Marc Feuermann - A draft functionome from evolutionary modeling and experimental GO annotations
Channel: Biocuration Conference 2023
Date: 2023-06-22

*Title:* A complete draft human gene functionome from large-scale evolutionary modeling and experimental Gene Ontology annotations

*Session:* April 26 - Community 1 - 01

*Abstract:* Understanding the human functionome – the set of functions performed by the protein-coding genes of the human genome – has been a longstanding goal of biomedical research. The last two decades has seen substantial progress towards achieving this goal, with continued improvements in the annotation of the human genome sequence, and dramatic advances in the experimental characterization of human genes and their homologs from well-studied model organisms. Here, we describe the first attempt to create a complete, draft human functionome through a comprehensive synthesis of functional data obtained for human genes and their homologs in non-human model organisms. All relevant function information in the Gene Ontology knowledgebase has been synthesized using an evolutionary framework based on phylogenetic trees, creating curated models of function evolution for thousands of gene families, which are updated as new knowledge accumulates. Our draft human functionome specifies at least one functional characteristic for 80% of human protein-coding genes, each of which can be individually traced to experimental evidence in human and/or non-human model systems. Our analyses of these models and annotations provide insights into the nature of function evolution and the importance of gene duplication in this process, as well as a quantitative estimate of the contribution of studies in model organisms to our current understanding of human gene function. We expect that the evolutionary models and resulting GO annotations will be useful in numerous applications from gene set enrichment analysis to understanding genetic evolution.