Differentially DNA methylated regions (DMRs) inform on the role of epigenetic changes in cancer. We present Rocker-meth, a new computational method exploiting a heterogeneous hidden Markov model to detect DMRs across multiple experimental platforms. Through an extensive comparative study, we first demonstrate Rocker-meth excellent performance on synthetic data. Its application to more than 6,000 methylation profiles across 14 tumor types provides a comprehensive catalog of tumor type-specific and shared DMRs, and agnostically identifies cancer-related partially methylated domains (PMD). In depth integrative analysis including orthogonal omics shows the enhanced ability of Rocker-meth in recapitulating known associations, further uncovering the pan-cancer relationship between DNA hypermethylation and transcription factor deregulation depending on the baseline chromatin state. Finally, we demonstrate the utility of the catalog for the study of colorectal cancer single-cell DNA-methylation data.

Charting differentially methylated regions in cancer with Rocker-meth / Benelli, M.; Franceschini, G. M.; Magi, A.; Romagnoli, D.; Biagioni, C.; Migliaccio, I.; Malorni, L.; Demichelis, F.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 2021/4:1(2021), pp. 124901-124915. [10.1038/s42003-021-02761-3]

Charting differentially methylated regions in cancer with Rocker-meth

Benelli M.;Franceschini G. M.;Demichelis F.
2021-01-01

Abstract

Differentially DNA methylated regions (DMRs) inform on the role of epigenetic changes in cancer. We present Rocker-meth, a new computational method exploiting a heterogeneous hidden Markov model to detect DMRs across multiple experimental platforms. Through an extensive comparative study, we first demonstrate Rocker-meth excellent performance on synthetic data. Its application to more than 6,000 methylation profiles across 14 tumor types provides a comprehensive catalog of tumor type-specific and shared DMRs, and agnostically identifies cancer-related partially methylated domains (PMD). In depth integrative analysis including orthogonal omics shows the enhanced ability of Rocker-meth in recapitulating known associations, further uncovering the pan-cancer relationship between DNA hypermethylation and transcription factor deregulation depending on the baseline chromatin state. Finally, we demonstrate the utility of the catalog for the study of colorectal cancer single-cell DNA-methylation data.
2021
1
Benelli, M.; Franceschini, G. M.; Magi, A.; Romagnoli, D.; Biagioni, C.; Migliaccio, I.; Malorni, L.; Demichelis, F.
Charting differentially methylated regions in cancer with Rocker-meth / Benelli, M.; Franceschini, G. M.; Magi, A.; Romagnoli, D.; Biagioni, C.; Migliaccio, I.; Malorni, L.; Demichelis, F.. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - 2021/4:1(2021), pp. 124901-124915. [10.1038/s42003-021-02761-3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/336323
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