Large language models (LLMs) have become important tools in solving biological problems, offering improvements in accuracy and adaptability over conventional methods. Several benchmarks have been proposed to evaluate the performance of these LLMs. However, current benchmarks can hardly evaluate the performance of these models across diverse tasks effectively. In this paper, we introduce a comprehensive prompting-based benchmarking framework, termed Bio-benchmark, which includes 30 key bioinformatics tasks covering areas such as proteins, RNA, drugs, electronic health records, and traditional Chinese medicine. Using this benchmark, we evaluate six mainstream LLMs, including GPT-4o and Llama-3.1-70b, etc., using 0-shot and few-shot Chain-of-Thought (CoT) settings without fine-tuning to reveal their intrinsic capabilities. To improve the efficiency of our evaluations, we demonstrate BioFinder, a new tool for extracting answers from LLM responses, which increases extraction accuracy by round 30% compared to existing methods. Our benchmark results show the biological tasks suitable for current LLMs and identify specific areas requiring enhancement. Furthermore, we propose targeted prompt engineering strategies for optimizing LLM performance in these contexts. Based on these findings, we provide recommendations for the development of more robust LLMs tailored for various biological applications. This work offers a comprehensive evaluation framework and robust tools to support the application of LLMs in bioinformatics.

High-quality data resources play a crucial role in learning large language models (LLMs), particularly for low-resource languages like Cantonese. Despite having more than 85 million native speakers, Cantonese is still considered a low-resource language in the field of natural language processing (NLP) due to factors such as the dominance of Mandarin, lack of cohesion within the Cantonese-speaking community, diversity in character encoding and input methods, and the tendency of overseas Cantonese speakers to prefer using English. In addition, rich colloquial vocabulary of Cantonese, English loanwords, and code-switching characteristics add to the complexity of corpus collection and processing. To address these challenges, we collect Cantonese texts from a variety of sources, including open source corpora, Hong Kong-specific forums, Wikipedia, and Common Crawl data. We conduct rigorous data processing through language filtering, quality filtering, content filtering, and de-duplication steps, successfully constructing a high-quality Cantonese corpus of over 2 billion tokens for training large language models. We further refined the model through supervised fine-tuning (SFT) on curated Cantonese tasks, enhancing its ability to handle specific applications. Upon completion of the training, the model achieves state-of-the-art (SOTA) performance on four Cantonese benchmarks. After training on our dataset, the model also exhibits improved performance on other mainstream language tasks.

Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.