in techniques that generalize across open-ended tasks, formally verifiable tasks, and across languages. In this work, we study how to robustly scale inference-time compute for open-ended generative tasks in a multilingual, multi-task setting. Our findings show that both sampling strategy based on temperature variation and selection strategy must be adapted to account for diverse domains and varied language settings. We evaluate existing selection methods, revealing that strategies effective in English often fail to generalize across languages. We propose novel sampling and selection strategies specifically adapted for multilingual and multi-task inference scenarios, and show they yield notable gains across languages and tasks. In particular, our combined sampling and selection methods lead to an average +6.8 jump in win-rates for our 8B models on m-ArenaHard-v2.0 prompts, against proprietary models such as Gemini. At larger scale, Command-A (111B model) equipped with our methods, shows +9.0 improvement in win-rates on the same benchmark with just five samples against single-sample decoding, a substantial increase at minimal cost. Our results underscore the need for language- and task-aware approaches to inference-time compute, aiming to democratize performance improvements in underrepresented languages.

  • 5 authors
·
Jun 25, 2025 1

MMTEB: Massive Multilingual Text Embedding Benchmark

Text embeddings are typically evaluated on a limited set of tasks, which are constrained by language, domain, and task diversity. To address these limitations and provide a more comprehensive evaluation, we introduce the Massive Multilingual Text Embedding Benchmark (MMTEB) - a large-scale, community-driven expansion of MTEB, covering over 500 quality-controlled evaluation tasks across 250+ languages. MMTEB includes a diverse set of challenging, novel tasks such as instruction following, long-document retrieval, and code retrieval, representing the largest multilingual collection of evaluation tasks for embedding models to date. Using this collection, we develop several highly multilingual benchmarks, which we use to evaluate a representative set of models. We find that while large language models (LLMs) with billions of parameters can achieve state-of-the-art performance on certain language subsets and task categories, the best-performing publicly available model is multilingual-e5-large-instruct with only 560 million parameters. To facilitate accessibility and reduce computational cost, we introduce a novel downsampling method based on inter-task correlation, ensuring a diverse selection while preserving relative model rankings. Furthermore, we optimize tasks such as retrieval by sampling hard negatives, creating smaller but effective splits. These optimizations allow us to introduce benchmarks that drastically reduce computational demands. For instance, our newly introduced zero-shot English benchmark maintains a ranking order similar to the full-scale version but at a fraction of the computational cost.

BioMatrix: Towards a Comprehensive Biological Foundation Model Spanning the Modality Matrix of Sequences, Structures, and Language

We present BioMatrix, the first multimodal foundation model that natively integrates sequences, structures, and natural language for both molecules and proteins within a single decoder-only architecture. Existing biological foundation models pursue native multimodality and broad entity coverage separately: those that fuse multiple modalities under a shared objective remain confined to a single entity type, while those spanning multiple entity types either omit explicit structural modeling or rely on adapter-based designs in which the model cannot natively generate the very modalities it can read. BioMatrix closes this gap by mapping molecular sequences (supporting both SMILES and SELFIES notations), molecular structures, protein sequences, protein structures, and natural language into a shared discrete token space through a unified tokenization scheme, so that all modalities are consumed and produced uniformly under a single next-token prediction objective -- without external encoders, projection adapters, or modality-specific output heads. Built upon the Qwen3 language model (1.7B and 4B), BioMatrix is continually pretrained on 304.4 billion tokens spanning general and domain-specific text, sequence and structure views of molecules and proteins, and cross-modal corpora that interleave biomolecular entities with scientific text and link distinct entities through molecule-protein and protein-protein interaction data. After tuning on a comprehensive suite of downstream applications covering 80 tasks across 6 categories -- encompassing single-entity and multi-entity understanding and generation tasks across and within modalities -- BioMatrix achieves state-of-the-art or competitive performance on 77 out of 80 tasks, demonstrating that a single, natively multimodal generalist model can effectively match or surpass specialized approaches across a wide range of biological tasks.

