The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations

Abstract

The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings.

Insurance coverage does not predict outcomes of genetic testing: The search for meaning in payer decisions for germline cancer tests

“…Future assessments of patients having cancer genetic testing should include tracking patient outcomes following results disclosure to contribute clinical utility evidence. Of note, the current phase of the Clinical Sequencing Evidence‐Generating Research (CSER) consortium includes a clinical project providing hereditary cancer panel genetic testing and is focused in part on the clinical utility of genomic sequencing, and exploring medical follow up and cascade testing of relatives (Amendola et al, ).…”

Accurate, scalable cohort variant calls using DeepVariant and GLnexus

“…To maximize the diversity of samples and sites used for evaluation, other trios in the cohort were used to compute Mendelian violation rates (with the sole exception being the three person HG002-HG003-HG004 cohort) and the children of GIAB trios were excluded from the GIAB metrics calculations. The second data source is the Clinical Sequencing Evidence-Generating Research (CSER) consortium 26 , which contains 929 WGS and 344 WES samples, including 249 WGS trios and 112 WES trios. The third data source is the Population Architecture using Genomics and Epidemiology (PAGE) consortium 27 , which contains 313 WGS.…”

Towards a fine-scale population health monitoring system

“…With the advent of large, population-based DNA biobanks in health systems, new opportunities are available to characterize the links between demography and a broad range of health outcomes [3][4][5][6][7] . Knowledge about genetic variation shared across human populations can aid in understanding the demographic events that might impact disease burden across populations.…”