Biology Instructions: A Dataset and Benchmark for Multi-Omics Sequence Understanding Capability of Large Language Models

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

Model Decides How to Tokenize: Adaptive DNA Sequence Tokenization with MxDNA

Foundation models have made significant strides in understanding the genomic language of DNA sequences. However, previous models typically adopt the tokenization methods designed for natural language, which are unsuitable for DNA sequences due to their unique characteristics. In addition, the optimal approach to tokenize DNA remains largely under-explored, and may not be intuitively understood by humans even if discovered. To address these challenges, we introduce MxDNA, a novel framework where the model autonomously learns an effective DNA tokenization strategy through gradient decent. MxDNA employs a sparse Mixture of Convolution Experts coupled with a deformable convolution to model the tokenization process, with the discontinuous, overlapping, and ambiguous nature of meaningful genomic segments explicitly considered. On Nucleotide Transformer Benchmarks and Genomic Benchmarks, MxDNA demonstrates superior performance to existing methods with less pretraining data and time, highlighting its effectiveness. Finally, we show that MxDNA learns unique tokenization strategy distinct to those of previous methods and captures genomic functionalities at a token level during self-supervised pretraining. Our MxDNA aims to provide a new perspective on DNA tokenization, potentially offering broad applications in various domains and yielding profound insights.

COMET: Benchmark for Comprehensive Biological Multi-omics Evaluation Tasks and Language Models

As key elements within the central dogma, DNA, RNA, and proteins play crucial roles in maintaining life by guaranteeing accurate genetic expression and implementation. Although research on these molecules has profoundly impacted fields like medicine, agriculture, and industry, the diversity of machine learning approaches-from traditional statistical methods to deep learning models and large language models-poses challenges for researchers in choosing the most suitable models for specific tasks, especially for cross-omics and multi-omics tasks due to the lack of comprehensive benchmarks. To address this, we introduce the first comprehensive multi-omics benchmark COMET (Benchmark for Biological COmprehensive Multi-omics Evaluation Tasks and Language Models), designed to evaluate models across single-omics, cross-omics, and multi-omics tasks. First, we curate and develop a diverse collection of downstream tasks and datasets covering key structural and functional aspects in DNA, RNA, and proteins, including tasks that span multiple omics levels. Then, we evaluate existing foundational language models for DNA, RNA, and proteins, as well as the newly proposed multi-omics method, offering valuable insights into their performance in integrating and analyzing data from different biological modalities. This benchmark aims to define critical issues in multi-omics research and guide future directions, ultimately promoting advancements in understanding biological processes through integrated and different omics data analysis.

Two Heads Are Better Than One: A Multi-Agent System Has the Potential to Improve Scientific Idea Generation

The rapid advancement of scientific progress requires innovative tools that can accelerate discovery. While recent AI methods, particularly large language models (LLMs), have shown promise in tasks such as hypothesis generation and experimental design, they fall short in replicating the collaborative nature of real-world scientific practices, where diverse teams of experts work together to tackle complex problems. To address the limitation, we propose an LLM-based multi-agent system, i.e., Virtual Scientists (VirSci), designed to mimic the teamwork inherent in scientific research. VirSci organizes a team of agents to collaboratively generate, evaluate, and refine research ideas. Through comprehensive experiments, we demonstrate that this multi-agent approach outperforms the state-of-the-art method in producing novel and impactful scientific ideas, showing potential in aligning with key insights in the Science of Science field. Our findings suggest that integrating collaborative agents can lead to more innovative scientific outputs, offering a robust system for autonomous scientific discovery.

Benchmarking Fish Dataset and Evaluation Metric in Keypoint Detection -- Towards Precise Fish Morphological Assessment in Aquaculture Breeding

Accurate phenotypic analysis in aquaculture breeding necessitates the quantification of subtle morphological phenotypes. Existing datasets suffer from limitations such as small scale, limited species coverage, and inadequate annotation of keypoints for measuring refined and complex morphological phenotypes of fish body parts. To address this gap, we introduce FishPhenoKey, a comprehensive dataset comprising 23,331 high-resolution images spanning six fish species. Notably, FishPhenoKey includes 22 phenotype-oriented annotations, enabling the capture of intricate morphological phenotypes. Motivated by the nuanced evaluation of these subtle morphologies, we also propose a new evaluation metric, Percentage of Measured Phenotype (PMP). It is designed to assess the accuracy of individual keypoint positions and is highly sensitive to the phenotypes measured using the corresponding keypoints. To enhance keypoint detection accuracy, we further propose a novel loss, Anatomically-Calibrated Regularization (ACR), that can be integrated into keypoint detection models, leveraging biological insights to refine keypoint localization. Our contributions set a new benchmark in fish phenotype analysis, addressing the challenges of precise morphological quantification and opening new avenues for research in sustainable aquaculture and genetic studies. Our dataset and code are available at https://github.com/WeizhenLiuBioinform/Fish-Phenotype-Detect.

