PT  - JOURNAL ARTICLE
AU  - Fritz J. Sedlazeck
AU  - Philipp Rescheneder
AU  - Moritz Smolka
AU  - Han Fang
AU  - Maria Nattestad
AU  - Arndt von Haeseler
AU  - Michael C. Schatz
TI  - Accurate detection of complex structural variations using single molecule sequencing
AID  - 10.1101/169557
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 169557
4099  - http://biorxiv.org/content/early/2017/07/28/169557.short
4100  - http://biorxiv.org/content/early/2017/07/28/169557.full
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.