CpGProD: identifying CpG islands associated with transcription
  start sites in large genomic mammalian sequences

Ponger, Loïc; Mouchiroud, Dominique

doi:10.1093/bioinformatics/18.4.631

Cited by 165 publications

(99 citation statements)

References 14 publications

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“…The fundamental advance of our analysis was to move beyond a purely sequence-based definition of CpG islands (which many researchers have tried to optimize in the past [29][30][31][32][33]) and to incorporate epigenome and chromatin data. This approach is consistent with the common notion of CpG islands being functionally and epigenetically exceptional regions, but gave rise to two conceptual difficulties.…”

Section: Discussionmentioning

confidence: 99%

CpG island mapping by epigenome prediction

Bock¹,

Walter²,

Paulsen³

et al. 2005

PLoS Comput Biol

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CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1) reliance on arbitrary threshold parameters that bear little biological justification, (2) failure to account for widespread heterogeneity among CpG islands, and (3) apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of ''CpG island strength'' that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strength for each CpG island in the human genome, i.e., its inherent tendency to exhibit an open and transcriptionally competent chromatin structure. We extensively validate our results on independent datasets, showing that the CpG island strength predictions are applicable and informative across different tissues and cell types, and we derive improved maps of predicted ''bona fide'' CpG islands. The mapping of CpG islands by epigenome prediction is conceptually superior to identifying CpG islands by widely used sequence criteria since it links CpG island detection to their characteristic epigenetic and functional states. And it is superior to purely experimental epigenome mapping for CpG island detection since it abstracts from specific properties that are limited to a single cell type or tissue. In addition, using computational epigenetics methods we could identify high correlation between the epigenome and characteristics of the DNA sequence, a finding which emphasizes the need for a better understanding of the mechanistic links between genome and epigenome.

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Section: Discussionmentioning

confidence: 99%

CpG island mapping by epigenome prediction

Bock¹,

Walter²,

Paulsen³

et al. 2005

PLoS Comput Biol

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“…Promoter analysis and DNA amplification Prediction of promoters associated with CpG islands were done with CpGProD (Ponger and Mouchiroud, 2002) and CpG islands were also searched with CpG island searcher (URL: http://cpgislands.usc. edu).…”

Section: Confirmation Of Methylation Statusmentioning

confidence: 99%

Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours

et al. 2007

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Chromosome 1p is frequently deleted in neuroblastoma (NB) tumours. The commonly deleted region has been narrowed down by loss of heterozygosity studies undertaken by different groups. Based on earlier mapping data, we have focused on a region on 1p36 (chr1: 7 765 595 -11 019 814) and performed an analysis of 30 genes by exploring features such as epigenetic regulation, that is DNA methylation and histone deacetylation, mutations at the DNA level and mRNA expression. Treatment of NB cell lines with the histone deacetylase inhibitor trichostatin A led to increased gene transcription of four of the 30 genes, ERRFI1 (MIG-6), PIK3CD, RBP7 (CRBPIV) and CASZ1, indicating that these genes could be affected by epigenetic downregulation in NBs. Two patients with nonsynonymous mutations in the PIK3CD gene were detected. One patient harboured three variations in the same exon, and p.R188W. The other patient had the variation p.M655I. In addition, synonymous variations and one variation in an intronic sequence were also found. The mRNA expression of this gene is downregulated in unfavourable, compared to favourable, NBs. One nonsynonymous mutation was also identified in the ERRFI1 gene, p.N343S, and one synonymous. None of the variations above were found in healthy control individuals. In conclusion, of the 30 genes analysed, the PIK3CD gene stands out as one of the most interesting for further studies of NB development and progression.

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“…Furthermore, it extends 5 kb upstream from the most proximal transcript (variant 2). The following programs were used for predictions of promoter locations and CpG-islands: CpG-promoter (http://rulai.cshl.org/tools/CpG_pro-moter/) (Ioshikhes and Zhang 2000), FirstEF (http:// rulai.cshl.org/tools/FirstEF/) (Davuluri et al 2001), and CpGProD (http://pbil.univ-lyon1.fr/software/cpgprod_query.html) (Ponger and Mouchiroud 2002). If masking of repeats was deemed necessary (Bajic et al 2004), the RepeatMasker webserver was used (http:// www.repeatmasker.org/).…”

Section: Patientsmentioning

confidence: 99%

Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

et al. 2005

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Sotos syndrome (SoS, OMIM#117550) is an overgrowth disorder characterized by excessive growth-especially in the first years of childhood-distinctive craniofacial features, and various degrees of mental retardation. Haploinsufficiency of the nuclear receptor binding SET domain containing protein 1 (NSD1) gene, due to either intragenic mutations or whole-gene microdeletions, is found in the majority of patients with SoS. However, in approximately 10-40% of patients with a typical SoS phenotype, no abnormalities are detected. In this study, hemizygous hypermethylation or genomic sequence abnormalities of the promoter region of NSD1 were hypothesized to be the underlying cause in patients with a SoS phenotype, but without confirmed NSD1 alterations. In 18 patients, including one patient with a reported hepatocellular carcinoma, the promoter region of NSD1 was analyzed.However, no hypermethylation or sequence abnormalities in the promoter region could be detected. It therefore seems unlikely that such abnormalities of NSD1 are a major culprit in patients with phenotypical SoS. Additional methods are necessary for detection of other genetic or epigenetic causes of SoS.

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CpGProD: identifying CpG islands associated with transcription start sites in large genomic mammalian sequences

Abstract: http://pbil.univ-lyon1.fr/software/cpgprod.html

Cited by 165 publications

References 14 publications

CpG island mapping by epigenome prediction

CpG island mapping by epigenome prediction

Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours

Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype

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