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ICCG, Awaiting Funding, Moves Ahead with Plans to Build Database of Genomic, Phenotypic Information


Members of the International Collaboration for Clinical Genetics gathered earlier this month to discuss the aims of a proposed effort to develop a database of genomic variation.

While it moves ahead with its plans, the ICCG is still awaiting word on a grant application to the US National Institutes of Health, which it hopes will fund the project going forward.

Heidi Rehm, an ICCG steering commitee member, told BioArray News this week that the ICCG has applied for funds to cover about $5 million in direct costs associated with the project across three years. "And although the grant is a three-year grant, we anticipate applying for many renewals as this project is definitely one without an end date," said Rehm, who is director of the Laboratory for Molecular Medicine at Partners Healthcare Center for Personalized Genetic Medicine in Boston.

The ICCG was created last year as a partnership between the International Standards for Cytogenomics Array consortium and clinical laboratories that are using next-generation sequencing, as opposed to microarray technology, as their main platform for genetic testing, as well as clinical geneticists for whom technology platform is of lesser importance than understanding the significance of genomic variation (BAN 10/23/2012).

Since its inception, the ICCG's main thrust has been toward developing a "unified database with associated curation and evidence-based resources to set the standards for quality in clinical genomic testing," according to Christa Lese Martin, another steering committee member. By collecting "high-quality, curated genotype and phenotype information" in one database, the ICCG hopes that it can help geneticists to better understand the "biological and medical significance of genomic variation," said
Martin, who is a director and senior investigator at Geisinger Health System's Autism and Developmental Medicine Institute in Danville, Pa.

More specifically, the group aims to coordinate the submission of variant and phenotypic data into ClinVar, a universal centralized database hosted by the National Center for Biotechnology Information. Part of that effort was already underway at ISCA, where members created a copy number variation atlas of human development under a two-year, $3.5 million NIH grant that expired last summer. And since the formation of the ICCG, more than 10,000 variants have been submitted by various labs that use sequencing, Rehm said, including the LMM, Ambry Genetics, Emory Genetics Laboratory, and others.

The ICCG now hopes to use the new funding, should it be awarded, to further pursue those goals. It has formed five working groups focused on sequence variation; structural variation; phenotyping; engagement, education, and access; and bioinformatics and IT. According to the ICCG, the sequence variant working group's aims include developing standards for variant classification, guiding ClinVar development, defining the medical exome, and soliciting and supporting labs in their data submissions.

The structural variation working group is reviewing genes and regions on ISCA's consensus array design for constitutional genetic testing. It is also developing a genome-wide dosage sensitivity map to aid in clinical array interpretation and to inform future array designs. "Going forward, the efforts of this group will continue to add genes [and] regions to the reviewed list, which has also proven to be useful in clinical interpretation of array results, since evidence for haploinsufficiency, [or losses], and triplosensitivity, [or gains], are being evaluated for each locus," said Martin.

ICCG's phenotyping working group hopes to improve the collection of phenotypic data for association with genotypes, and "ensure the use of consistent and compatible terminologies and ontologies across interconnected phenotype resources," according to the organization.

Martin said that the ICCG has "significantly increased the activities related to collecting more rich phenotypic data" since its formation, adding that the group's goal is to "integrate genotype with phenotype for both clinical and research purposes."

ICCG's engagement, education, and access working group is charged with "educating stakeholders on ICCG efforts," encouraging data submission, and ensuring access to data and resources, according to the organization, while its bioinformatics and IT working group aims to guide communication between labs, vendors, and the NCBI, and to develop submission standards for ClinVar.

"It is always a challenge for busy clinical laboratories to take extra time to submit data," said Martin. "However, we are actively working with ClinVar to make data submission as easy as possible," she said. "As we learn more about the data submission and curation process, we are finding that contributing data to a centralized database improves data quality," Martin added. "The curation of data within and between laboratories allows any discrepancies in data interpretation to be identified and addressed."