title: Parsimonious higher-order hidden Markov models for improved array-CGH analysis with applications to Arabidopsis thaliana.
abstract: Array-based comparative genomic hybridization (Array-CGH) is an important technology in molecular biology for the detection of DNA copy number polymorphisms between closely related genomes. Hidden Markov Models (HMMs) are popular tools for the analysis of Array-CGH data, but current methods are only based on first-order HMMs having constrained abilities to model spatial dependencies between measurements of closely adjacent chromosomal regions. Here, we develop parsimonious higher-order HMMs enabling the interpolation between a mixture model ignoring spatial dependencies and a higher-order HMM exhaustively modeling spatial dependencies. We apply parsimonious higher-order HMMs to the analysis of Array-CGH data of the accessions C24 and Col-0 of the model plant Arabidopsis thaliana. We compare these models against first-order HMMs and other existing methods using a reference of known deletions and sequence deviations. We find that parsimonious higher-order HMMs clearly improve the identification of these polymorphisms. Moreover, we perform a functional analysis of identified polymorphisms revealing novel details of genomic differences between C24 and Col-0. Additional model evaluations are done on widely considered Array-CGH data of human cell lines indicating that parsimonious HMMs are also well-suited for the analysis of non-plant specific data. All these results indicate that parsimonious higher-order HMMs are useful for Array-CGH analyses. An implementation of parsimonious higher-order HMMs is available as part of the open source Java library Jstacs (www.jstacs.de/index.php/PHHMM).
authors.affiliation: Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany. seifert@ipk-gatersleben.de
authors.forename: Michael
authors.initials: M
authors.lastname: Seifert
authors.forename: André
authors.initials: A
authors.lastname: Gohr
authors.forename: Marc
authors.initials: M
authors.lastname: Strickert
authors.forename: Ivo
authors.initials: I
authors.lastname: Grosse
mesh_terms: D017360:Arabidopsis / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D015894:Genome, Human; D018745:Genome, Plant; D006801:Humans; D008390:Markov Chains; D011110:Polymorphism, Genetic