Predicting phenotypes with complex genetic bases based on a small, interpretable set of variant features remains a challenging task. Conventionally, data-driven approaches are used for this task, yet the high dimensional nature of genotype data makes the analysis and prediction difficult. Motivated by the biomedical knowledge encoded in pre-trained LLMs and the emerging applications for genetics, we set to examine the ability of LLMs in feature selection and engineering for tabular genotype data, with a novel knowledge-driven framework. We develop FREEFORM, Free-flow Reasoning and Ensembling for Enhanced Feature Output and Robust Modeling, designed with chain-of-thought and ensembling principles, to select and engineer features with the intrinsic knowledge of LLMs. Evaluated on two distinct genotype-phenotype datasets, genetic ancestry and hereditary hearing loss, we find this framework outperforms several data-driven methods, particularly on low-data regimes. FREEFORM is available as open-source framework at GitHub: https://github.com/PennShenLab/FREEFORM.

Due to the hierarchical organization of RNA structures and their pivotal roles in fulfilling RNA functions, the formation of RNA secondary structure critically influences many biological processes and has thus been a crucial research topic. This review sets out to explore the computational prediction of RNA secondary structure and its connections to RNA modifications, which have emerged as an active domain in recent years. We first examine the progression of RNA secondary structure prediction methodology, focusing on a set of representative works categorized into thermodynamic, comparative, machine learning, and hybrid approaches. Next, we survey the advances in RNA modifications and computational methods for identifying RNA modifications, focusing on the prominent modification types. Subsequently, we highlight the interplay between RNA modifications and secondary structures, emphasizing how modifications such as m6A dynamically affect RNA folding and vice versa. In addition, we also review relevant data sources and provide a discussion of current challenges and opportunities in the field. Ultimately, we hope our review will be able to serve as a cornerstone to aid in the development of innovative methods for this emerging topic and foster therapeutic applications in the future.

Recent advancements in large language models (LLMs) have achieved promising performances across various applications. Nonetheless, the ongoing challenge of integrating long-tail knowledge continues to impede the seamless adoption of LLMs in specialized domains. In this work, we introduce DALK, a.k.a. Dynamic Co-Augmentation of LLMs and KG, to address this limitation and demonstrate its ability on studying Alzheimer’s Disease (AD), a specialized sub-field in biomedicine and a global health priority. With a synergized framework of LLM and KG mutually enhancing each other, we first leverage LLM to construct an evolving AD-specific knowledge graph (KG) sourced from AD-related scientific literature, and then we utilize a coarse-to-fine sampling method with a novel self-aware knowledge retrieval approach to select appropriate knowledge from the KG to augment LLM inference capabilities. The experimental results, conducted on our constructed AD question answering (ADQA) benchmark, underscore the efficacy of DALK. Additionally, we perform a series of detailed analyses that can offer valuable insights and guidelines for the emerging topic of mutually enhancing KG and LLM.