optimize_anything: A Universal API for Optimizing any Text Parameter

Can a single LLM-based optimization system match specialized tools across fundamentally different domains? We show that when optimization problems are formulated as improving a text artifact evaluated by a scoring function, a single AI-based optimization system-supporting single-task search, multi-task search with cross-problem transfer, and generalization to unseen inputs-achieves state-of-the-art results across six diverse tasks. Our system discovers agent architectures that nearly triple Gemini Flash's ARC-AGI accuracy (32.5% to 89.5%), finds scheduling algorithms that cut cloud costs by 40%, generates CUDA kernels where 87% match or beat PyTorch, and outperforms AlphaEvolve's reported circle packing solution (n=26). Ablations across three domains reveal that actionable side information yields faster convergence and substantially higher final scores than score-only feedback, and that multi-task search outperforms independent optimization given equivalent per-problem budget through cross-task transfer, with benefits scaling with the number of related tasks. Together, we show for the first time that text optimization with LLM-based search is a general-purpose problem-solving paradigm, unifying tasks traditionally requiring domain-specific algorithms under a single framework. We open-source optimize\_anything with support for multiple backends as part of the GEPA project at https://github.com/gepa-ai/gepa .

  • 14 authors
·
May 18 1

Find Central Dogma Again

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.

  • 1 authors
·
Feb 10, 2025

Planning In Natural Language Improves LLM Search For Code Generation

While scaling training compute has led to remarkable improvements in large language models (LLMs), scaling inference compute has not yet yielded analogous gains. We hypothesize that a core missing component is a lack of diverse LLM outputs, leading to inefficient search due to models repeatedly sampling highly similar, yet incorrect generations. We empirically demonstrate that this lack of diversity can be mitigated by searching over candidate plans for solving a problem in natural language. Based on this insight, we propose PLANSEARCH, a novel search algorithm which shows strong results across HumanEval+, MBPP+, and LiveCodeBench (a contamination-free benchmark for competitive coding). PLANSEARCH generates a diverse set of observations about the problem and then uses these observations to construct plans for solving the problem. By searching over plans in natural language rather than directly over code solutions, PLANSEARCH explores a significantly more diverse range of potential solutions compared to baseline search methods. Using PLANSEARCH on top of Claude 3.5 Sonnet achieves a state-of-the-art pass@200 of 77.0% on LiveCodeBench, outperforming both the best score achieved without search (pass@1 = 41.4%) and using standard repeated sampling (pass@200 = 60.6%). Finally, we show that, across all models, search algorithms, and benchmarks analyzed, we can accurately predict performance gains due to search as a direct function of the diversity over generated ideas.

  • 10 authors
·
Sep 5, 2024 1

In-BoXBART: Get Instructions into Biomedical Multi-Task Learning

Single-task models have proven pivotal in solving specific tasks; however, they have limitations in real-world applications where multi-tasking is necessary and domain shifts are exhibited. Recently, instructional prompts have shown significant improvement towards multi-task generalization; however, the effect of instructional prompts and Multi-Task Learning (MTL) has not been systematically studied in the biomedical domain. Motivated by this, this paper explores the impact of instructional prompts for biomedical MTL. We introduce the BoX, a collection of 32 instruction tasks for Biomedical NLP across (X) various categories. Using this meta-dataset, we propose a unified model termed In-BoXBART, that can jointly learn all tasks of the BoX without any task-specific modules. To the best of our knowledge, this is the first attempt to propose a unified model in the biomedical domain and use instructions to achieve generalization across several biomedical tasks. Experimental results indicate that the proposed model: 1) outperforms the single-task baseline by ~3% and multi-task (without instruction) baseline by ~18% on an average, and 2) shows ~23% improvement compared to the single-task baseline in few-shot learning (i.e., 32 instances per task) on an average. Our analysis indicates that there is significant room for improvement across tasks in the BoX, implying the scope for future research direction.

  • 6 authors
·
Apr 15, 2022

DNABERT-2: Efficient Foundation Model and Benchmark For Multi-Species Genome

Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates 28 distinct datasets across 7 tasks, with input lengths ranging from 70 to 1000. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with 21 times fewer parameters and approximately 56 times less GPU time in pre-training.

