Reconstructing components of a genomic mixture from data obtained by means of DNA sequencing is a challenging problem encountered in a variety of applications including single individual haplotyping and studies of viral communities. High-throughput DNA sequencing platforms oversample mixture components to provide massive amounts of reads whose relative positions can be determined by mapping the reads to a known reference genome; assembly of the components, however, requires discovery of the reads' origin – an NP-hard problem that the existing methods struggle to solve with the required level of accuracy. In this paper, we present a learning framework based on a graph auto-encoder designed to exploit structural properties of sequencing data. The algorithm is a neural network which essentially trains to ignore sequencing errors and infers the posterior probabilities of the origin of sequencing reads. Mixture components are then reconstructed by finding consensus of the reads determined to originate from the same genomic component. Results on realistic synthetic as well as experimental data demonstrate that the proposed framework reliably assembles haplotypes and reconstructs viral communities, often significantly outperforming state-of-the-art techniques. Source codes, datasets and supplementary document are available at https://github.com/WuLoli/GAEseq.
Published Date: 2020-06-02
Registration: ISSN 2374-3468 (Online) ISSN 2159-5399 (Print) ISBN 978-1-57735-835-0 (10 issue set)
Copyright: Published by AAAI Press, Palo Alto, California USA Copyright © 2020, Association for the Advancement of Artificial Intelligence All Rights Reserved