PROJECT SUMMARY Since the successful conclusion of the Human Genome Project (HGP), significant progress has been made towards the NHGRI strategic vision to characterize the biological function(s) of every human gene. A systematic catalogue of molecular and cellular phenotypic effects of gene knockouts for all human genes in complex cell- based model systems would fill a current gap between direct molecular readouts such as gene expression and whole model organism phenotypes. It would provide another critical tool to characterize the biological functions of all genes towards the strategic vision. The pilot phase of the Molecular and Cellular Phenotypes of Null Alleles in Cells (MorPhiC) program will study the feasibility, scalability, required scope, and utility of such a catalogue to characterize phenotypes associated with genes in tissue- and disease-relevant human cellular model systems. The proposed MorPhiC Data Resource and Administrative Coordinating Center (DRACC) will enable and support the MorPhiC research consortium by providing the highest quality FAIR (findable, accessible, interoperable, reusable) MorPhiC data resource, analyzing, annotating, and disseminating Morphic data, integrating external data/information, and serving as an administrative and coordination center. These functions will be fulfilled in close cooperation and collaborating with the Data Production Research and Development Centers (DPCs) and the Data Analysis and Validation Centers (DAVs) to support rigorous data standards, rich metadata annotations, the highest data and software quality, and reproducibility and portability of data processing and -analysis tools. Members of our team have previously served in leadership positions of several national and international research consortia, including the Human Cell Atlas (HCA), Knockout Mouse Program (KOMP), Genome-Wide Association Studies (GWAS) Catalog, Library of Integrated Network-based Cellular Signatures (LINCS), Illuminating the Druggable Genome (IDG), Big Data to Knowledge (BD2K), and Monarch Initiative. Our team has the technological, scientific, and administrative expertise to successfully operate the Center and complete the Center and Consortium critical functions and deliverables via Specific Aims to 1) Establish and operate the Center, 2) Deploy a state-of-the-art infrastructure to manage data across the entire life cycle, 3) Collate, converge, and deploy cloud-enabled analysis techniques, models and data processing protocols, 4) Create and deploy the MorPhiC Web Portal to provide global access to MorPhiC data, 5) Map and integrate external data sources, and 6) Administer and coordinate the Consortium. Successful completion of these Aims will enable the assessment of feasibility, scalability, required scope, and utility of a MorPhiC Catalogue with the prospect to massively scale the functional characterization of every human gene via phenotype mapping in relevant human model systems.

PROJECT NARRATIVE Despite huge progress in understanding the biological function of every human gene, significant hurdles remain, among them to establish a systematic catalogue of cellular phenotypes associated with each gene. The pilot phase of the Molecular and Cellular Phenotypes of Null Alleles in Cells (MorPhiC) program will study the feasibility, scalability, required scope, and utility of such a catalogue. Our proposed Data Resource and Administrative Coordinating Center (DRACC) will develop and deploy infrastructure and tools to provide the highest quality MorPhiC data resource, analyze, annotate, and disseminate MorPhiC data, integrating external data & information, and serve as an administrative and coordination center.