Accurate detection of complex structural variations using single-molecule sequencing.

TitleAccurate detection of complex structural variations using single-molecule sequencing.
Publication TypeJournal Article
Year of Publication2018
AuthorsSedlazeck, FJ, Rescheneder, P, Smolka, M, Fang, H, Nattestad, M, von Haeseler, A, Schatz, MC
JournalNat Methods
Volume15
Issue6
Pagination461-468
Date Published2018 Jun
ISSN1548-7105
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.

DOI10.1038/s41592-018-0001-7
Alternate JournalNat. Methods
PubMed ID29713083
PubMed Central IDPMC5990442
Grant ListR01 HG006677 / HG / NHGRI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States