Combinatorial Identification of DNA Methylation Patterns over Age in the Human Brain

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2016 Sep 25

PMID 27663458

Citations 6

Authors

Behrooz Torabi Moghadam

Michal Dabrowski

Bozena Kaminska

Manfred G Grabherr

Jan Komorowski

Affiliations

Soon will be listed here.

Abstract

Background: DNA methylation plays a key role in developmental processes, which is reflected in changing methylation patterns at specific CpG sites over the lifetime of an individual. The underlying mechanisms are complex and possibly affect multiple genes or entire pathways.

Results: We applied a multivariate approach to identify combinations of CpG sites that undergo modifications when transitioning between developmental stages. Monte Carlo feature selection produced a list of ranked and statistically significant CpG sites, while rule-based models allowed for identifying particular methylation changes in these sites. Our rule-based classifier reports combinations of CpG sites, together with changes in their methylation status in the form of easy-to-read IF-THEN rules, which allows for identification of the genes associated with the underlying sites.

Conclusion: We utilized machine learning and statistical methods to discretize decision class (age) values to get a general pattern of methylation changes over the lifespan. The CpG sites present in the significant rules were annotated to genes involved in brain formation, general development, as well as genes linked to cancer and Alzheimer's disease.

Citing Articles

Epigenetic disruptions in the offspring hypothalamus in response to maternal infection.

Alsegehy S, Southey B, Hernandez A, Rund L, Antonson A, Nowak R Gene. 2024; 910:148329.

PMID: 38431234 PMC: 11826927. DOI: 10.1016/j.gene.2024.148329.

Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer.

Dong D, Zhang R, Shao J, Zhang A, Wang Y, Zhou Y Clin Epigenetics. 2021; 13(1):225.

PMID: 34922605 PMC: 8684698. DOI: 10.1186/s13148-021-01211-5.

Determination of epigenetic age through DNA methylation of NPTX2 gene using buccal scrapes: A pilot study.

Khan N, Bavle R, Makarla S, Konda P, Amulya S, Hosthor S J Forensic Dent Sci. 2020; 11(3):147-152.

PMID: 32801587 PMC: 7398359. DOI: 10.4103/jfo.jfds_29_19.

Genome-wide prediction and prioritization of human aging genes by data fusion: a machine learning approach.

Arabfard M, Ohadi M, Rezaei Tabar V, Delbari A, Kavousi K BMC Genomics. 2019; 20(1):832.

PMID: 31706268 PMC: 6842548. DOI: 10.1186/s12864-019-6140-0.

Analyzing DNA methylation patterns in subjects diagnosed with schizophrenia using machine learning methods.

Moghadam B, Etemadikhah M, Rajkowska G, Stockmeier C, Grabherr M, Komorowski J J Psychiatr Res. 2019; 114:41-47.

PMID: 31022588 PMC: 7416578. DOI: 10.1016/j.jpsychires.2019.04.001.

References

Bocklandt S, Lin W, Sehl M, Sanchez F, Sinsheimer J, Horvath S . Epigenetic predictor of age. PLoS One. 2011; 6(6):e14821. PMC: 3120753. DOI: 10.1371/journal.pone.0014821. View

Tomasini R, Tsuchihara K, Wilhelm M, Fujitani M, Rufini A, Cheung C . TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev. 2008; 22(19):2677-91. PMC: 2559903. DOI: 10.1101/gad.1695308. View

Zhang B, Zhou Y, Lin N, Lowdon R, Hong C, Nagarajan R . Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm. Genome Res. 2013; 23(9):1522-40. PMC: 3759728. DOI: 10.1101/gr.156539.113. View

Robertson K . DNA methylation and human disease. Nat Rev Genet. 2005; 6(8):597-610. DOI: 10.1038/nrg1655. View

Silva D, Antunes J, Balamurugan K, Duncan G, Alho C, McCord B . Evaluation of DNA methylation markers and their potential to predict human aging. Electrophoresis. 2015; 36(15):1775-80. DOI: 10.1002/elps.201500137. View

Bekku Y, Vargova L, Goto Y, Vorisek I, Dmytrenko L, Narasaki M . Bral1: its role in diffusion barrier formation and conduction velocity in the CNS. J Neurosci. 2010; 30(8):3113-23. PMC: 6633924. DOI: 10.1523/JNEUROSCI.5598-09.2010. View

Zhang G, Pradhan S . Mammalian epigenetic mechanisms. IUBMB Life. 2014; 66(4):240-56. DOI: 10.1002/iub.1264. View

Bhate A, Parker D, Bebee T, Ahn J, Arif W, Rashan E . ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation. Nat Commun. 2015; 6:8768. PMC: 4635967. DOI: 10.1038/ncomms9768. View

Appelbaum L, Wang G, Yokogawa T, Skariah G, Smith S, Mourrain P . Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron. 2010; 68(1):87-98. PMC: 2969179. DOI: 10.1016/j.neuron.2010.09.006. View

10.

Dmytriyeva O, Pankratova S, Owczarek S, Sonn K, Soroka V, Ridley C . The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. Nat Commun. 2012; 3:1197. DOI: 10.1038/ncomms2202. View

11.

Numata S, Ye T, Hyde T, Guitart-Navarro X, Tao R, Wininger M . DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Hum Genet. 2012; 90(2):260-72. PMC: 3276664. DOI: 10.1016/j.ajhg.2011.12.020. View

12.

Horvath S . DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14(10):R115. PMC: 4015143. DOI: 10.1186/gb-2013-14-10-r115. View

13.

Bornelov S, Marillet S, Komorowski J . Ciruvis: a web-based tool for rule networks and interaction detection using rule-based classifiers. BMC Bioinformatics. 2014; 15:139. PMC: 4030460. DOI: 10.1186/1471-2105-15-139. View

14.

Smith Z, Meissner A . DNA methylation: roles in mammalian development. Nat Rev Genet. 2013; 14(3):204-20. DOI: 10.1038/nrg3354. View

15.

Maglott D, Ostell J, Pruitt K, Tatusova T . Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res. 2006; 35(Database issue):D26-31. PMC: 1761442. DOI: 10.1093/nar/gkl993. View

16.

Klose R, Bird A . Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 2006; 31(2):89-97. DOI: 10.1016/j.tibs.2005.12.008. View

17.

Ingeson-Carlsson C, Nilsson M . Switching from MAPK-dependent to MAPK-independent repression of the sodium-iodide symporter in 2D and 3D cultured normal thyroid cells. Mol Cell Endocrinol. 2013; 381(1-2):241-54. DOI: 10.1016/j.mce.2013.08.006. View

18.

Saxonov S, Berg P, Brutlag D . A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006; 103(5):1412-7. PMC: 1345710. DOI: 10.1073/pnas.0510310103. View

19.

Barres R, Zierath J . DNA methylation in metabolic disorders. Am J Clin Nutr. 2011; 93(4):897S-900. DOI: 10.3945/ajcn.110.001933. View

20.

Shukla S, Patric I, Thinagararjan S, Srinivasan S, Mondal B, Hegde A . A DNA methylation prognostic signature of glioblastoma: identification of NPTX2-PTEN-NF-κB nexus. Cancer Res. 2013; 73(22):6563-73. DOI: 10.1158/0008-5472.CAN-13-0298. View