Abstract
A multi-assembly problem asks to reconstruct multiple genomic sequences from mixed reads sequenced from all of them. Standard formulations of such problems model a solution as a path cover in a directed acyclic graph, namely a set of paths that together cover all vertices of the graph. Since multi-assembly problems admit multiple solutions in practice, we consider an approach commonly used in standard genome assembly: output only partial solutions (contigs, or safe paths), that appear in all path cover solutions. We study constrained path covers, a restriction on the path cover solution that incorporate practical constraints arising in multi-assembly problems. We give efficient algorithms finding all maximal safe paths for constrained path covers. We compute the safe paths of splicing graphs constructed from transcript annotations of different species. Our algorithms run in less than 15 seconds per species and report RNA contigs that are over 99% precise and are up to 8 times longer than unitigs. Moreover, RNA contigs cover over 70% of the transcripts and their coding sequences in most cases. With their increased length to unitigs, high precision, and fast construction time, maximal safe paths can provide a better base set of sequences for transcript assembly programs.
Highlights
M ANY real-world problems require to reconstruct an unknown object from partial data observed from it
Genome assembly is a typical instance of such problem in Bioinformatics: given a set of high-throughput sequencing reads obtained from some genomic sequence, we need to reconstruct the sequence from which the reads originate
We considered a natural generalization of the classical problem of minimum path cover, including more practical constraints, which we called constrained path covers
Summary
M ANY real-world problems require to reconstruct an unknown object from partial data observed from it. Genome assembly is a typical instance of such problem in Bioinformatics: given a set of high-throughput sequencing reads obtained from some genomic sequence, we need to reconstruct the sequence from which the reads originate. A major issue in such problems is that multiple solutions (reconstructions) can explain the observed data, making it difficult to distinguish the correct solution. As such, reporting one arbitrary solution may lead to an incorrect answer to the problem. An established way of coping with this issue is to report only partial solutions about which we are “confident” that they are correct. Stateof-the-art genome assemblers do not output entire chromosomes, but only contigs, namely genomic fragments that are promised to occur in the original genome
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