RT Journal Article
SR Electronic
T1 Accurate detection of complex structural variations using single molecule sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 169557
DO 10.1101/169557
A1 Fritz J. Sedlazeck
A1 Philipp Rescheneder
A1 Moritz Smolka
A1 Han Fang
A1 Maria Nattestad
A1 Arndt von Haeseler
A1 Michael C. Schatz
YR 2017
UL http://biorxiv.org/content/early/2017/07/28/169557.abstract
AB Structural variations (SVs) are the largest source of genetic variation, but remain poorly understood because of limited genomics technology. Single molecule long read sequencing from Pacific Biosciences and Oxford Nanopore has the potential to dramatically advance the field, although their high error rates challenge existing methods. Addressing this need, we introduce open-source methods for long read alignment (NGMLR, https://github.com/philres/ngmlr) and SV identification (Sniffles, https://github.com/fritzsedlazeck/Sniffles) that enable unprecedented SV sensitivity and precision, including within repeat-rich regions and of complex nested events that can have significant impact on human disorders. Examining several datasets, including healthy and cancerous human genomes, we discover thousands of novel variants using long reads and categorize systematic errors in short-read approaches. NGMLR and Sniffles are further able to automatically filter false events and operate on low amounts of coverage to address the cost factor that has hindered the application of long reads in clinical and research settings.