Dataset Information

Identification of CpG islands in DNA sequences using statistically optimal null filters.

ABSTRACT: : CpG dinucleotide clusters also referred to as CpG islands (CGIs) are usually located in the promoter regions of genes in a deoxyribonucleic acid (DNA) sequence. CGIs play a crucial role in gene expression and cell differentiation, as such, they are normally used as gene markers. The earlier CGI identification methods used the rich CpG dinucleotide content in CGIs, as a characteristic measure to identify the locations of CGIs. The fact, that the probability of nucleotide G following nucleotide C in a CGI is greater as compared to a non-CGI, is employed by some of the recent methods. These methods use the difference in transition probabilities between subsequent nucleotides to distinguish between a CGI from a non-CGI. These transition probabilities vary with the data being analyzed and several of them have been reported in the literature sometimes leading to contradictory results. In this article, we propose a new and efficient scheme for identification of CGIs using statistically optimal null filters. We formulate a new CGI identification characteristic to reliably and efficiently identify CGIs in a given DNA sequence which is devoid of any ambiguities. Our proposed scheme combines maximum signal-to-noise ratio and least squares optimization criteria to estimate the CGI identification characteristic in the DNA sequence. The proposed scheme is tested on a number of DNA sequences taken from human chromosomes 21 and 22, and proved to be highly reliable as well as efficient in identifying the CGIs.

SUBMITTER: Kakumani R

PROVIDER: S-EPMC3570435 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Identification of CpG islands in DNA sequences using statistically optimal null filters.

Kakumani Rajasekhar R Ahmad Omair O Devabhaktuni Vijay V

EURASIP journal on bioinformatics & systems biology 20120829 1

: CpG dinucleotide clusters also referred to as CpG islands (CGIs) are usually located in the promoter regions of genes in a deoxyribonucleic acid (DNA) sequence. CGIs play a crucial role in gene expression and cell differentiation, as such, they are normally used as gene markers. The earlier CGI identification methods used the rich CpG dinucleotide content in CGIs, as a characteristic measure to identify the locations of CGIs. The fact, that the probability of nucleotide G following nucleotide ...[more]

PMID: 22931396

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Project description:BackgroundMammalian CpG islands (CGIs) normally escape DNA methylation in all adult tissues and developmental stages. However, in our previous study we unexpectedly identified many methylated CGIs in human peripheral blood leukocytes. Methylated CpG dinucleotides convert to TpG dinucleotides through deaminization of their cytosine bases more frequently than hypomethylated CpG dinucleotides. Therefore, we wondered how methylated CGIs in germline or non-germline cells maintain their CpG-rich sequences. It is known that events such as germline hypomethylation, CpG selection, biased gene conversion (BGC), and frequent CpG fixation can contribute to the maintenance of CpG-rich sequences in methylated CGIs in germline or non-germline cells. However, it has not been investigated which of the processes maintain CpG-rich sequences of methylated CGIs in each genomic position.ResultsIn this study, we comprehensively examined the contribution of the processes described above to the maintenance of CpG-rich sequences in methylated CGIs in germline and non-germline cells which were classified by genomic positions. Approximately 60-80% of CGIs with high methylation in H1 cell line (H1-HM) in all the genomic positions showed a low average CpG→TpG/CpA substitution rate. In contrast, fewer than half the numbers of CGIs with H1-HM in all the genomic positions showed a low average CpG→TpG/CpA substitution rate and low levels of methylation in sperm cells (SPM-LM). Furthermore, a small fraction of CGIs with a low average CpG→TpG/CpA substitution rate and high levels of methylation in sperm cells (SPM-HM) showed CpG selection. On the other hand, independent of the positions in genes, most CGIs with SPM-HM showed a slightly higher average TpG/CpA→CpG substitution rate compared with those with SPM-LM.ConclusionsRelatively high numbers (approximately 60-80%) of CGIs with H1-HM in all the genomic positions preserve their CpG-rich sequences by a low CpG→TpG/CpA substitution rate caused mainly by their SPM-LM, and for those with SPM-HM partly by CpG selection and TpG/CpA→CpG fixation. BGC has little contribution to the maintenance of CpG-rich sequences of CGIs with SPM-HM which were classified by genomic positions.

Dataset Information

Identification of CpG islands in DNA sequences using statistically optimal null filters.

Publications

Identification of CpG islands in DNA sequences using statistically optimal null filters.

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