  • 6 authors
·
Jun 26, 2023

CoIR: A Comprehensive Benchmark for Code Information Retrieval Models

Despite the substantial success of Information Retrieval (IR) in various NLP tasks, most IR systems predominantly handle queries and corpora in natural language, neglecting the domain of code retrieval. Code retrieval is critically important yet remains under-explored, with existing methods and benchmarks inadequately representing the diversity of code in various domains and tasks. Addressing this gap, we present \name (Code Information Retrieval Benchmark), a robust and comprehensive benchmark specifically designed to assess code retrieval capabilities. \name comprises ten meticulously curated code datasets, spanning eight distinctive retrieval tasks across seven diverse domains. We first discuss the construction of \name and its diverse dataset composition. Further, we evaluate nine widely used retrieval models using \name, uncovering significant difficulties in performing code retrieval tasks even with state-of-the-art systems. To facilitate easy adoption and integration within existing research workflows, \name has been developed as a user-friendly Python framework, readily installable via pip. It shares same data schema as other popular benchmarks like MTEB and BEIR, enabling seamless cross-benchmark evaluations. Through \name, we aim to invigorate research in the code retrieval domain, providing a versatile benchmarking tool that encourages further development and exploration of code retrieval systems\url{ https://github.com/CoIR-team/coir}.

  • 9 authors
·
Jul 3, 2024

Mixture-of-Instructions: Comprehensive Alignment of a Large Language Model through the Mixture of Diverse System Prompting Instructions

With the proliferation of large language models (LLMs), the comprehensive alignment of such models across multiple tasks has emerged as a critical area of research. Existing alignment methodologies primarily address single task, such as multi-turn dialogue, coding, mathematical problem-solving, and tool usage. However, AI-driven products that leverage language models usually necessitate a fusion of these abilities to function effectively in real-world scenarios. Moreover, the considerable computational resources required for proper alignment of LLMs underscore the need for a more robust, efficient, and encompassing approach to multi-task alignment, ensuring improved generative performance. In response to these challenges, we introduce a novel technique termed Mixture-of-Instructions (MoI), which employs a strategy of instruction concatenation combined with diverse system prompts to boost the alignment efficiency of language models. We have also compiled a diverse set of seven benchmark datasets to rigorously evaluate the alignment efficacy of the MoI-enhanced language model. Our methodology was applied to the open-source Qwen-7B-chat model, culminating in the development of Qwen-SFT-MoI. This enhanced model demonstrates significant advancements in generative capabilities across coding, mathematics, and tool use tasks.

  • 4 authors
·
Apr 28, 2024

Bilingual Corpus Mining and Multistage Fine-Tuning for Improving Machine Translation of Lecture Transcripts

Lecture transcript translation helps learners understand online courses, however, building a high-quality lecture machine translation system lacks publicly available parallel corpora. To address this, we examine a framework for parallel corpus mining, which provides a quick and effective way to mine a parallel corpus from publicly available lectures on Coursera. To create the parallel corpora, we propose a dynamic programming based sentence alignment algorithm which leverages the cosine similarity of machine-translated sentences. The sentence alignment F1 score reaches 96%, which is higher than using the BERTScore, LASER, or sentBERT methods. For both English--Japanese and English--Chinese lecture translations, we extracted parallel corpora of approximately 50,000 lines and created development and test sets through manual filtering for benchmarking translation performance. Through machine translation experiments, we show that the mined corpora enhance the quality of lecture transcript translation when used in conjunction with out-of-domain parallel corpora via multistage fine-tuning. Furthermore, this study also suggests guidelines for gathering and cleaning corpora, mining parallel sentences, cleaning noise in the mined data, and creating high-quality evaluation splits. For the sake of reproducibility, we have released the corpora as well as the code to create them. The dataset is available at https://github.com/shyyhs/CourseraParallelCorpusMining.

  • 5 authors
·
Nov 6, 2023

LLM as Dataset Analyst: Subpopulation Structure Discovery with Large Language Model

The distribution of subpopulations is an important property hidden within a dataset. Uncovering and analyzing the subpopulation distribution within datasets provides a comprehensive understanding of the datasets, standing as a powerful tool beneficial to various downstream tasks, including Dataset Subpopulation Organization, Subpopulation Shift, and Slice Discovery. Despite its importance, there has been no work that systematically explores the subpopulation distribution of datasets to our knowledge. To address the limitation and solve all the mentioned tasks in a unified way, we introduce a novel concept of subpopulation structures to represent, analyze, and utilize subpopulation distributions within datasets. To characterize the structures in an interpretable manner, we propose the Subpopulation Structure Discovery with Large Language Models (SSD-LLM) framework, which employs world knowledge and instruction-following capabilities of Large Language Models (LLMs) to linguistically analyze informative image captions and summarize the structures. Furthermore, we propose complete workflows to address downstream tasks, named Task-specific Tuning, showcasing the application of the discovered structure to a spectrum of subpopulation-related tasks, including dataset subpopulation organization, subpopulation shift, and slice discovery. Furthermore, we propose complete workflows to address downstream tasks, named Task-specific Tuning, showcasing the application of the discovered structure to a spectrum of subpopulation-related tasks, including dataset subpopulation organization, subpopulation shift, and slice discovery.