Revealing Hierarchical Structure of Leaf Venations in Plant Science via Label-Efficient Segmentation: Dataset and Method

Hierarchical leaf vein segmentation is a crucial but under-explored task in agricultural sciences, where analysis of the hierarchical structure of plant leaf venation can contribute to plant breeding. While current segmentation techniques rely on data-driven models, there is no publicly available dataset specifically designed for hierarchical leaf vein segmentation. To address this gap, we introduce the HierArchical Leaf Vein Segmentation (HALVS) dataset, the first public hierarchical leaf vein segmentation dataset. HALVS comprises 5,057 real-scanned high-resolution leaf images collected from three plant species: soybean, sweet cherry, and London planetree. It also includes human-annotated ground truth for three orders of leaf veins, with a total labeling effort of 83.8 person-days. Based on HALVS, we further develop a label-efficient learning paradigm that leverages partial label information, i.e. missing annotations for tertiary veins. Empirical studies are performed on HALVS, revealing new observations, challenges, and research directions on leaf vein segmentation.

An Embarrassingly Simple Approach to Enhance Transformer Performance in Genomic Selection for Crop Breeding

Genomic selection (GS), as a critical crop breeding strategy, plays a key role in enhancing food production and addressing the global hunger crisis. The predominant approaches in GS currently revolve around employing statistical methods for prediction. However, statistical methods often come with two main limitations: strong statistical priors and linear assumptions. A recent trend is to capture the non-linear relationships between markers by deep learning. However, as crop datasets are commonly long sequences with limited samples, the robustness of deep learning models, especially Transformers, remains a challenge. In this work, to unleash the unexplored potential of attention mechanism for the task of interest, we propose a simple yet effective Transformer-based framework that enables end-to-end training of the whole sequence. Via experiments on rice3k and wheat3k datasets, we show that, with simple tricks such as k-mer tokenization and random masking, Transformer can achieve overall superior performance against seminal methods on GS tasks of interest.

ContraNovo: A Contrastive Learning Approach to Enhance De Novo Peptide Sequencing

De novo peptide sequencing from mass spectrometry (MS) data is a critical task in proteomics research. Traditional de novo algorithms have encountered a bottleneck in accuracy due to the inherent complexity of proteomics data. While deep learning-based methods have shown progress, they reduce the problem to a translation task, potentially overlooking critical nuances between spectra and peptides. In our research, we present ContraNovo, a pioneering algorithm that leverages contrastive learning to extract the relationship between spectra and peptides and incorporates the mass information into peptide decoding, aiming to address these intricacies more efficiently. Through rigorous evaluations on two benchmark datasets, ContraNovo consistently outshines contemporary state-of-the-art solutions, underscoring its promising potential in enhancing de novo peptide sequencing. The source code is available at https://github.com/BEAM-Labs/ContraNovo.

zkFL: Zero-Knowledge Proof-based Gradient Aggregation for Federated Learning

Federated Learning (FL) is a machine learning paradigm, which enables multiple and decentralized clients to collaboratively train a model under the orchestration of a central aggregator. Traditional FL solutions rely on the trust assumption of the centralized aggregator, which forms cohorts of clients in a fair and honest manner. However, a malicious aggregator, in reality, could abandon and replace the client's training models, or launch Sybil attacks to insert fake clients. Such malicious behaviors give the aggregator more power to control clients in the FL setting and determine the final training results. In this work, we introduce zkFL, which leverages zero-knowledge proofs (ZKPs) to tackle the issue of a malicious aggregator during the training model aggregation process. To guarantee the correct aggregation results, the aggregator needs to provide a proof per round. The proof can demonstrate to the clients that the aggregator executes the intended behavior faithfully. To further reduce the verification cost of clients, we employ a blockchain to handle the proof in a zero-knowledge way, where miners (i.e., the nodes validating and maintaining the blockchain data) can verify the proof without knowing the clients' local and aggregated models. The theoretical analysis and empirical results show that zkFL can achieve better security and privacy than traditional FL, without modifying the underlying FL network structure or heavily compromising the training speed.

Defending Against Malicious Behaviors in Federated Learning with Blockchain

In the era of deep learning, federated learning (FL) presents a promising approach that allows multi-institutional data owners, or clients, to collaboratively train machine learning models without compromising data privacy. However, most existing FL approaches rely on a centralized server for global model aggregation, leading to a single point of failure. This makes the system vulnerable to malicious attacks when dealing with dishonest clients. In this work, we address this problem by proposing a secure and reliable FL system based on blockchain and distributed ledger technology. Our system incorporates a peer-to-peer voting mechanism and a reward-and-slash mechanism, which are powered by on-chain smart contracts, to detect and deter malicious behaviors. Both theoretical and empirical analyses are presented to demonstrate the effectiveness of the proposed approach, showing that our framework is robust against malicious client-side behaviors.