MorPhiC Consortium: towards functional characterization of all human genes

• 成果类型: Review
• 署名作者: Adli, Mazhar; Przybyla, Laralynne; Burdett, Tony; Burridge, Paul W.; Cacheiro, Pilar; Chang, Howard Y.; Engreitz, Jesse M.; Gilbert, Luke A.; Greenleaf, William J.; Hsu, Li; Huangfu, Danwei; Hung, Ling-Hong; Kundaje, Anshul; Li, Sheng; Parkinson, Helen; Qiu, Xiaojie; Robson, Paul; Schuerer, Stephan C.; Shojaie, Ali; Skarnes, William C.; Smedley, Damian; Studer, Lorenz; Sun, Wei; Vidovic, Dusica; Vierbuchen, Thomas; White, Brian S.; Yeung, Ka Yee; Yue, Feng; Zhou, Ting; MorPhiC Consortium, Neda
• 署名单位: Ann & Robert H. Lurie Children's Hospital of Chicago; Robert H. Lurie Comprehensive Cancer Center; Northwestern University; Feinberg School of Medicine; University of California System; University of California San Francisco; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Northwestern University; Feinberg School of Medicine; University of London; Queen Mary University London; Stanford University; Stanford University; Stanford University; University of California System; University of California San Francisco; Fred Hutchinson Cancer Center; Memorial Sloan Kettering Cancer Center; University of Washington; University of Washington Tacoma; Stanford University; Jackson Laboratory; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Miami; University of Washington; University of Washington Seattle; Ann & Robert H. Lurie Children's Hospital of Chicago; Robert H. Lurie Comprehensive Cancer Center; Northwestern University; Feinberg School of Medicine
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1709
• DOI: 10.1038/s41586-024-08243-w
• 发表日期: 2025-02-13
• 页码: 351-359
• 关键词: embryonic stem-cells; genome-wide; DISCOVERY; differentiation; knockouts; variants; sequence; MODEL

摘要

Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes. The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium aims to address this gap by creating a comprehensive catalogue of the molecular and cellular phenotypes associated with null alleles of all human genes using in vitro multicellular systems. In this Perspective, we present the strategic vision of the MorPhiC Consortium and discuss various strategies for generating null alleles, as well as the challenges involved. We describe the cellular models and scalable phenotypic readouts that will be used in the consortium's initial phase, focusing on 1,000 protein-coding genes. The resulting molecular and cellular data will be compiled into a catalogue of null-allele phenotypes. The methodologies developed in this phase will establish best practices for extending these approaches to all human protein-coding genes. The resources generated-including engineered cell lines, plasmids, phenotypic data, genomic information and computational tools-will be made available to the broader research community to facilitate deeper insights into human gene functions.