Molecular Phenotypes of Null Alleles in Cells (MorPhiC)

Phase 1

MorPhiC aims to develop a consistent catalog of molecular and cellular phenotypes for null alleles for every human gene by using in-vitro multicellular systems.

The 2020 NHGRI Strategic Vision laid out a set of “bold predictions for human genomics by 2030” that included: “The biological function(s) of every human gene will be known; for non-coding elements in the human genome, such knowledge will be the rule, rather than the exception.” Systematically obtaining genome-wide information about gene functions is critical for elucidating the roles and relationships of genes and regulatory elements in pathways and networks, which is one of the compelling genomic research projects outlined in the NHGRI Strategic Vision.

Program Goals

Conceived as one way to address this element of the Strategic Vision, MorPhiC aims to develop a consistent catalog of molecular and cellular phenotypes for null alleles for every human gene by using in-vitro multicellular systems. The catalog will be made available for broad use by the biomedical community. The program will start with a Phase 1 to optimize available methods to create null alleles and measure their phenotypic effects in a target subset of 1,000 protein coding genes across the program. Phase 1 will also assess the scale limitations of such methods, develop common data formats and establish use cases for this catalog.

Systematically obtaining information about the molecular and cellular phenotypic effects of gene knockouts for all human genes would provide wide-ranging insights into their biological function. Such data would provide a foothold for understanding the mechanisms through which genes act to produce phenotypes and would help elucidate the roles and relationships of genes and regulatory elements in pathways and networks.

MorPhiC Phase 1 will include three components:

Data Production Research and Development Centers will develop diverse systems and assays and explore and compare approaches to produce MorPhiC data at scale, and to maximize its informativeness.
Data Analysis and Validation Centers will undertake applicant-proposed analyses of the data in order to characterize its quality and utility for multiple purposes.
There will be a Data Resource and Administrative Coordinating Center.

All components will work together to ensure that the data are informative, of high quality and useful to the community.

See the MorPhiC Concept Document and Concept Clearance.

News

NIH initiative to systematically investigate and establish function of every human gene
September 27, 2022

Events

MorPhiC Data Analysis Validation Centers Pre-Application Webinar
September 7, 2022

MorPhiC Pre-Application Webinar
September 10, 2021

MorPhiC FOAs Frequently Asked Questions

Funding and Grants

Active

At this time, there are no current funding opportunities.

Expired

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase I: Data Analysis and Validation Centers (U01 Clinical trials not allowed)
RFA-HG-22-019
Expiration Date: November 2, 2022

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Production Research and Development Centers (UM1 clinical trials not allowed)
RFA-HG-21-029
Expiration Date: November 2, 2021

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Analysis and Validation Centers (U01 clinical trials not allowed)
RFA-HG-21-030
Expiration Date: November 2, 2021

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Resource and Administrative Coordinating Center (U24 clinical trials not allowed)
RFA-HG-21-031
Expiration Date: November 2, 2021

Grantee Information

Component	Principal Investigator	Institution	Title	Role/Mechanism
Data Production Research and Development Centers (DPCs)	Paul Robson	Jackson Laboratory	JAX MorPhiC Data Production Center	UM1 HG012651
	Danwei Huangfu	Sloan Kettering Institute	Center for scalable knockout and multimodal phenotyping in genetically diverse human genomes	UM1 HG012654
	Mazhar Adli	Northwestern University	Molecular and cellular characterization of essential human genes	UM1 HG012649
	Luke Gilbert	University of California, San Francisco	Spatial multiomic mapping of gene function with CRISPRoff	UM1 HG012660
Data Resource and Administrative Coordinating Center (DRACC)	Stephan Schurer	University of Miami School of Medicine	MorPhiC Data Resource and Administrative Coordinating Center	U24 HG012674
Data Analysis and Validation Centers (DAVs)	Jesse Engreitz	Stanford University	MorPhiC: Constructing a Catalog of Cellular Programs to Identify and Annotate Human Disease Genes	U01 HG013176
	Sheng Li	Jackson Laboratory	Multi-omic phenotyping of human transcriptional regulators	U01 HG013175
	Wei Sun	Fred Hutchinson Cancer Center	Statistical Methods for Inferring Gene-Phenotype Associations Using Omic Data from Gene Knockout and Human Phenotype Studies	U01 HG013177