FERMI: A Novel Method for Sensitive Detection of Rare Mutations in Somatic Tissue
Year: 2019
Type: article
Abstract: With growing interest in monitoring mutational processes in normal tissues, tumor heterogeneity, and cancer evolution under therapy, the ability to accurately and economically detect ultra-rare mutations is becoming increasingly important. However, this capability has often been compromised by significant sequencing, PCR and DNA preparation error rates. Here, we describe FERMI (Fast Extremely Rare Mutation Identification) - a novel method designed to eliminate the majority of these sequencing and library-preparation errors in order to significantly improve rare somatic mutation detection. This method leverages barcoded targeting probes to capture and sequence DNA of interest with single copy resolution. The variant calls from the barcoded sequencing data are then further filtered in a position-dependent fashion against an adaptive, context-aware null model in order to distinguish true variants. As a proof of principle, we employ FERMI to probe bone marrow biopsies from leukemia patients, and show that rare mutations and clonal evolution can be tracked throughout cancer treatment, including during historically intractable periods like minimum residual disease. Importantly, FERMI is able to accurately detect nascent clonal expansions within leukemias in a manner that may facilitate the early detection and characterization of cancer relapse.
Source: G3 Genes Genomes Genetics
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,709
Funders: Leukemia and Lymphoma Society, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences, University of Colorado School of Medicine, Anschutz Medical Campus, Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Anschutz Medical Campus
Awards: G215709867, G2310783216, G3221852482, G402463744, The Role of Trisomy 21 in Hematopoiesis and Leukemogenesis, Computational approaches for identifying epigenomic contexts of somatic mutations, G783754770, G9000016995, G9000039344, G9000258341, Cancer Center Support Grant, University of Colorado Cancer Center Support Grant
OpenAlex ID: W2964948469