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A generative model to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications.


Allows integrative analysis of different oxi-mC data sets with experimental parameters and arbitrary, complex experimental designs. The method is applicable in analysis of genome-wide, reduced representation and targeted bisulphite sequencing data. Comparisons to existing methods demonstrated that LuxGLM has similar or better differential methylation detection performance than existing tools on BS-seq data. Analysis of simulated data showed that LuxGLM can provide accurate estimates of DNA methylation modifications even when confounding factors are present. Moreover, for oxi-mC species measured using complex experimental designs, LuxGLM is superior in differential methylation analysis when compared with existing methods.