The Clinical Genome Resource – Advancing genomic medicine through biocuration and expert assessment of genes and variants at scale

Project Summary/Abstract
High-quality evidence about clinically relevant genes and variants is a fundamental cornerstone of genomic
medicine. All aspects of clinical care derive from accurate information about the etiology, natural history, and
management of disease. With genomic analysis becoming more routine for patient care, the public availability
of well-curated and expertly adjudicated knowledge about genes and variants is critical. The ClinGen Resource
represents a highly collaborative effort of the genetics community to establish an evidence-based resource for
the assessment of the clinical relevance of genes and variants that is readily accessible to (and trusted by)
diagnostic laboratories, providers, and patients. Our objective is to improve patient care through enhanced and
accelerated curation of the clinical genome using innovative approaches to overcome challenges and address
new topics. We will accomplish this objective through the concerted pursuit of the following aims: aggregation
of structured evidence regarding genetic conditions and the genes and variants that cause them; application of
frameworks for expert curation of clinical validity, variant pathogenicity, and clinical actionability of genetic
conditions; broad dissemination of tools, standards, knowledge bases, and assertions about clinically relevant
genes and variants; and evaluation of all aspects of this work, so that we can improve the quality and impact of
the resource for implementation of transparent, reproducible, and evidence-based genomic medicine. The
proposal is innovative in several ways. It will aggregate data produced by cutting edge technologies, adapt
annotation tools to enable crowdsourcing through community curation, and apply advanced natural language
processing for annotation so that human curators can function at the top of their skill level. It will leverage the
participation of a large and enthusiastic community of volunteers, thus acting as a force multiplier for the NIH
funded teams. It will engage advocates who can conduct outreach within their areas of specialty, to further
extend the reach of ClinGen products into genomic medicine research and clinical care. It will transform a wide
range of clinical and basic science data into well-structured, transparently referenced expert assertions with
documentation of provenance and attention to ensuring the interoperability of the resource with diverse end-
users, including electronic health records. The proposed resource project is significant because in its entirety it
will improve, scale, and disseminate the freely available expert curation and interpretation of the human
genome to the global genomics community with the goal of improving health care for all people.

Grant Number: 5U24HG009650-09
NIH Institute/Center: NIH
Principal Investigator: JONATHAN BERG