Computational epigenetics
Encyclopedia
Computational epigenetics
uses bioinformatic methods to complement experimental research in epigenetics
. Due to the recent explosion of epigenome datasets, computational methods play an increasing role in all areas of epigenetic research.
, ChIP-seq and bisulfite sequencing
. All of these methods generate large amounts of data and require efficient ways of data processing and quality control by bioinformatic methods.
of epigenetic information from characteristics of the genome sequence. Such predictions serve a dual purpose. First, accurate epigenome predictions can substitute for experimental data, to some degree, which is particularly relevant for newly discovered epigenetic mechanisms and for species other than human and mouse. Second, prediction algorithms build statistical models of epigenetic information from training data and can therefore act as a first step toward quantitative modeling of an epigenetic mechanism.
opens up new opportunities for improved diagnosis and therapy. These active areas of research give rise to two questions that are particularly amenable to bioinformatic analysis. First, given a list of genomic regions exhibiting epigenetic differences between tumor cells and controls (or between different disease subtypes), can we detect common patterns or find evidence of a functional relationship of these regions to cancer? Second, can we use bioinformatic methods in order to improve diagnosis and therapy by detecting and classifying important disease subtypes?
uses bioinformatic methods to complement experimental research in epigenetics
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
. Due to the recent explosion of epigenome datasets, computational methods play an increasing role in all areas of epigenetic research.
Definition
Research in computational epigenetics comprises the development and application of bioinformatic methods for solving epigenetic questions, as well as computational data analysis and theoretical modeling in the context of epigenetics.Epigenetic data processing and analysis
Various experimental techniques have been developed for genome-wide mapping of epigenetic information, the most widely used being ChIP-on-chipChIP-on-chip
ChIP-on-chip is a technique that combines chromatin immunoprecipitation with microarray technology . Like regular ChIP, ChIP-on-chip is used to investigate interactions between proteins and DNA in vivo...
, ChIP-seq and bisulfite sequencing
Bisulfite sequencing
Bisulfite sequencing is the use of bisulfite treatment of DNA to determine its pattern of methylation. DNA methylation was the first discovered epigenetic mark, and remains the most studied...
. All of these methods generate large amounts of data and require efficient ways of data processing and quality control by bioinformatic methods.
Epigenome prediction
A substantial amount of bioinformatic research has been devoted to the predictionPrediction
A prediction or forecast is a statement about the way things will happen in the future, often but not always based on experience or knowledge...
of epigenetic information from characteristics of the genome sequence. Such predictions serve a dual purpose. First, accurate epigenome predictions can substitute for experimental data, to some degree, which is particularly relevant for newly discovered epigenetic mechanisms and for species other than human and mouse. Second, prediction algorithms build statistical models of epigenetic information from training data and can therefore act as a first step toward quantitative modeling of an epigenetic mechanism.
Applications in cancer epigenetics
The important role of epigenetic defects for cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
opens up new opportunities for improved diagnosis and therapy. These active areas of research give rise to two questions that are particularly amenable to bioinformatic analysis. First, given a list of genomic regions exhibiting epigenetic differences between tumor cells and controls (or between different disease subtypes), can we detect common patterns or find evidence of a functional relationship of these regions to cancer? Second, can we use bioinformatic methods in order to improve diagnosis and therapy by detecting and classifying important disease subtypes?
Emerging topics
The first wave of research in the field of computational epigenetics was driven by rapid progress of experimental methods for data generation, which required adequate computational methods for data processing and quality control, prompted epigenome prediction studies as a means of understanding the genomic distribution of epigenetic information, and provided the foundation for initial projects on cancer epigenetics. While these topics will continue to be major areas of research and the mere quantity of epigenetic data arising from epigenome projects poses a significant bioinformatic challenge, several additional topics are currently emerging.- Epigenetic regulatory circuitry: Reverse engineering the regulatory networks that read, write and execute epigenetic codes.
