A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2020
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| _version_ | 1797091783819132928 |
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| author | KaramiNejadRanjbar, M Sharifzadeh, S Wietek, NC Artibani, M El-Sahhar, S Sauka-Spengler, T Yau, C Tresp, V Ahmed, AA |
| author_facet | KaramiNejadRanjbar, M Sharifzadeh, S Wietek, NC Artibani, M El-Sahhar, S Sauka-Spengler, T Yau, C Tresp, V Ahmed, AA |
| author_sort | KaramiNejadRanjbar, M |
| collection | OXFORD |
| description | 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 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 whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates all false positive 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.
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| first_indexed | 2024-03-07T03:37:27Z |
| format | Journal article |
| id | oxford-uuid:bcc4a602-f91c-4e0e-b39f-99f0a9a60244 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:37:27Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:bcc4a602-f91c-4e0e-b39f-99f0a9a602442022-03-27T05:26:51ZA highly accurate platform for clone-specific mutation discovery enables the study of active mutational processesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bcc4a602-f91c-4e0e-b39f-99f0a9a60244EnglishSymplectic ElementseLife Sciences Publications2020KaramiNejadRanjbar, MSharifzadeh, SWietek, NCArtibani, MEl-Sahhar, SSauka-Spengler, TYau, CTresp, VAhmed, AABulk 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 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 whole genome sequencing and analysis pipeline (DigiPico/MutLX) that virtually eliminates all false positive 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. |
| spellingShingle | KaramiNejadRanjbar, M Sharifzadeh, S Wietek, NC Artibani, M El-Sahhar, S Sauka-Spengler, T Yau, C Tresp, V Ahmed, AA A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title | A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title_full | A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title_fullStr | A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title_full_unstemmed | A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title_short | A highly accurate platform for clone-specific mutation discovery enables the study of active mutational processes |
| title_sort | highly accurate platform for clone specific mutation discovery enables the study of active mutational processes |
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