Genome reassembly with high-throughput sequencing data

Abstract

MotivationRecent studies in genomics have highlighted the significance of structural variation in determining individual variation. Current methods for identifying structural variation, however, are predominantly focused on either assembling whole genomes from scratch, or identifying the relatively small changes between a genome and a reference sequence. While significant progress has been made in recent years on both de novo assembly and resequencing (read mapping) methods, few attempts have been made to bridge the gap between them.ResultsIn this paper, we present a computational method for incorporating a reference sequence into an assembly algorithm. We propose a novel graph construction that builds upon the well-known de Bruijn graph to incorporate the reference, and describe a simple algorithm, based on iterative message passing, which uses this information to significantly improve assembly results. We validate our method by applying it to a series of 5 Mb simulation genomes derived from both mammalian and bacterial references. The results of applying our method to this simulation data are presented along with a discussion of the benefits and drawbacks of this technique.

De Novo Structural Variations of Escherichia coli Detected by Nanopore Long-Read Sequencing

“…In addition, SV detection using long-read tools is also affected by the sequencing depth and SV types, for example, high sequencing depth could even reduce the accuracy of some tools ( Luan et al 2020 ; Dierckxsens et al 2021 ; Lesack et al 2022 ). Similarly, long-read tools also detect inversions unsatisfactorily, which also needs facilitation of other algorithms ( Parrish et al 2013 ).…”

PopIns: population-scale detection of novel sequence insertions

“…This issue is most pronounced in de novo whole-genome assembly strategies and, thus, has previously been addressed. Parrish et al (Parrish et al, 2013) suggested a reference-guided whole-genome assembly approach that makes the results of several samples more compatible. Iqbal et al (Iqbal et al, 2012) developed Cortex, a program that rigorously assembles the whole genomes of several individuals at the same time based on colored de-Bruijn graphs.…”