Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,655 bioRxiv papers from 298,484 authors.
The mutational profile and clonal landscape of the inflammatory bowel disease affected colon
Rebecca E. McIntyre,
Mathijs A Sanders,
Michael R. Stratton,
Peter J. Campbell,
Carl A. Anderson
Posted 11 Nov 2019
bioRxiv DOI: 10.1101/832014
Posted 11 Nov 2019
Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with increased risk of gastrointestinal cancers but our understanding of the effects of IBD on the mutational profile and clonal structure of the colon is limited. Here, we isolated and whole-genome sequenced 370 colonic crypts from 45 IBD patients, and compared these to 413 crypts from 41 non-IBD controls. We estimated the base substitution rate of affected colonic epithelial cells to be doubled after IBD onset. This change was primarily driven by acceleration of mutational processes ubiquitously observed in normal colon, and we did not detect an IBD-specific mutational process. In contrast to the normal colon, where clonal expansions outside the confines of the crypt are rare, we observed widespread millimeter-scale clonal expansions. We also found that non-synonymous mutations in ARID1A, PIGR and ZC3H12A, and genes in the interleukin 17 and Toll-like receptor pathways, were under positive selection in colonic crypts from IBD patients. With the exception of ARID1A, these genes and pathways have not been previously associated with cancer risk. Our results provide new insights into the consequences of chronic intestinal inflammation on the mutational profile and clonal structure of colonic epithelia and point to potential therapeutic targets for IBD.
- Downloaded 893 times
- Download rankings, all-time:
- Site-wide: 9,385 out of 67,655
- In genetics: 695 out of 3,803
- Year to date:
- Site-wide: 2,449 out of 67,655
- Since beginning of last month:
- Site-wide: 88 out of 67,655
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 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!