title: Alignment-free $d_2^*$ oligonucleotide frequency dissimilarity measure improves prediction of hosts from metagenomically-derived viral sequences.
abstract: Viruses and their host genomes often share similar oligonucleotide frequency (ONF) patterns, which can be used to predict the host of a given virus by finding the host with the greatest ONF similarity. We comprehensively compared 11 ONF metrics using several k-mer lengths for predicting host taxonomy from among ∼32 000 prokaryotic genomes for 1427 virus isolate genomes whose true hosts are known. The background-subtracting measure [Formula: see text] at k = 6 gave the highest host prediction accuracy (33%, genus level) with reasonable computational times. Requiring a maximum dissimilarity score for making predictions (thresholding) and taking the consensus of the 30 most similar hosts further improved accuracy. Using a previous dataset of 820 bacteriophage and 2699 bacterial genomes, [Formula: see text] host prediction accuracies with thresholding and consensus methods (genus-level: 64%) exceeded previous Euclidian distance ONF (32%) or homology-based (22-62%) methods. When applied to metagenomically-assembled marine SUP05 viruses and the human gut virus crAssphage, [Formula: see text]-based predictions overlapped (i.e. some same, some different) with the previously inferred hosts of these viruses. The extent of overlap improved when only using host genomes or metagenomic contigs from the same habitat or samples as the query viruses. The [Formula: see text] ONF method will greatly improve the characterization of novel, metagenomic viruses.
authors.affiliation: Department of Biological Sciences, University of Southern California, 3616 Trousdale Pkwy Los, Angeles, CA 90089, USA ahlgren@usc.edu.
authors.forename: Nathan A
authors.identifier: 0000-0001-7617-4435
authors.initials: NA
authors.lastname: Ahlgren
authors.affiliation: Molecular and Computational Biology Program, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Molecular and Computational Biology Program, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA.
authors.forename: Yang Young
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Biological Sciences, University of Southern California, 3616 Trousdale Pkwy Los, Angeles, CA 90089, USA.
authors.forename: Jed A
authors.initials: JA
authors.lastname: Fuhrman
authors.affiliation: Department of Biological Sciences, University of Southern California, 3616 Trousdale Pkwy Los, Angeles, CA 90089, USA.|Molecular and Computational Biology Program, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA.|Center for Computational Systems Biology, Fudan University, Shanghai 200433, China.
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
mesh_terms: D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000821:virology; D001435:Bacteriophages / Q000145:classification / Q000235:genetics*; D001483:Base Sequence; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000821:virology; D016680:Genome, Bacterial; D015894:Genome, Human; D016679:Genome, Viral; D006801:Humans; D056186:Metagenomics; D009841:Oligonucleotides / Q000737:chemistry* / Q000235:genetics; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid
chemical_list: D009841:Oligonucleotides