Distinguishing excess mutations and increased cell death based on variant allele frequencies.
Tumors often harbor orders of magnitude more mutations than healthy tissues. The increased number of mutations may be due to an elevated mutation rate or frequent cell death and correspondingly rapid cell turnover, or a combination of the two. It is difficult to disentangle these two mechanisms base...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010048 |
| _version_ | 1811292771562029056 |
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| author | Gergely Tibély Dominik Schrempf Imre Derényi Gergely J Szöllősi |
| author_facet | Gergely Tibély Dominik Schrempf Imre Derényi Gergely J Szöllősi |
| author_sort | Gergely Tibély |
| collection | DOAJ |
| description | Tumors often harbor orders of magnitude more mutations than healthy tissues. The increased number of mutations may be due to an elevated mutation rate or frequent cell death and correspondingly rapid cell turnover, or a combination of the two. It is difficult to disentangle these two mechanisms based on widely available bulk sequencing data, where sequences from individual cells are intermixed and, thus, the cell lineage tree of the tumor cannot be resolved. Here we present a method that can simultaneously estimate the cell turnover rate and the rate of mutations from bulk sequencing data. Our method works by simulating tumor growth and finding the parameters with which the observed data can be reproduced with maximum likelihood. Applying this method to a real tumor sample, we find that both the mutation rate and the frequency of death may be high. |
| first_indexed | 2024-04-13T04:50:25Z |
| format | Article |
| id | doaj.art-336401b7b3fd457abc75277995ed663c |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-13T04:50:25Z |
| publishDate | 2022-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-336401b7b3fd457abc75277995ed663c2022-12-22T03:01:41ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-04-01184e101004810.1371/journal.pcbi.1010048Distinguishing excess mutations and increased cell death based on variant allele frequencies.Gergely TibélyDominik SchrempfImre DerényiGergely J SzöllősiTumors often harbor orders of magnitude more mutations than healthy tissues. The increased number of mutations may be due to an elevated mutation rate or frequent cell death and correspondingly rapid cell turnover, or a combination of the two. It is difficult to disentangle these two mechanisms based on widely available bulk sequencing data, where sequences from individual cells are intermixed and, thus, the cell lineage tree of the tumor cannot be resolved. Here we present a method that can simultaneously estimate the cell turnover rate and the rate of mutations from bulk sequencing data. Our method works by simulating tumor growth and finding the parameters with which the observed data can be reproduced with maximum likelihood. Applying this method to a real tumor sample, we find that both the mutation rate and the frequency of death may be high.https://doi.org/10.1371/journal.pcbi.1010048 |
| spellingShingle | Gergely Tibély Dominik Schrempf Imre Derényi Gergely J Szöllősi Distinguishing excess mutations and increased cell death based on variant allele frequencies. PLoS Computational Biology |
| title | Distinguishing excess mutations and increased cell death based on variant allele frequencies. |
| title_full | Distinguishing excess mutations and increased cell death based on variant allele frequencies. |
| title_fullStr | Distinguishing excess mutations and increased cell death based on variant allele frequencies. |
| title_full_unstemmed | Distinguishing excess mutations and increased cell death based on variant allele frequencies. |
| title_short | Distinguishing excess mutations and increased cell death based on variant allele frequencies. |
| title_sort | distinguishing excess mutations and increased cell death based on variant allele frequencies |
| url | https://doi.org/10.1371/journal.pcbi.1010048 |
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