Consortium creates a robust, open-access platform to define the clinical relevance of genes and variants microbiologystudy

The Clinical Genome Resource (ClinGen), a resource that works to define the clinical relevance of genes and variants, has published data on more than 2,700 genes curated for relevance to genetic diseases, including cancer, cardiovascular disease and neurodevelopmental disorders.

A new publication in the journal Genetics in Medicine describes the methods of genomic curation and the development of software and infrastructure needed to support the ClinGen global consortium capable of large-scale evidence-based curation.

The ClinGen consortium, first established in 2013 by the National Human Genome Research Institute, now consists of more than 2,500 expert members representing 69 countries and territories. These experts form more than 100 disease-specific panels that work to identify which genes are validly implicated in disease, which variants in those genes are disease-causing and when medical actions are indicated. The goal of the consortium is to standardize assessment and curation of genomic information for use in medical practice and research.

The results of these efforts are available to the public on the Clinical Genome Resources website; all curated variants are also shared in the ClinVar database and ClinGen Evidence Repository, and all curated genes are shared with the GenCC database. As described in the paper, as of January 2024, ClinGen experts have identified and validated 2,420 gene-disease relationships, 1,557 genes for dosage sensitivity and actionability assessments for 447 gene-condition pairs across the pediatric and adult settings. Additionally, researchers have classified 5,161 unique pathogenic variants, and these numbers continue to grow.

“The ClinGen resource creates a robust, open-access platform to support genomic interpretation in clinics and research labs around the world,” said corresponding author Dr. Sharon Plon, co-principal investigator of the Baylor ClinGen project and professor of molecular and human genetics and pediatrics—hematology and oncology at Baylor. “The genomic knowledge produced by our consortium can be used to build evidence-based genetic testing panels, resolve discrepancies in variant classification and guide disclosure of genomic findings to patients.”

The work at Baylor focuses on developing software infrastructure and computational approaches to enable researchers to scale up the current work, expand the number of genes in the resource and facilitate integration into health care delivery. Baylor also leads research on hereditary cancer disease genes.

“The software engineering team at the Baylor Bioinformatics Research Laboratory developed key computational infrastructure for the project, including the Clingen Allele Registry, Criteria Specification Registry, and the Linked Data Hub. These application programming interface-centric microservices break new ground in academic software development and make ClinGen knowledge findable, accessible, interoperable and reusable,” said Dr. Aleksandar Milosavljevic, co-principal investigator of the Baylor ClinGen project, Bioinformatics Research Laboratory director and Henry and Emma Meyer Professor of Molecular Genetics at Baylor.