Accurate detection of complex structural variations using single-molecule sequencing

Sedlazeck, F. J., Rescheneder, P., Smolka, M., Fang, H., Nattestad, M., von Haeseler, A., Schatz, M. C. (June 2018) Accurate detection of complex structural variations using single-molecule sequencing. Nat Methods, 15 (6). pp. 461-468. ISSN 1548-7091

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URL: https://www.ncbi.nlm.nih.gov/pubmed/29713083
DOI: 10.1038/s41592-018-0001-7

Abstract

Structural variations are the greatest source of genetic variation, but they remain poorly understood because of technological limitations. Single-molecule long-read sequencing has the potential to dramatically advance the field, although high error rates are a challenge with existing methods. Addressing this need, we introduce open-source methods for long-read alignment (NGMLR; https://github.com/philres/ngmlr ) and structural variant identification (Sniffles; https://github.com/fritzsedlazeck/Sniffles ) that provide unprecedented sensitivity and precision for variant detection, even in repeat-rich regions and for complex nested events that can have substantial effects on human health. In several long-read datasets, including healthy and cancerous human genomes, we discovered thousands of novel variants and categorized systematic errors in short-read approaches. NGMLR and Sniffles can automatically filter false events and operate on low-coverage data, thereby reducing the high costs that have hindered the application of long reads in clinical and research settings.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > computers > computer software
CSHL Authors:
Communities: CSHL labs > Schatz lab
Watson School > Publications
Depositing User: Matt Covey
Date: June 2018
Date Deposited: 22 May 2018 16:44
Last Modified: 03 Oct 2019 16:54
PMCID: PMC5990442
Related URLs:
URI: https://repository.cshl.edu/id/eprint/36564

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