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, Matteo; Franceschini, Gian Marco; Magi, Alberto; Romagnoli, Dario; Biagioni, Chiara; Migliaccio, Ilenia; Malorni, Luca; Demichelis, Francesca. - In: COMMUNICATIONS BIOLOGY. - ISSN 2399-3642. - ELETTRONICO. - 4:(2021), pp. 0-0. [10.1038/s42003-021-02761-3]

Charting differentially methylated regions in cancer with Rocker-meth

Benelli, Matteo;Magi, Alberto;Romagnoli, Dario;Biagioni, Chiara;
2021

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.
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Benelli, Matteo; Franceschini, Gian Marco; Magi, Alberto; Romagnoli, Dario; Biagioni, Chiara; Migliaccio, Ilenia; Malorni, Luca; Demichelis, Francesca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1247179
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