TY  - JOUR
AU  - Äijö, Tarmo
AU  - Huang, Yun
AU  - Mannerström, Henrik
AU  - Chavez, Lukas
AU  - Tsagaratou, Ageliki
AU  - Rao, Anjana
AU  - Lähdesmäki, Harri
TI  - A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways.
JO  - Genome biology
VL  - 17
IS  - 1
SN  - 1474-760X
CY  - London
PB  - BioMed Central
M1  - DKFZ-2017-01550
SP  - 49
PY  - 2016
AB  - 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.
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - 5-Methylcytosine (NLM Chemicals)
KW  - Cytosine (NLM Chemicals)
KW  - DNA (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26975309
C2  - pmc:PMC4792102
DO  - DOI:10.1186/s13059-016-0911-6
UR  - https://inrepo02.dkfz.de/record/125420
ER  -