  • 6 authors
·
May 3, 2024

REDSearcher: A Scalable and Cost-Efficient Framework for Long-Horizon Search Agents

Large language models are transitioning from generalpurpose knowledge engines to realworld problem solvers, yet optimizing them for deep search tasks remains challenging. The central bottleneck lies in the extreme sparsity of highquality search trajectories and reward signals, arising from the difficulty of scalable longhorizon task construction and the high cost of interactionheavy rollouts involving external tool calls. To address these challenges, we propose REDSearcher, a unified framework that codesigns complex task synthesis, midtraining, and posttraining for scalable searchagent optimization. Specifically, REDSearcher introduces the following improvements: (1) We frame task synthesis as a dualconstrained optimization, where task difficulty is precisely governed by graph topology and evidence dispersion, allowing scalable generation of complex, highquality tasks. (2) We introduce toolaugmented queries to encourage proactive tool use rather than passive recall.(3) During midtraining, we strengthen core atomic capabilities knowledge, planning, and function calling substantially reducing the cost of collecting highquality trajectories for downstream training. (4) We build a local simulated environment that enables rapid, lowcost algorithmic iteration for reinforcement learning experiments. Across both textonly and multimodal searchagent benchmarks, our approach achieves stateoftheart performance. To facilitate future research on longhorizon search agents, we will release 10K highquality complex text search trajectories, 5K multimodal trajectories and 1K text RL query set, and together with code and model checkpoints.

MEXA: Multilingual Evaluation of English-Centric LLMs via Cross-Lingual Alignment

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.

cis-lmu CIS, LMU Munich
·
Oct 8, 2024 2

GenomeQA: Benchmarking General Large Language Models for Genome Sequence Understanding

Large Language Models (LLMs) are increasingly adopted as conversational assistants in genomics, where they are mainly used to reason over biological knowledge, annotations, and analysis outputs through natural language interfaces. However, existing benchmarks either focus on specialized DNA models trained for sequence prediction or evaluate biological knowledge using text-only questions, leaving the behavior of general-purpose LLMs when directly exposed to raw genome sequences underexplored. We introduce GenomeQA, a benchmark designed to provide a controlled evaluation setting for general-purpose LLMs on sequence-based genome inference tasks. GenomeQA comprises 5,200 samples drawn from multiple biological databases, with sequence lengths ranging from 6 to 1,000 base pairs (bp), spanning six task families: Enhancer and Promoter Identification, Splice Site Identification, Taxonomic Classification, Histone Mark Prediction, Transcription Factor Binding Site Prediction, and TF Motif Prediction. Across six frontier LLMs, we find that models consistently outperform random baselines and can exploit local sequence signals such as GC content and short motifs, while performance degrades on tasks that require more indirect or multi-step inference over sequence patterns. GenomeQA establishes a diagnostic benchmark for studying and improving the use of general-purpose LLMs on raw genomic sequences.

  • 7 authors
·
Apr 6

BioProBench: Comprehensive Dataset and Benchmark in Biological Protocol Understanding and Reasoning

Biological protocols are fundamental to reproducible and safe life science research. While LLMs excel on general tasks, their systematic evaluation on these highly specialized, accuracy-critical, and inherently procedural texts remains limited. In this work, we present BioProBench, the first large-scale, integrated multi-task benchmark for biological protocol understanding and reasoning. While limited benchmarks have touched upon specific aspects like protocol QA, BioProBench provides a comprehensive suite of five core tasks: Protocol Question Answering, Step Ordering, Error Correction, Protocol Generation, and Protocol Reasoning, enabling a holistic evaluation of LLMs on procedural biological texts. Built upon 27K original protocols, it yields nearly 556K high-quality structured instances. We evaluate 12 mainstream open/closed-source LLMs on BioProBench. Experimental results reveal that while top models preform well on surface understanding tasks, struggle significantly with deep reasoning and structured generation tasks like ordering and generation. Furthermore, model comparisons reveal diverse performance: certain open-source models approach closed-source levels on some tasks, yet bio-specific small models lag behind general LLMs, indicating limitations on complex procedural content. Overall, our findings underscore that procedural reasoning within biological protocols represents a significant challenge for current LLMs. BioProBench serves as a standardized framework to diagnose these specific limitations and guide the development of AI systems better equipped for safely automating complex scientific procedures. The code and data are available at: https://github.com/YuyangSunshine/bioprotocolbench and https://huggingface.co/datasets/GreatCaptainNemo/BioProBench.

