Single-Cell Multi-Omic Correlation of Single Nucleotide Variants, Copy Number Variation, and Surface Epitopes for Clonal Profiling of Myeloma

Using cryopreserved, human multiple myeloma (MM) patient samples processed on the Mission Bio Tapestri single-cell platform, subclones were simultaneously analyzed for single nucleotide variants (SNV), copy number variants (CNV), clonotypes, and surface protein expression. We show here complex clonal evolution of MM in two patient samples as copy gains and losses were sequentially acquired and correlated with expression changes of MM heme/therapeutic markers. This high-resolution, single cell assay offers a potential new modality for the diagnosis and surveillance of patients with suspected MGUS, SGUS or high-risk MM. We have demonstrated exceptional results from cryopreserved human specimens, as well as the ability to use genetic lesion profiling to positively identify subclonal MM and correlate cell surface protein expression of potential therapeutic targets with each clonal population.