Engineered Variant Clones Confirmed for MDIC’s Somatic Reference Sample (SRS) Initiative

MDIC’s Somatic Reference Samples (SRS) Initiative has reached a significant milestone in its mission to enhance the accuracy and reproducibility of next-generation sequencing (NGS)-based cancer diagnostics. The SRS Bioinformatics Team has confirmed the successful engineering of clinically relevant cancer variants into the highly characterized NIST Genome In A Bottle (GIAB) cell line, HG002, a critical step toward developing standardized reference materials for the field.

The CRISPR-Cas9 engineered HG002 clones are designed to serve as a precursor to somatic reference sample mixtures, which will provide a replenishable and highly validated resource for laboratories and test developers. These mixtures will optimize NGS-based test validation by ensuring greater consistency, reliability, and clinical relevance in genomic testing.

Initial assessments of the engineered clones were presented at the Advances in Genome Biology and Technology (AGBT) 2025 General Meeting, underscoring the initiative’s potential to advance genomic standardization. The presented research poster is available for download below.

Intended genome edits were verified using whole genome sequencing (WGS) and analysis of RNA-seq data indicates fusion clone expression. These results informed clone selection for the SRS mixtures, which will include a range of variant types, including single and multi-nucleotide variants (SNVs and MNVs), INDELS, and gene fusions.

This work is a collaborative effort with the GIAB Team at the National Institute of Standards and Technology (NIST) and Revvity, Inc. and has been supported by funding from Illumina, Quidel, the National Philanthropic Trust, and the Gordon and Betty Moore Foundation.

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