  • 5 authors
·
May 11, 2025

Generalizing Test-time Compute-optimal Scaling as an Optimizable Graph

Test-Time Scaling (TTS) improves large language models (LLMs) by allocating additional computation during inference, typically through parallel, sequential, or hybrid scaling. However, prior studies often assume fixed collaboration architectures (e.g., topologies) and single-model usage, overlooking that optimal architectures and model combinations can vary across tasks. Therefore, we study the novel problem of searching for compute-optimal model combinations and architectures in TTS under a fixed budget. We formalize it as a multi-LLM collaboration graph, where nodes encode roles and LLM model assignments, and edges capture information flow. This problem is challenging because (i) the combinatorial search space is prohibitively large, and (ii) task-specific requirements demand tailored designs. To address these, we reformulate the problem as probabilistic graph optimization and, through pilot experiments, derive three empirical insights into TTS collaboration graphs. Guided by these insights, we propose Agent-REINFORCE, an LLM-agent-augmented framework that mirrors the REINFORCE pipeline by mapping sampling-gradient-update to sampling-feedback-update, where feedback serves as a textual gradient to update the probabilistic graph and efficiently search for optimal multi-LLM collaboration graphs. Experiments show that Agent-REINFORCE outperforms both traditional and LLM-based baselines in sample efficiency and search performance, and effectively identifies optimal graphs under joint objectives of accuracy and inference latency.

Evaluating Protein Transfer Learning with TAPE

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.

  • 8 authors
·
Jun 19, 2019

DiscoveryBench: Towards Data-Driven Discovery with Large Language Models

Can the rapid advances in code generation, function calling, and data analysis using large language models (LLMs) help automate the search and verification of hypotheses purely from a set of provided datasets? To evaluate this question, we present DiscoveryBench, the first comprehensive benchmark that formalizes the multi-step process of data-driven discovery. The benchmark is designed to systematically assess current model capabilities in discovery tasks and provide a useful resource for improving them. Our benchmark contains 264 tasks collected across 6 diverse domains, such as sociology and engineering, by manually deriving discovery workflows from published papers to approximate the real-world challenges faced by researchers, where each task is defined by a dataset, its metadata, and a discovery goal in natural language. We additionally provide 903 synthetic tasks to conduct controlled evaluations across task complexity. Furthermore, our structured formalism of data-driven discovery enables a facet-based evaluation that provides useful insights into different failure modes. We evaluate several popular LLM-based reasoning frameworks using both open and closed LLMs as baselines on DiscoveryBench and find that even the best system scores only 25%. Our benchmark, thus, illustrates the challenges in autonomous data-driven discovery and serves as a valuable resource for the community to make progress.

  • 10 authors
·
Jul 1, 2024

RAGRouter-Bench: A Dataset and Benchmark for Adaptive RAG Routing

Retrieval-Augmented Generation (RAG) has become a core paradigm for grounding large language models with external knowledge. Despite extensive efforts exploring diverse retrieval strategies, existing studies predominantly focus on query-side complexity or isolated method improvements, lacking a systematic understanding of how RAG paradigms behave across different query-corpus contexts and effectiveness-efficiency trade-offs. In this work, we introduce RAGRouter-Bench, the first dataset and benchmark designed for adaptive RAG routing. RAGRouter-Bench revisits retrieval from a query-corpus compatibility perspective and standardizes five representative RAG paradigms for systematic evaluation across 7,727 queries and 21,460 documents spanning diverse domains. The benchmark incorporates three canonical query types together with fine-grained semantic and structural corpus metrics, as well as a unified evaluation for both generation quality and resource consumption. Experiments with DeepSeek-V3 and LLaMA-3.1-8B demonstrate that no single RAG paradigm is universally optimal, that paradigm applicability is strongly shaped by query-corpus interactions, and that increased advanced mechanism does not necessarily yield better effectiveness-efficiency trade-offs. These findings underscore the necessity of routing-aware evaluation and establish a foundation for adaptive, interpretable, and generalizable next-generation RAG systems.

