Abstract
Bulk whole genome sequencing (WGS) enables the analysis of tumor evolution but, because of depth limitations, can only identify old mutational events. The discovery of current mutational processes for predicting the tumor's evolutionary trajectory requires dense sequencing of individual clones or single cells. Such studies, however, are inherently problematic because of the discovery of excessive false positive (FP) mutations when sequencing picogram quantities of DNA. Data pooling to increase the confidence in the discovered mutations, moves the discovery back in the past to a common ancestor. Here we report a robust WGS and analysis pipeline (DigiPico/MutLX) that virtually eliminates all F results while retaining an excellent proportion of true positives. Using our method, we identified, for the first time, a hyper-mutation (kataegis) event in a group of -30 cancer cells from a recurrent ovarian carcinoma. This was unidentifiable from the bulk WGS data. Overall, we propose DigiPico/MutLX method as a powerful framework for the identification of clone-specific variants at an unprecedented accuracy.
Item Type: | Journal article |
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Faculties: | Mathematics, Computer Science and Statistics > Computer Science |
Subjects: | 000 Computer science, information and general works > 004 Data processing computer science |
URN: | urn:nbn:de:bvb:19-epub-89018-3 |
ISSN: | 2050-084X |
Language: | English |
Item ID: | 89018 |
Date Deposited: | 25. Jan 2022, 09:28 |
Last Modified: | 27. Jan 2023, 07:29 |