Somatic Reference Samples Initiative
Overview
The Somatic Reference Samples (SRS) Initiative seeks to create well-characterized reference samples to validate NGS-based cancer diagnostics. Funded by industry and philanthropic organizations, the pilot project aims to develop an initial set of 10 cell line-based reference samples with validated data sets. Key objectives include providing tools for NGS-based diagnostic test validation, establishing a sustainable model for reference sample generation, and expanding to other cancers and diseases. Key stakeholders include the FDA, NIH, NIST, CDC, diagnostics manufacturers, funding bodies, and payers.
The project is divided into three phases:
- Phase I (completed in October 2021) produced a landscape analysis of gene variants linked to human cancers and available reference materials.
- Phase II (May 2022–December 2025) focuses on gene editing, manufacturing, data analysis and integration, and commercialization.
- Phase III (in development) will define use cases, determine the next samples, and secure additional funding.
Deliverables include mixtures of variant-containing cell lines in FFPE format and validated data sets.
On Demand Webinar: The Somatic Reference Sample Initiative
In this webinar, a panel of experts discuss the Somatic Reference Samples (SRS) Initiative, a public-private partnership convened by MDIC that guides the development of reference samples used to develop and validate NGS-based cancer diagnostics.
Somatic Reference Standards Working Group
As the project moved from Phase 1 variant selection to Phase 2 development of reference samples in 2018, the project leadership structure was updated from Working Group to Steering Committee oversight.
Active SRS Steering Committee members represent the following IVD stakeholders:
- Illumina
- NIST
- Optum
- Precision Medicine & Diagnostics (PMDx)
- CDC
- FDA
- NIH
Want to Get Involved?
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SRS Landscape Analysis Report
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Advancing Precision in Variant Detection: Announcing the HG002 Somatic Benchmark
MDIC’s SRS Bioinformatics Team has created a somatic benchmark resource in collaboration with the Genome In A Bottle Team (GIAB) at the National Institute of Standards and Technology (NIST) and eight external validators. Using a trio-based approach, low frequency (i.e. mosaic) variants down to 5% VAF (variant allele frequency) were characterized in a reference human (HG002) cell line. A preprint and the HG002 mosaic benchmark are now publicly available. This preliminary work will help to further characterize the NIST GIAB HG002 cell line which was used to develop the Somatic Reference Sample (SRS) Initiative pilot material, and comparisons to HG002 clones edited with clinically relevant cancer variants across next generation sequencing platforms are scheduled for 2025.