  • 6 authors
·
Jan 30

Unifying Molecular and Textual Representations via Multi-task Language Modelling

The recent advances in neural language models have also been successfully applied to the field of chemistry, offering generative solutions for classical problems in molecular design and synthesis planning. These new methods have the potential to optimize laboratory operations and fuel a new era of data-driven automation in scientific discovery. However, specialized models are still typically required for each task, leading to the need for problem-specific fine-tuning and neglecting task interrelations. The main obstacle in this field is the lack of a unified representation between natural language and chemical representations, complicating and limiting human-machine interaction. Here, we propose a multi-domain, multi-task language model to solve a wide range of tasks in both the chemical and natural language domains. By leveraging multi-task learning, our model can handle chemical and natural language concurrently, without requiring expensive pre-training on single domains or task-specific models. Interestingly, sharing weights across domains remarkably improves our model when benchmarked against state-of-the-art baselines on single-domain and cross-domain tasks. In particular, sharing information across domains and tasks gives rise to large improvements in cross-domain tasks, the magnitude of which increase with scale, as measured by more than a dozen of relevant metrics. Our work suggests that such models can robustly and efficiently accelerate discovery in physical sciences by superseding problem-specific fine-tuning and enhancing human-model interactions.

  • 6 authors
·
Jan 29, 2023

Diverse Beam Search: Decoding Diverse Solutions from Neural Sequence Models

Neural sequence models are widely used to model time-series data. Equally ubiquitous is the usage of beam search (BS) as an approximate inference algorithm to decode output sequences from these models. BS explores the search space in a greedy left-right fashion retaining only the top-B candidates - resulting in sequences that differ only slightly from each other. Producing lists of nearly identical sequences is not only computationally wasteful but also typically fails to capture the inherent ambiguity of complex AI tasks. To overcome this problem, we propose Diverse Beam Search (DBS), an alternative to BS that decodes a list of diverse outputs by optimizing for a diversity-augmented objective. We observe that our method finds better top-1 solutions by controlling for the exploration and exploitation of the search space - implying that DBS is a better search algorithm. Moreover, these gains are achieved with minimal computational or memory over- head as compared to beam search. To demonstrate the broad applicability of our method, we present results on image captioning, machine translation and visual question generation using both standard quantitative metrics and qualitative human studies. Further, we study the role of diversity for image-grounded language generation tasks as the complexity of the image changes. We observe that our method consistently outperforms BS and previously proposed techniques for diverse decoding from neural sequence models.

  • 7 authors
·
Oct 7, 2016

Reward-free Alignment for Conflicting Objectives

Direct alignment methods are increasingly used to align large language models (LLMs) with human preferences. However, many real-world alignment problems involve multiple conflicting objectives, where naive aggregation of preferences can lead to unstable training and poor trade-offs. In particular, weighted loss methods may fail to identify update directions that simultaneously improve all objectives, and existing multi-objective approaches often rely on explicit reward models, introducing additional complexity and distorting user-specified preferences. The contributions of this paper are two-fold. First, we propose a Reward-free Alignment framework for Conflicted Objectives (RACO) that directly leverages pairwise preference data and resolves gradient conflicts via a novel clipped variant of conflict-averse gradient descent. We provide convergence guarantees to Pareto-critical points that respect user-specified objective weights, and further show that clipping can strictly improve convergence rate in the two-objective setting. Second, we improve our method using some heuristics and conduct experiments to demonstrate the compatibility of the proposed framework for LLM alignment. Both qualitative and quantitative evaluations on multi-objective summarization and safety alignment tasks across multiple LLM families (Qwen 3, Llama 3, Gemma 3) show that our method consistently achieves better Pareto trade-offs compared to existing multi-objective alignment baselines.

