Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,429 bioRxiv papers from 307,558 authors.
Whole Genome Doubling mitigates Muller's Ratchet in Cancer Evolution
Thomas B.K. Watkins,
Sally M Dewhurst,
Nicolai J. Birkbak,
Gareth A. Wilson,
on behalf of TRACERx Consortium,
Posted 07 Jan 2019
bioRxiv DOI: 10.1101/513457
Posted 07 Jan 2019
Whole genome doubling (WGD) is a prevalent macro-evolutionary event in cancer, involving a doubling of the entire chromosome complement. However, despite its prevalence and clinical prognostic relevance, the evolutionary selection pressures for WGD have not been investigated. Here, we explored whether WGD may act to mitigate the irreversible, inexorable ratchet-like, accumulation of deleterious mutations in essential genes. Utilizing 1050 tumor regions from 816 non-small cell lung cancers (NSCLC), we temporally dissect mutations to determine their temporal acquisition in relation to WGD. We find evidence for strong negative selection against homozygous loss of essential cancer genes prior to WGD. However, mutations in essential genes occurring after duplication were not subject to significant negative selection, consistent with WGD providing a buffering effect, decreasing the likelihood of homozygous loss. Finally, we demonstrate that loss of heterozygosity and temporal dissection of mutations can be exploited to identify signals of positive selection in lung, breast, colorectal cancer and other cancer types, enabling the elucidation of novel tumour suppressor genes and a deeper characterization of known cancer genes.
- Downloaded 1,424 times
- Download rankings, all-time:
- Site-wide: 4,596 out of 70,438
- In genomics: 816 out of 4,710
- Year to date:
- Site-wide: 4,201 out of 70,438
- Since beginning of last month:
- Site-wide: 5,077 out of 70,438
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!