Jeffrey Yuan | Search bioRxiv

bioRxiv2016

Assembly of Long Error-Prone Reads Using de Bruijn Graphs

The recent breakthroughs in assembling long error-prone reads (such as reads generated by Single Molecule Real Time technology) were based on the overlap-layout-consensus approach and did not utilize the strengths of the alternative de Bruijn graph approach to genome assembly. Moreover, these studies often assume that applications of the de Bruijn graph approach are limited to short and accurate reads and that the overlap-layout-consensus approach is the only practical paradigm for assembling long error-prone reads. Below we show how to generalize de Bruijn graphs to assemble long error-prone reads and describe the ABruijn assembler, which results in more accurate genome reconstructions than the existing state-of-the-art algorithms.

Bioinformatics↗

bioRxiv2015

Frequency and complexity of de novo structural mutation in autism

Genetic studies of Autism Spectrum Disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variation (SV) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping and de novo assembly to genome sequencing of 235 subjects, 71 cases, 26 sibling controls and their parents, we present an atlas of 1.2 million SVs (5,213/genome), comprising 11 different classes. We demonstrate a high diversity of de novo mutations, a majority of which were undetectable by previous methods. In addition, we observe complex mutation clusters where combinations of de novo SVs, nucleotide substitutions and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%). Genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs but not an elevated rate of genome rearrangement.

Genomics↗