Accurate Detection of Complex Structural Variations Using Single-molecule Sequencing

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2018 May 2

PMID 29713083

Citations 746

Authors

Fritz J Sedlazeck

Philipp Rescheneder

Moritz Smolka

Han Fang

Maria Nattestad

Arndt von Haeseler

Michael C Schatz

Affiliations

Soon will be listed here.

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.

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