VIPR HMM: a hidden Markov model for detecting recombination with microbial detection microarrays

摘要

Motivation: Current methods in diagnostic microbiology typically focus on the detection of a single genomic locus or protein in a candidate agent. The presence of the entire microbe is then inferred from this isolated result. Problematically, the presence of recombination in microbial genomes would go undetected unless other genomic loci or protein components were specifically assayed. Microarrays lend themselves well to the detection of multiple loci from a given microbe; furthermore, the inherent nature of microarrays facilitates highly parallel interrogation of multiple microbes. However, none of the existing methods for analyzing diagnostic microarray data has the capacity to specifically identify recombinant microbes. In previous work, we developed a novel algorithm, VIPR, for analyzing diagnostic microarray data. Results: We have expanded upon our previous implementation of VIPR by incorporating a hidden Markov model (HMM) to detect recombinant genomes. We trained our HMM on a set of non-recombinant parental viruses and applied our method to 11 recombinant alphaviruses and 4 recombinant flaviviruses hybridized to a diagnostic microarray in order to evaluate performance of the HMM. VIPR HMM correctly identified 95% of the 62 inter-species recombination breakpoints in the validation set and only two false-positive breakpoints were predicted. This study represents the first description and validation of an algorithm capable of detecting recombinant viruses based on diagnostic microarray hybridization patterns.