Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles
DNA methylation is recognized as one of several epigenetic regulators of gene expression and as potential driver of carcinogenesis through gene-silencing of tumor suppressors and activation of oncogenes. However, abnormal methylation, even of promoter regions, does not necessarily alter gene express...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2018, May 3
|
| In: |
Epigenetics
Year: 2018, Volume: 13, Issue: 4, Pages: 386-397 |
| ISSN: | 1559-2308 |
| DOI: | 10.1080/15592294.2018.1460034 |
| Online Access: | Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1080/15592294.2018.1460034 Verlag, Pay-per-use, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140810/ 
|
| Author Notes: | Hagen Klett, Yesilda Balavarca, Reka Toth, Biljana Gigic, Nina Habermann, Dominique Scherer, Petra Schrotz-King, Alexis Ulrich, Peter Schirmacher, Esther Herpel, Hermann Brenner, Cornelia M. Ulrich, Karin B. Michels, Hauke Busch and Melanie Boerries |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1583626352 | ||
| 003 | DE-627 | ||
| 005 | 20220815052717.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 181112s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/15592294.2018.1460034 |2 doi | |
| 035 | |a (DE-627)1583626352 | ||
| 035 | |a (DE-576)513626352 | ||
| 035 | |a (DE-599)BSZ513626352 | ||
| 035 | |a (OCoLC)1341023451 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Klett, Hagen |d 1988- |e VerfasserIn |0 (DE-588)1171172885 |0 (DE-627)1040411819 |0 (DE-576)513626972 |4 aut | |
| 245 | 1 | 0 | |a Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles |c Hagen Klett, Yesilda Balavarca, Reka Toth, Biljana Gigic, Nina Habermann, Dominique Scherer, Petra Schrotz-King, Alexis Ulrich, Peter Schirmacher, Esther Herpel, Hermann Brenner, Cornelia M. Ulrich, Karin B. Michels, Hauke Busch and Melanie Boerries |
| 264 | 1 | |c 2018, May 3 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 12.11.2018 | ||
| 520 | |a DNA methylation is recognized as one of several epigenetic regulators of gene expression and as potential driver of carcinogenesis through gene-silencing of tumor suppressors and activation of oncogenes. However, abnormal methylation, even of promoter regions, does not necessarily alter gene expression levels, especially if the gene is already silenced, leaving the exact mechanisms of methylation unanswered. Using a large cohort of matching DNA methylation and gene expression samples of colorectal cancer (CRC; n = 77) and normal adjacent mucosa tissues (n = 108), we investigated the regulatory role of methylation on gene expression. We show that on a subset of genes enriched in common cancer pathways, methylation is significantly associated with gene regulation through gene-specific mechanisms. We built two classification models to infer gene regulation in CRC from methylation differences of tumor and normal tissues, taking into account both gene-silencing and gene-activation effects through hyper- and hypo-methylation of CpGs. The classification models result in high prediction performances in both training and independent CRC testing cohorts (0.92<AUC<0.97) as well as in individual patient data (average AUC = 0.82), suggesting a robust interplay between methylation and gene regulation. Validation analysis in other cancerous tissues resulted in lower prediction performances (0.69<AUC<0.90); however, it identified genes that share robust dependencies across cancerous tissues. In conclusion, we present a robust classification approach that predicts the gene-specific regulation through DNA methylation in CRC tissues with possible transition to different cancer entities. Furthermore, we present HMGA1 as consistently associated with methylation across cancers, suggesting a potential candidate for DNA methylation targeting cancer therapy. | ||
