Poster AGBT 2025

A high-plexity exome solution tailored for sensitive variant detection in single cells

Victor J. Weigman, Durga M. Arvapalli, Laurel Coons, Tia A. Tate, Tatiana V. Morozova, Jesse Ramirez, Subidhya Shrestha, Jon S. Zawistowski

BioSkryb Genomics, Durham, NC, USA

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The ability to obtain transcriptomic, genomic, and other omic insights at the resolution level of individual cells has revolutionized biological discovery. This exposure of ever-increasing degrees of heterogeneity, masked when performing bulk sequencing, has provided new understanding of gene expression subpopulations within a sample, aided reconstruction of clonal evolution, and guided mechanistic hypotheses for drug-resistant cells. Despite this, adoption of single-cell genomic sequencing has lagged behind single-cell transcriptional analysis, largely because of the expense of whole genome sequencing (WGS) that increases with the number of single cells sequenced. In addition, for researchers studying cancer and other diseases, sequence variation found in noncoding and regulatory genomic regions may be of less immediate interest compared to more interpretable or actionable variation found within coding sequences.

To address these needs, we present a workflow that couples BioSkryb’s ResolveDNA®1 Whole Genome Single-Cell Core Kit and ResolveOME™2 Whole Genome and Transcriptome Single-Cell Core Kit to third-party hybridization capture procedures for downstream whole exome sequencing (WES) of single cells. Highlights of the BioSkryb single-cell exome enrichment workflow include:

  • Optimized to existing Resolve core chemistries upstream of enrichment
  • Near-complete and uniform single-cell whole genome amplification creates high-quality genomic material for hybrid capture, ensuring optimal target capture (<2.5% of targets with 0 coverage) and reliable variant calling (average sensitivity >90%, average positive predictive value >98%).
  • 96 single-cell libraries in one enrichment reaction streamline the workflow and save on enrichment reagent cost.
  • An alternative to single-cell WGS that offers the ability to “right-size” an experiment to the biological goal with WES.