PHHMM

by Michael Seifert, André Gohr, Marc Strickert, and Ivo Grosse

Description

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 also 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.

Paper

The paper Parsimonious higher-order Hidden Markov Models for improved Array-CGH analysis with applications to Arabidopsis thaliana has been published in PloS Comp Biol.

Download

• Parsimonious HMMs: A ZIP file including a JAR file for analyzing data sets by parsimonious higher-order HMMs and examples for the Arabidopsis and the human cell lines data

Related Projects

• DSHMM: exploiting prior knowledge and gene distances in the analysis of tumor expression profiles
• SHMM: utilizing gene-pair orientations for improved analysis of ChIP-chip promoter array data
• MeDIP-HMM: HMM-based analysis of DNA methylation profiles
• HMM Book: Hidden Markov Models with Applications in Computational Biology