Cross-cell DNA methylation annotation and analysis for pan-cancer study
DOI:
https://doi.org/10.3329/bjp.v11iS1.26851Keywords:
DNA methylation, Pan-cancerAbstract
Pan-cancer study can uncover cell- and tissue-specific genomic loci and regions with underlying biological functions, as one of fundamental procedures toward precision medicine. We utilized the online curated resource of DNA methylation annotation knowledgebase, to implement the cross-cell interrogation of pan-cancer study of breast cancer. The study revealed genome-wide differentially-methylated loci and regions by the reduced representation bisulfite sequencing profiling. The knowledgebase contains three level of curated information across multiple cancer and normal cells from the ENCODE Consortium. The reference base covers all identified differentially-methylation CpG sites and regions of interest, further annotated gene information, together with tumor suppressor gene and methylation level. Lastly, it includes the inferred functional association network and related Gene Ontology analysis results based on all the tumor suppressor genes identified from the differentially-methylated regions of interest. Our knowledgebase and analysis results provide a thorough reference source for biomedical researchers and clinicians. The cross-cell analysis results are deposited at: http://github.com/gladex/DMAK.
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Akalin A, Garrett-Bakelman FE, Kormaksson M, Busuttil J, Zhang L, Khrebtukova I, Milne TA, Huang Y, Biswas D, Hess JL, Allis CD, Roeder RG, Valk PJM, Löwenberg B, Delwel R, Fernandez HF, Paietta E, Tallman MS, Schroth GP, Mason CE, Melnick A, Figueroa ME. Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet 2012a; 8: e1002781.
Akalin A, Kormaksson M, Li S, Garrett-Bakelman F, Figueroa M, Melnick A, Mason C. Methylkit. A comprehensive r package for the analysis of genome-wide DNA methylation profiles. Genome Biology 2012b; 13: R87.
Bedi U, Mishra VK, Wasilewski D, Scheel C, Johnsen SA. Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer. Oncotarget 2014; 5: 2016-29.
Blattler A, Yao L, Witt H, Guo Y, Nicolet C, Berman B, Farnham P. Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes. Genome Biology 2014; 15: 469.
Bock C, Lengauer T: Computational epigenetics. Bioinformatics 2008; 24: 1-10.
de Souza N. Genomics: The encode project. Nat Meth 2012; 9: 1046-1046.
Kemp Christopher J, Moore James M, Moser R, Bernard B, Teater M, Smith Leslie E, Rabaia Natalia A, Gurley Kay E, Guinney J, Busch Stephanie E, Shaknovich R, Lobanenkov Victor V, Liggitt D, Shmulevich I, Melnick A, Filippova Galina N. Ctcf haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Reports 2014; 7: 1020-29.
Kristensen VN, Lingjaerde OC, Russnes HG, Vollan HKM, Frigessi A, Borresen-Dale A-L. Principles and methods of integrative genomic analyses in cancer. Nat Rev Cancer 2014; 14: 299-313.
Leiserson MDM, Vandin F, Wu H-T, Dobson JR, Eldridge JV, Thomas JL, Papoutsaki A, Kim Y, Niu B, McLellan M, Lawrence MS, Gonzalez-Perez A, Tamborero D, Cheng Y, Ryslik GA, Lopez-Bigas N, Getz G, Ding L, Raphael BJ. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet 2015; 47: 106-14.
Pennisi E. Encode project writes eulogy for junk DNA. Sci 2012; 337: 1159-61.
Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu Y-C, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh K-H, Feizi S, Karlic R, Kim A-R, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJM, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai L-H, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Roadmap Epigenomics C: Integrative analysis of 111 reference human epigenomes. Nature 2015; 518: 317-30.
Sherman B, Huang D, Tan Q, Guo Y, Bour S, Liu D, Stephens R, Baseler M, Lane HC, Lempicki R. David knowledgebase: A gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics. 2007; 8: 426.
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. String v10: Proteinprotein interaction networks, integrated over the tree of life. Nucleic Acids Research 2015; 43: D447-52.
Tang B, Wang X. Inferring genome-wide interplay landscape between DNA methylation and transcriptional regulation P J Pharm Sci 2015; 28: 349-52.
The Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The cancer genome atlas pan-cancer analysis project. Nat Genet 2013; 45: 1113-20.
The ENCODE Project Consortium: An integrated encyclopedia of DNA elements in the human genome. Nature 2012; 489: 57-74.
Witte T, Plass C, Gerhauser C. Pan-cancer patterns of DNA methylation. Genome Med. 2014; 6: 1-18.
Zhao M, Sun J, Zhao Z: Tsgene. A web resource for tumor suppressor genes. Nucleic Acids Research 2013; 41: D970-76.
Ziller MJ, Gu H, Muller F, Donaghey J, Tsai LTY, Kohlbacher O, De Jager PL, Rosen ED, Bennett DA, Bernstein BE, Gnirke A, Meissner A. Charting a dynamic DNA methylation landscape of the human genome. Nature 2013; 500: 477-81.
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