HaploDMF: viral haplotype reconstruction from long reads via deep matrix factorization.

Abstract

Lacking strict proofreading mechanisms, many RNA viruses can generate progeny with slightly changed genomes. Being able to characterize highly similar genomes (i.e. haplotypes) in one virus population helps study the viruses' evolution and their interactions with the host/other microbes. High-throughput sequencing data has become the major source for characterizing viral populations. However, the inherent limitation on read length by next-generation sequencing makes complete haplotype reconstruction difficult. In this work, we present a new tool named HaploDMF that can construct complete haplotypes using third-generation sequencing (TGS) data. HaploDMF utilizes a deep matrix factorization model with an adapted loss function to learn latent features from aligned reads automatically. The latent features are then used to cluster reads of the same haplotype. Unlike existing tools whose performance can be affected by the overlap size between reads, HaploDMF is able to achieve highly robust performance on data with different coverage, haplotype number and error rates. In particular, it can generate more complete haplotypes even when the sequencing coverage drops in the middle. We benchmark HaploDMF against the state-of-the-art tools on simulated and real sequencing TGS data on different viruses. The results show that HaploDMF competes favorably against all others. The source code and the documentation of HaploDMF are available at https://github.com/dhcai21/HaploDMF. Supplementary data are available at Bioinformatics online.