| 700 | 1 | |a Balavarca, Yesilda |e VerfasserIn |0 (DE-588)1097307670 |0 (DE-627)857146181 |0 (DE-576)468287434 |4 aut | |
| 700 | 1 | |a Toth, Reka |e VerfasserIn |0 (DE-588)112408469X |0 (DE-627)87780947X |0 (DE-576)482287977 |4 aut | |
| 700 | 1 | |a Gigić, Biljana |d 1978- |e VerfasserIn |0 (DE-588)1124096310 |0 (DE-627)877817561 |0 (DE-576)482295201 |4 aut | |
| 700 | 1 | |a Habermann, Nina |d 1979- |e VerfasserIn |0 (DE-588)140915532 |0 (DE-627)703827960 |0 (DE-576)321344626 |4 aut | |
| 700 | 1 | |a Scherer, Dominique |d 1978- |e VerfasserIn |0 (DE-588)140126090 |0 (DE-627)616036647 |0 (DE-576)314697233 |4 aut | |
| 700 | 1 | |a Schrotz-King, Petra |e VerfasserIn |0 (DE-588)1078258066 |0 (DE-627)838209327 |0 (DE-576)450367118 |4 aut | |
| 700 | 1 | |a Ulrich, Alexis |e VerfasserIn |0 (DE-588)1022952226 |0 (DE-627)717337847 |0 (DE-576)177315083 |4 aut | |
| 700 | 1 | |a Schirmacher, Peter |d 1961- |e VerfasserIn |0 (DE-588)1020440112 |0 (DE-627)691221197 |0 (DE-576)360427448 |4 aut | |
| 700 | 1 | |a Herpel, Esther |d 1973- |e VerfasserIn |0 (DE-588)12965227X |0 (DE-627)476593662 |0 (DE-576)297767984 |4 aut | |
| 700 | 1 | |a Brenner, Hermann |e VerfasserIn |0 (DE-588)1020516445 |0 (DE-627)691247005 |0 (DE-576)360642136 |4 aut | |
| 700 | 1 | |a Ulrich, Cornelia |d 1967- |e VerfasserIn |0 (DE-588)1045797030 |0 (DE-627)775130133 |0 (DE-576)399253289 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Epigenetics |d Austin, Tex. : Landes Bioscience, 2006 |g 13(2018), 4, Seite 386-397 |h Online-Ressource |w (DE-627)516805320 |w (DE-600)2248598-3 |w (DE-576)321221699 |x 1559-2308 |7 nnas |a Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles |
| 773 | 1 | 8 | |g volume:13 |g year:2018 |g number:4 |g pages:386-397 |g extent:12 |a Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/15592294.2018.1460034 |x Verlag |x Resolving-System |z Pay-per-use |3 Volltext |
| 856 | 4 | 0 | |u https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140810/ |x Verlag |z Pay-per-use |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20181112 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 1045797030 |a Ulrich, Cornelia |m 1045797030:Ulrich, Cornelia |d 50000 |e 50000PU1045797030 |k 0/50000/ |p 12 | ||
| 998 | |g 1020516445 |a Brenner, Hermann |m 1020516445:Brenner, Hermann |d 850000 |d 851600 |d 50000 |e 850000PB1020516445 |e 851600PB1020516445 |e 50000PB1020516445 |k 0/850000/ |k 1/850000/851600/ |k 0/50000/ |p 11 | ||
| 998 | |g 12965227X |a Herpel, Esther |m 12965227X:Herpel, Esther |d 910000 |d 912000 |e 910000PH12965227X |e 912000PH12965227X |k 0/910000/ |k 1/910000/912000/ |p 10 | ||
| 998 | |g 1020440112 |a Schirmacher, Peter |m 1020440112:Schirmacher, Peter |d 910000 |d 912000 |e 910000PS1020440112 |e 912000PS1020440112 |k 0/910000/ |k 1/910000/912000/ |p 9 | ||
