title: Prediction of multi-drug resistance transporters using a novel sequence analysis method.
abstract: There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequence similarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.
authors.affiliation: Biological Sciences, Pacific Northwest National Laboratory, Washington, WA, 99352, USA; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: McDermott
authors.affiliation: National Security Divisions, Pacific Northwest National Laboratory, Washington, WA, 99352, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Bruillard
authors.affiliation: Biological Sciences, Pacific Northwest National Laboratory, Washington, WA, 99352, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Overall
authors.affiliation: National Security Divisions, Pacific Northwest National Laboratory, Washington, WA, 99352, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Gosink
authors.affiliation: Biological Sciences, Pacific Northwest National Laboratory, Washington, WA, 99352, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Lindemann
keywords: antibiotic resistance; bacteria; linguistics; machine learning; microbiome; multidrug resistance transporters; protein function