LuxHMM: DNA methylation analysis with genome segmentation via hidden Markov model

BACKGROUND: DNA methylation plays an important role in studying the epigenetics of various biological processes including many diseases. Although differential methylation of individual cytosines can be informative, given that methylation of neighboring CpGs are typically correlated, analysis of differentially methylated regions is often of more interest. RESULTS: We have developed a probabilistic method and software, LuxHMM, that uses hidden Markov model (HMM) to segment the genome into regions and a Bayesian regression model, which allows handling of multiple covariates, to infer differential methylation of regions. Moreover, our model includes experimental parameters that describe the underlying biochemistry in bisulfite sequencing and model inference is done using either variational inference for efficient genome-scale analysis or Hamiltonian Monte Carlo (HMC). CONCLUSIONS: Analyses of real and simulated bisulfite sequencing data demonstrate the competitive performance of LuxHMM compared with other published differential methylation analysis methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-023-05174-7.