Redefining CpG islands using hidden Markov models

Abstract

The DNA of most vertebrates is depleted in CpG dinucleotide: a C followed by a G in the 5' to 3' direction. CpGs are the target for DNA methylation, a chemical modification of cytosine (C) heritable during cell division and the most well-characterized epigenetic mechanism. The remaining CpGs tend to cluster in regions referred to as CpG islands (CGI). Knowing CGI locations is important because they mark functionally relevant epigenetic loci in development and disease. For various mammals, including human, a readily available and widely used list of CGI is available from the UCSC Genome Browser. This list was derived using algorithms that search for regions satisfying a definition of CGI proposed by Gardiner-Garden and Frommer more than 20 years ago. Recent findings, enabled by advances in technology that permit direct measurement of epigenetic endpoints at a whole-genome scale, motivate the need to adapt the current CGI definition. In this paper, we propose a procedure, guided by hidden Markov models, that permits an extensible approach to detecting CGI. The main advantage of our approach over others is that it summarizes the evidence for CGI status as probability scores. This provides flexibility in the definition of a CGI and facilitates the creation of CGI lists for other species. The utility of this approach is demonstrated by generating the first CGI lists for invertebrates, and the fact that we can create CGI lists that substantially increases overlap with recently discovered epigenetic marks. A CGI list and the probability scores, as a function of genome location, for each species are available at http://www.rafalab.org.

Genome-wide analysis of CpG islands in some livestock genomes and their relationship with genomic features

“…DNA methylation is a type of chemical modification of DNA that can be inherited without changing the backbone of DNA sequence. It involves the addition of a methyl group to DNA, typically occurring at CpG dinucleotide, which can affect gene regulation (Irizarry et al 2009;Wu et al 2010;Jia et al 2016). The DNA of most vertebrates, especially doi: 10.17221/78/2015-CJAS mammals, is depleted in CpG dinucleotides.…”

“…The remaining CpGs clustering in DNA regions are generally referred to as CpG islands (CGIs). There has been growing interest in CGI because they are enriched with the promoters of genes (Hackenberg et al 2010) and by altering DNA methylation in CGIs, they play important roles in the regulation of gene expression and gene silencing in biological processes such as X-chromosome inactivation, imprinting, silencing of intragenomic parasites (Su et al 2010) and considerably, they might help discover the epigenetic causes of cancer (Han and Zhao 2009;Wu et al 2010;Koh et al 2016). Because of their crucial roles, multiple algorithms(either specific species or general purpose) have been developed to identify CGIs in the genomes.…”

A Comprehensive Review of Emerging Computational Methods for Gene Identification

“…In CGIs, some unrevealed principles may play a critical role in transcription regulation [179] and forming an evolutionary force [177]. The redefinition of a CGI [180] and its identification [181] may contribute to gene finding and the studies on CGI and methylation may establish a direct link between epigenetic analysis and genomic studies.…”

Algorithms for CpG Islands Search: New Advantages and Old Problems

“…Taking into consideration all facts mentioned above, it's obviously too early to exclude Aluand similar repeats out of attention speaking on CGIs functionality. Most of the authors (Takai & Jones, 2002;H. Wu et al, 2010) try to build an algorithm for CGI search that avoid CGIs around Alu-repeats.…”

“…As a negative set Alu-repeats are usually used. SWM with higher thresholds for length, GC content and Obs/Exp CpG (Takai & Jones, 2003;) and clustering algorithms (Glass et al, 2007;Hackenberg et al, 2010a;H. Wu et al, 2010) show best results.…”