- Population epigenetics: Distilling regulatory mechanisms from the integration of epigenome data with gene expressionGene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
profiles and haplotypeHaplotypeA haplotype in genetics is a combination of alleles at adjacent locations on the chromosome that are transmitted together...
maps for a large sample from a heterogeneous population. - Evolutionary epigenetics: Learning about epigenome regulation in human (and its medical consequences) by cross-species comparisons.
- Theoretical modeling: Testing our mechanistic and quantitative understanding of epigenetic mechanisms by in silicoIn silicoIn silico is an expression used to mean "performed on computer or via computer simulation." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo and in vitro which are commonly used in biology and refer to experiments done in living organisms and outside of living organisms,...
simulation. - Genome browsers: Developing a new blend of web services that enable biologists to perform sophisticated genome and epigenome analysis within an easy-to-use genome browser environment.
- Medical epigenetics: Searching for epigenetic mechanisms that play a role in diseases other than cancer, as there is strong circumstantial evidence for epigenetic regulation being involved in mental disorders, autoimmune diseases and other complex diseases.
Epigenetics Databases
- MethDBMethDBMethDB is a database for DNA methylation data....
http://www.methdb.de Contains information on 19,905 DNA methylation content data and 5,382 methylation patterns for 48 species, 1,511 individuals, 198 tissues and cell lines and 79 phenotypes. - PubMethPubmethPubMeth is a database that contains information about DNA hypermethylation in cancer. It can be queried either by searching a list of genes, or cancer types.It was created at the Lab. for bioinformatics and computational genomics...
http://www.pubmeth.org/ Contains over 5,000 records on methylated genes in various cancer types. - REBASERebaseRebase is a village in Kambja Parish, Tartu County in eastern Estonia....
http://rebase.neb.com/rebase/rebase.html Contains over 22,000 DNA methyltransferases genes derived from GenBank. - MeInfoText http://mit.lifescience.ntu.edu.tw/ Contains gene methylation information across 205 human cancer types.
- MethPrimerDB http://medgen.ugent.be/methprimerdb/ Contains 259 primer sets from human, mouse and rat for DNA methylation analysis.
- The Histone Database http://genome.nhgri.nih.gov/histones/ Contains 254 sequences from histone H1, 383 from histone H2, 311 from histone H2B, 1043 from histone H3 and 198 from histone H4, altogether representing at least 857 species.
- ChromDB http://www.chromdb.org/ Contains 9,341 chromatin-associated proteins, including RNAi-associated proteins, for a broad range of organisms.
- CREMOFAC http://www.jncasr.ac.in/cremofac/ Contains 1725 redundant and 720 non-redundant chromatin-remodeling factor sequences in eukaryotes.
- The Krembil Family Epigenetics Laboratory http://www.epigenomics.ca Contains DNA methylation data of human chromosomes 21, 22, male germ cells and DNA methylation profiles in monozygotic and dizygotic twins.
- MethyLogiX DNA methylation database http://www.methylogix.com/genetics/database.shtml.htm Contains DNA methylation data of human chromosomes 21 and 22, male germ cells and late-onset Alzheimer's disease.
- List of epigenetic databases and computational epigenetic tools online (constantly updated)
Sources and further reading
- The original version of this article was based on a review paper on computational epigenetics that appeared in the January 2008 issue of the Bioinformatics journal: Bock, C. and Lengauer, T. (2008) Computational epigenetics. Bioinformatics, 24, 1-10. This review paper provides >100 references to scientific papers and extensive background information. It is published as open access and can be downloaded freely from the publisher’s web page: http://dx.doi.org/10.1093/bioinformatics/btm546.
- Additional data has been updated and added, based on a review paper on computational epigenetics that appeared in the January 2010 issue of the Bioinformation journal: Lim S.J., Tan T.W. and Tong, J.C. (2010) Computational epigenetics: the new scientific paradigm. Bioinformation, 4(7): 331-337. This review paper provides >129 references to scientific papers. It is published as open access and can be downloaded freely from the publisher’s web page: http://bioinformation.net/004/007000042010.pdf.