  • 4 authors
·
Feb 2 3

PlantMarkerBench: A Multi-Species Benchmark for Evidence-Grounded Plant Marker Reasoning

Cell-type-specific marker genes are fundamental to plant biology, yet existing resources primarily rely on curated databases or high-throughput studies without explicitly modeling the supporting evidence found in scientific literature. We introduce PlantMarkerBench, a multi-species benchmark for evaluating literature-grounded plant marker evidence interpretation from full-text biological papers. PlantMarkerBench is constructed using a modular curation pipeline integrating large-scale literature retrieval, hybrid search, species-aware biological grounding, structured evidence extraction, and targeted human review. The benchmark spans four plant species -- Arabidopsis, maize, rice, and tomato -- and contains 5,550 sentence-level evidence instances annotated for marker-evidence validity, evidence type, and support strength. We define two benchmark tasks: determining whether a candidate sentence provides valid marker evidence for a gene-cell-type pair, and classifying the evidence into expression, localization, function, indirect, or negative categories. We benchmark diverse open-weight and closed-source language models across species and prompting strategies. Although frontier models achieve relatively strong performance on direct expression evidence, performance drops substantially on functional, indirect, and weak-support evidence, with evidence-type confusion emerging as a dominant failure mode. Open-weight models additionally exhibit elevated false-positive rates under ambiguous biological contexts. PlantMarkerBench provides a challenging and reproducible evaluation framework for literature-grounded biological evidence attribution and supports future research on trustworthy scientific information extraction and AI-assisted plant biology.

Vega-MT: The JD Explore Academy Translation System for WMT22

We describe the JD Explore Academy's submission of the WMT 2022 shared general translation task. We participated in all high-resource tracks and one medium-resource track, including Chinese-English, German-English, Czech-English, Russian-English, and Japanese-English. We push the limit of our previous work -- bidirectional training for translation by scaling up two main factors, i.e. language pairs and model sizes, namely the Vega-MT system. As for language pairs, we scale the "bidirectional" up to the "multidirectional" settings, covering all participating languages, to exploit the common knowledge across languages, and transfer them to the downstream bilingual tasks. As for model sizes, we scale the Transformer-Big up to the extremely large model that owns nearly 4.7 Billion parameters, to fully enhance the model capacity for our Vega-MT. Also, we adopt the data augmentation strategies, e.g. cycle translation for monolingual data, and bidirectional self-training for bilingual and monolingual data, to comprehensively exploit the bilingual and monolingual data. To adapt our Vega-MT to the general domain test set, generalization tuning is designed. Based on the official automatic scores of constrained systems, in terms of the sacreBLEU shown in Figure-1, we got the 1st place on {Zh-En (33.5), En-Zh (49.7), De-En (33.7), En-De (37.8), Cs-En (54.9), En-Cs (41.4) and En-Ru (32.7)}, 2nd place on {Ru-En (45.1) and Ja-En (25.6)}, and 3rd place on {En-Ja(41.5)}, respectively; W.R.T the COMET, we got the 1st place on {Zh-En (45.1), En-Zh (61.7), De-En (58.0), En-De (63.2), Cs-En (74.7), Ru-En (64.9), En-Ru (69.6) and En-Ja (65.1)}, 2nd place on {En-Cs (95.3) and Ja-En (40.6)}, respectively.

  • 12 authors
·
Sep 19, 2022

Towards Diverse Scientific Hypothesis Search with Large Language Models

Large language models (LLMs) are on the rise for accelerating scientific discovery, most recently in advanced tasks such as generating valid scientific hypotheses. Yet in many discovery settings, the goal is not to identify a single best hypothesis since validation can be noisy and expensive, and scientists benefit from a set of high-quality alternative hypotheses that hedge against downstream uncertainty for the best solutions. Nevertheless, commonly used evolutionary search recipes tend to prioritize optimization over exploration in hypothesis generation, and the resulting selection pressure during the search process leads to diversity collapse. Motivated by these limitations, we formulate hypothesis search as a sampling problem, where the objective is to efficiently produce diverse, high-quality hypotheses under a fixed validation budget. Building on this perspective, we propose \ours, an evolutionary framework inspired by the classical parallel tempering algorithm that searches hypotheses at multiple temperature levels and enables principled information exchange across temperatures to improve exploration without disrupting convergence. Across domains including molecular discovery, equation discovery, and algorithm discovery, our approach consistently improves both hypothesis quality and diversity under the same validation budget, and produces candidates that remain robust under more expensive downstream computational validations.

  • 10 authors
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Jun 9 2