| 998 | |g 1022952226 |a Ulrich, Alexis |m 1022952226:Ulrich, Alexis |d 910000 |d 910200 |e 910000PU1022952226 |e 910200PU1022952226 |k 0/910000/ |k 1/910000/910200/ |p 8 | ||
| 998 | |g 1078258066 |a Schrotz-King, Petra |m 1078258066:Schrotz-King, Petra |p 7 | ||
| 998 | |g 140126090 |a Scherer, Dominique |m 140126090:Scherer, Dominique |d 910000 |d 999701 |e 910000PS140126090 |e 999701PS140126090 |k 0/910000/ |k 1/910000/999701/ |p 6 | ||
| 998 | |g 140915532 |a Habermann, Nina |m 140915532:Habermann, Nina |d 910000 |e 910000PH140915532 |k 0/910000/ |p 5 | ||
| 998 | |g 1124096310 |a Gigić, Biljana |m 1124096310:Gigić, Biljana |d 910000 |d 910200 |e 910000PG1124096310 |e 910200PG1124096310 |k 0/910000/ |k 1/910000/910200/ |p 4 | ||
| 998 | |g 112408469X |a Toth, Reka |m 112408469X:Toth, Reka |d 910000 |e 910000PT112408469X |k 0/910000/ |p 3 | ||
| 998 | |g 1097307670 |a Balavarca, Yesilda |m 1097307670:Balavarca, Yesilda |p 2 | ||
| 999 | |a KXP-PPN1583626352 |e 3032053145 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title":"Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles","title_sort":"Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"eki":["1583626352"],"doi":["10.1080/15592294.2018.1460034"]},"physDesc":[{"extent":"12 S."}],"relHost":[{"disp":"Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profilesEpigenetics","type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 29.01.26"],"pubHistory":["1.2006 -"],"part":{"volume":"13","year":"2018","text":"13(2018), 4, Seite 386-397","issue":"4","pages":"386-397","extent":"12"},"language":["eng"],"origin":[{"dateIssuedDisp":"2015-","publisher":"Taylor & Francis ; Landes Bioscience","publisherPlace":"London ; Austin, Tex.","dateIssuedKey":"2015"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["516805320"],"issn":["1559-2308"],"zdb":["2248598-3"]},"title":[{"title":"Epigenetics","subtitle":"the official journal of the DNA Methylation Society","title_sort":"Epigenetics"}],"recId":"516805320"}],"origin":[{"dateIssuedKey":"2018","dateIssuedDisp":"2018, May 3"}],"name":{"displayForm":["Hagen Klett, Yesilda Balavarca, Reka Toth, Biljana Gigic, Nina Habermann, Dominique Scherer, Petra Schrotz-King, Alexis Ulrich, Peter Schirmacher, Esther Herpel, Hermann Brenner, Cornelia M. Ulrich, Karin B. Michels, Hauke Busch and Melanie Boerries"]},"language":["eng"],"person":[{"family":"Klett","role":"aut","display":"Klett, Hagen","given":"Hagen"},{"role":"aut","family":"Balavarca","given":"Yesilda","display":"Balavarca, Yesilda"},{"role":"aut","family":"Toth","given":"Reka","display":"Toth, Reka"},{"family":"Gigić","role":"aut","given":"Biljana","display":"Gigić, Biljana"},{"role":"aut","family":"Habermann","given":"Nina","display":"Habermann, Nina"},{"family":"Scherer","role":"aut","given":"Dominique","display":"Scherer, Dominique"},{"family":"Schrotz-King","role":"aut","given":"Petra","display":"Schrotz-King, Petra"},{"family":"Ulrich","role":"aut","given":"Alexis","display":"Ulrich, Alexis"},{"display":"Schirmacher, Peter","given":"Peter","family":"Schirmacher","role":"aut"},{"family":"Herpel","role":"aut","display":"Herpel, Esther","given":"Esther"},{"role":"aut","family":"Brenner","given":"Hermann","display":"Brenner, Hermann"},{"given":"Cornelia","display":"Ulrich, Cornelia","role":"aut","family":"Ulrich"}],"recId":"1583626352","note":["Gesehen am 12.11.2018"]} | ||
| SRT | |a KLETTHAGENROBUSTPRED2018 | ||