Ultrasensitive Quantitation of Genomic Chimerism by Single-Molecule Molecular Inversion Probe Capture and High-Throughput Sequencing of Copy Number Deletion Polymorphisms.

ABSTRACT: Genomic chimerism represents co-existing cells with different genotypes and has diagnostic significance in transplant engraftment monitoring, residual cancer detection, and other contexts. We previously described an approach to chimerism detection by interrogating variably present or absent genomic loci using single-molecule molecular inversion probes (smMIPs) and next-generation sequencing, which provided ultrasensitive limits of detection (<1 in 10,000 cells) but was not reliably quantitative. Herein, smMIP testing was modified to accurately quantitate chimeric cells by incorporating copy number neutral control loci for data normalization and computationally modeling cell mixtures from individual-specific genotypes. Data demonstrate precision and accuracy over three orders of magnitude (

SUBMITTER: Wu D 

PROVIDER: S-EPMC8819186 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature