Capturing diverse microbial sequence with comprehensive and scalable probe design
Hayden C Metsky,
Katherine J. Siddle,
David K Yang,
Aaron E Lin,
Kayla G. Barnes,
Damien C. Tully,
Yasmine R Vieira,
Lauren M Paul,
Amanda L Tan,
Kimberly F Garcia,
Leda A Parham,
Onikepe A Folarin,
Viral Hemorrhagic Fever Consortium,
Todd M Allen,
Fernando A. Bozza,
Thiago Moreno L. Souza,
Scott F Michael,
Daniel J. Park,
Pardis C Sabeti,
Christian B. Matranga
Posted 12 Mar 2018
bioRxiv DOI: 10.1101/279570 (published DOI: 10.1038/s41587-018-0006-x)
Posted 12 Mar 2018
Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa, and implemented it in a publicly available software package. CATCH designs compact probe sets that achieve full coverage of known microbial sequence diversity and that scale well with this diversity. Using CATCH, we designed and synthesized multiple probe sets, including one to capture whole genomes of the 356 viral species known to infect humans, and conducted a rigorous evaluation of their performance. Capture with these probe sets enriched unique viral content on average 18-fold in sequencing libraries from patient and environmental samples and allowed us to assemble viral genomes that we could not otherwise recover. We show that capture accurately reflects co-infections and within-host nucleotide variation, enriches sequence with substantial divergence from the probe sets, and improves detection of viral infections in samples with unknown microbial content. Our work provides a new approach to probe design and evaluation, and demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.
- Downloaded 1,775 times
- Download rankings, all-time:
- Site-wide: 8,983
- In genomics: 981
- Year to date:
- Site-wide: 61,340
- Since beginning of last month:
- Site-wide: 70,334
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 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!