RESUMEN
Identifying key genes from a list of differentially expressed genes (DEGs) is a critical step in transcriptome analysis. However, current methods, including Gene Ontology analysis and manual annotation, essentially rely on existing knowledge, which is highly biased depending on the extent of the literature. As a result, understudied genes, some of which may be associated with important molecular mechanisms, are often ignored or remain obscure. To address this problem, we propose Clover, a data-driven scoring method to specifically highlight understudied genes. Clover aims to prioritize genes associated with important molecular mechanisms by integrating three metrics: the likelihood of appearing in the DEG list, tissue specificity, and number of publications. We applied Clover to Alzheimer's disease data and confirmed that it successfully detected known associated genes. Moreover, Clover effectively prioritized understudied but potentially druggable genes. Overall, our method offers a novel approach to gene characterization and has the potential to expand our understanding of gene functions. Clover is an open-source software written in Python3 and available on GitHub at https://github.com/G708/Clover.
Asunto(s)
Enfermedad de Alzheimer , Perfilación de la Expresión Génica , Programas Informáticos , Humanos , Perfilación de la Expresión Génica/métodos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Transcriptoma/genética , Biología Computacional/métodos , Ontología de GenesRESUMEN
Cohesin regulates gene expression through context-specific chromatin folding mechanisms such as enhancer-promoter looping and topologically associating domain (TAD) formation by cooperating with factors such as cohesin loaders and the insulation factor CTCF. We developed a computational workflow to explore how three-dimensional (3D) structure and gene expression are regulated collectively or individually by cohesin and related factors. The main component is CustardPy, by which multi-omics datasets are compared systematically. To validate our methodology, we generated 3D genome, transcriptome, and epigenome data before and after depletion of cohesin and related factors and compared the effects of depletion. We observed diverse effects on the 3D genome and transcriptome, and gene expression changes were correlated with the splitting of TADs caused by cohesin loss. We also observed variations in long-range interactions across TADs, which correlated with their epigenomic states. These computational tools and datasets will be valuable for 3D genome and epigenome studies.