Title
Sparsely correlated hidden Markov models with application to genome-wide location studies.
Abstract
Multiply correlated datasets have become increasingly common in genome-wide location analysis of regulatory proteins and epigenetic modifications. Their correlation can be directly incorporated into a statistical model to capture underlying biological interactions, but such modeling quickly becomes computationally intractable.We present sparsely correlated hidden Markov models (scHMM), a novel method for performing simultaneous hidden Markov model (HMM) inference for multiple genomic datasets. In scHMM, a single HMM is assumed for each series, but the transition probability in each series depends on not only its own hidden states but also the hidden states of other related series. For each series, scHMM uses penalized regression to select a subset of the other data series and estimate their effects on the odds of each transition in the given series. Following this, hidden states are inferred using a standard forward-backward algorithm, with the transition probabilities adjusted by the model at each position, which helps retain the order of computation close to fitting independent HMMs (iHMM). Hence, scHMM is a collection of inter-dependent non-homogeneous HMMs, capable of giving a close approximation to a fully multivariate HMM fit. A simulation study shows that scHMM achieves comparable sensitivity to the multivariate HMM fit at a much lower computational cost. The method was demonstrated in the joint analysis of 39 histone modifications, CTCF and RNA polymerase II in human CD4+ T cells. scHMM reported fewer high-confidence regions than iHMM in this dataset, but scHMM could recover previously characterized histone modifications in relevant genomic regions better than iHMM. In addition, the resulting combinatorial patterns from scHMM could be better mapped to the 51 states reported by the multivariate HMM method of Ernst and Kellis.The scHMM package can be freely downloaded from http://sourceforge.net/p/schmm/ and is recommended for use in a linux environment.
Year
DOI
Venue
2013
10.1093/bioinformatics/btt012
Bioinformatics
Keywords
Field
DocType
data series,hidden state,histone modification,multivariate hmm fit,simultaneous hidden markov model,related series,location study,multivariate hmm method,schmm package,own hidden state,single hmm,markov chains,genomics,chromatin immunoprecipitation,histones,algorithms,genome
Data mining,Regression,Inference,Computer science,Multivariate statistics,Markov chain,Correlation,Statistical model,Bioinformatics,Hidden Markov model,Computation
Journal
Volume
Issue
ISSN
29
5
1367-4811
Citations 
PageRank 
References 
5
0.48
6
Authors
5
Name
Order
Citations
PageRank
Hyungwon Choi1454.79
Damian Fermin260.93
Alexey I Nesvizhskii310910.52
Debashis Ghosh449649.16
Zhaohui Qin528630.63