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
Date Published2018 06
KeywordsDNA Mutational Analysis, Genome, Human, Genomics, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA

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; ) and structural variant identification (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.

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