A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways
Year: 2016
Type: article
Abstract: We present a generative model, Lux, 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. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.
Source: Genome biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,490
Funders: Cancer Research Institute, Cancer Prevention and Research Institute of Texas, Alexander von Humboldt-Stiftung, Leukemia and Lymphoma Society, Deutsches Krebsforschungszentrum, Academy of Finland, Aalto-Yliopisto, Turun Yliopisto, Åbo Akademi, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: FACSAria II Cell Sorter, Role of TET proteins in myeloid malignancies, G123601971, G2045344024, G2188863825, G2284450968, G3334505115, Role of TET Proteins in ES Cell Pluripotency and Function, Recruitment of First-Time, Tenure-Track Faculty Members, Regulated Accessibility of a cytokine gene locus., G7976538385, G8026658578
OpenAlex ID: W2301629837