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.

LayerMatch: Do Pseudo-labels Benefit All Layers?

Deep neural networks have achieved remarkable performance across various tasks when supplied with large-scale labeled data. However, the collection of labeled data can be time-consuming and labor-intensive. Semi-supervised learning (SSL), particularly through pseudo-labeling algorithms that iteratively assign pseudo-labels for self-training, offers a promising solution to mitigate the dependency of labeled data. Previous research generally applies a uniform pseudo-labeling strategy across all model layers, assuming that pseudo-labels exert uniform influence throughout. Contrasting this, our theoretical analysis and empirical experiment demonstrate feature extraction layer and linear classification layer have distinct learning behaviors in response to pseudo-labels. Based on these insights, we develop two layer-specific pseudo-label strategies, termed Grad-ReLU and Avg-Clustering. Grad-ReLU mitigates the impact of noisy pseudo-labels by removing the gradient detrimental effects of pseudo-labels in the linear classification layer. Avg-Clustering accelerates the convergence of feature extraction layer towards stable clustering centers by integrating consistent outputs. Our approach, LayerMatch, which integrates these two strategies, can avoid the severe interference of noisy pseudo-labels in the linear classification layer while accelerating the clustering capability of the feature extraction layer. Through extensive experimentation, our approach consistently demonstrates exceptional performance on standard semi-supervised learning benchmarks, achieving a significant improvement of 10.38% over baseline method and a 2.44% increase compared to state-of-the-art methods.

BEACON: Benchmark for Comprehensive RNA Tasks and Language Models

RNA plays a pivotal role in translating genetic instructions into functional outcomes, underscoring its importance in biological processes and disease mechanisms. Despite the emergence of numerous deep learning approaches for RNA, particularly universal RNA language models, there remains a significant lack of standardized benchmarks to assess the effectiveness of these methods. In this study, we introduce the first comprehensive RNA benchmark BEACON (\textbf{BE}nchm\textbf{A}rk for \textbf{CO}mprehensive R\textbf{N}A Task and Language Models). First, BEACON comprises 13 distinct tasks derived from extensive previous work covering structural analysis, functional studies, and engineering applications, enabling a comprehensive assessment of the performance of methods on various RNA understanding tasks. Second, we examine a range of models, including traditional approaches like CNNs, as well as advanced RNA foundation models based on language models, offering valuable insights into the task-specific performances of these models. Third, we investigate the vital RNA language model components from the tokenizer and positional encoding aspects. Notably, our findings emphasize the superiority of single nucleotide tokenization and the effectiveness of Attention with Linear Biases (ALiBi) over traditional positional encoding methods. Based on these insights, a simple yet strong baseline called BEACON-B is proposed, which can achieve outstanding performance with limited data and computational resources. The datasets and source code of our benchmark are available at https://github.com/terry-r123/RNABenchmark.

Rethinking the BERT-like Pretraining for DNA Sequences

With the success of large-scale pretraining in NLP, there is an increasing trend of applying it to the domain of life sciences. In particular, pretraining methods based on DNA sequences have garnered growing attention due to their potential to capture generic information about genes. However, existing pretraining methods for DNA sequences largely rely on direct adoptions of BERT pretraining from NLP, lacking a comprehensive understanding and a specifically tailored approach. To address this research gap, we first conducted a series of exploratory experiments and gained several insightful observations: 1) In the fine-tuning phase of downstream tasks, when using K-mer overlapping tokenization instead of K-mer non-overlapping tokenization, both overlapping and non-overlapping pretraining weights show consistent performance improvement.2) During the pre-training process, using K-mer overlapping tokenization quickly produces clear K-mer embeddings and reduces the loss to a very low level, while using K-mer non-overlapping tokenization results in less distinct embeddings and continuously decreases the loss. 3) Using overlapping tokenization causes the self-attention in the intermediate layers of pre-trained models to tend to overly focus on certain tokens, reflecting that these layers are not adequately optimized. In summary, overlapping tokenization can benefit the fine-tuning of downstream tasks but leads to inadequate pretraining with fast convergence. To unleash the pretraining potential, we introduce a novel approach called RandomMask, which gradually increases the task difficulty of BERT-like pretraining by continuously expanding its mask boundary, forcing the model to learn more knowledge. RandomMask is simple but effective, achieving top-tier performance across 26 datasets of 28 datasets spanning 7 downstream tasks.