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<p>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.</p>

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MorPhiC Consortium: towards functional characterization of all human genes

  • 期刊论文

  • 发表日期：

    2025年2月12日

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  • Mazhar Adli,
  • Laralynne Przybyla,
  • Tony Burdett,
  • Paul W. Burridge,
  • Pilar Cacheiro,
  • Howard Y. Chang,
  • Jesse M. Engreitz,
  • Luke A. Gilbert,
  • William J. Greenleaf,
  • Li Hsu,
  • Danwei Huangfu,
  • Ling-Hong Hung,
  • Anshul Kundaje,
  • Sheng Li,
  • Helen Parkinson,
  • Xiaojie Qiu,
  • Paul Robson,
  • Stephan C. Schürer,
  • Ali Shojaie,
  • William C. Skarnes,
  • Damian Smedley,
  • Lorenz Studer,
  • Wei Sun,
  • Dušica Vidović,
  • Thomas Vierbuchen,
  • Brian S. White,
  • Ka Yee Yeung,
  • Feng Yue,
  • Ting Zhou,
  • Neda Abbaszadeh,
  • Juliana Alcoforado Diniz,
  • Anahita Amiri,
  • Rohan N. V. S. R. K. Avireddy,
  • Tao Bai,
  • Dylan S. Baker,
  • Jacob J. Baroch,
  • Chia Chan,
  • Sijie Chen,
  • Xintong Chen,
  • Hyein S. Cho,
  • Anshul Choudhary,
  • Caty E. Chung,
  • Thomas J. Dahlstrom,
  • Anthony Doty,
  • Basak Eraslan,
  • Adam L. Felsenfeld,
  • Patrick J. Fleming,
  • Colin F. Fletcher,
  • Jesse Flores,
  • William F. Flynn,
  • Yihao Fu,
  • Bryce Nobutoshi Fukuda,
  • Jessica L. Garofalo,
  • Rachel A. Glenn,
  • Juhee Goyal,
  • Alexandra M. Griffiths,
  • Tingfeng Guo,
  • Revant Gupta,
  • Dipayan Gupta,
  • Nan Hu,
  • Yung-Hsin Huang,
  • Aaron J. Huebner,
  • Carolyn Hutter,
  • Angelina Kendra,
  • Gina Kirsammer,
  • Orges A. Koci,
  • Katerina Kraft,
  • Zhaoheng Li,
  • Shuzhao Li,
  • Si Liu,
  • Zukai Liu,
  • Dingyu Liu,
  • Nianping Liu,
  • Renhe Luo,
  • Davi Lyra Leite,
  • Yuzhen Mao,
  • Gabriel Marengo,
  • Justin A. McDonough,
  • Adrian Melo-Carrillo,
  • Chen Meng,
  • Eyal Metzl-Raz,
  • Joshua M. Mitchell,
  • Varun Mittal,
  • Niharika Nasam,
  • Ozlem Neyisci,
  • Gang Ning,
  • Devon Parker,
  • Marcin Pilarczyk,
  • Ajay Pillai,
  • Olivier B. Poirion,
  • Praeploy Pongpamorn,
  • Arushi Rana,
  • Jamilex Rivera-Diaz,
  • Nicolette C. Ross,
  • Enrique Sapena Ventura,
  • Fidan Seker,
  • Kaustav Sengupta,
  • Anu Shivalikanjli,
  • Wenzhuo Tang,
  • Denis Torre,
  • Ping Wang,
  • Xianming Wang,
  • De Xing,
  • Dapeng Yang,
  • Galabina N. Yordanova,
  • Bo Yu,
  • Tony Zeng,
  • Stephen Zhang,
  • Zhehao Zhang,
  • Nan Zhang,
  • Hengqiang Zhao,
  • Shujian Zheng,
  • Aaron Zhong,
  • Justina Žurauskienė

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.