Single cell tri-channel-processing reveals structural variation landscapes and complex rearrangement processes
Ashley D. Sanders,
M. Alexandra C.C. van Vliet,
Joachim B. Kunz,
Balca R. Mardin,
Jan O. Korbel
Posted 21 Nov 2019
bioRxiv DOI: 10.1101/849604
Posted 21 Nov 2019
Structural variation (SV), where rearrangements delete, duplicate, invert or translocate DNA segments, is a major source of somatic cell variation. It can arise in rapid bursts, mediate genetic heterogeneity, and dysregulate cancer-related pathways. The challenge to systematically discover SVs in single cells remains unsolved, with copy-neutral and complex variants typically escaping detection. We developed single cell tri-channel-processing (scTRIP), a computational framework that jointly integrates read depth, template strand and haplotype phase to comprehensively discover SVs in single cells. We surveyed SV landscapes of 565 single cell genomes, including transformed epithelial cells and patient-derived leukemic samples, and discovered abundant SV classes including inversions, translocations and complex DNA rearrangements mediating oncogenic dysregulation. We dissected the 'molecular karyotype' of the leukemic samples and examined their clonal structure. Different from prior methods, scTRIP also enabled direct detection and discrimination of SV mutational processes in individual somatic cells, including breakage-fusion-bridge cycles. scTRIP will facilitate studies of clonal evolution, genetic mosaicism and somatic SV formation, and could improve disease classification for precision medicine.
- Downloaded 454 times
- Download rankings, all-time:
- Site-wide: 37,514 out of 94,912
- In genomics: 3,546 out of 5,955
- Year to date:
- Site-wide: 29,342 out of 94,912
- Since beginning of last month:
- Site-wide: 49,699 out of 94,912
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!