A novel pairwise comparison method for in silico discovery of statistically significant cis-regulatory elements in eukaryotic promoter regions: Application to Arabidopsis
| Autor: | Mahdi Ebrahimi, Roohollah Shamloo-Dashtpagerdi, Massumeh Aliakbari, Esmaeil Ebrahimie, Hooman Razi, Angelica Lindlöf |
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| Rok vydání: | 2015 |
| Předmět: |
Statistics and Probability
Chromatin Immunoprecipitation In silico Amino Acid Motifs Arabidopsis Context (language use) Regulatory Sequences Nucleic Acid General Biochemistry Genetics and Molecular Biology Gene Expression Regulation Plant Transcriptional regulation Gene Regulatory Networks Poisson Distribution Regulatory Elements Transcriptional Promoter Regions Genetic Gene Probability Genetics Models Statistical General Immunology and Microbiology biology Applied Mathematics Computational Biology Promoter Genomics General Medicine biology.organism_classification Modeling and Simulation Pairwise comparison General Agricultural and Biological Sciences Genome Plant Cis-regulatory element |
| Zdroj: | Journal of Theoretical Biology. 364:364-376 |
| ISSN: | 0022-5193 |
| DOI: | 10.1016/j.jtbi.2014.09.038 |
| Popis: | Cis regulatory elements (CREs), located within promoter regions, play a significant role in the blueprint for transcriptional regulation of genes. There is a growing interest to study the combinatorial nature of CREs including presence or absence of CREs, the number of occurrences of each CRE, as well as of their order and location relative to their target genes. Comparative promoter analysis has been shown to be a reliable strategy to test the significance of each component of promoter architecture. However, it remains unclear what level of difference in the number of occurrences of each CRE is of statistical significance in order to explain different expression patterns of two genes. In this study, we present a novel statistical approach for pairwise comparison of promoters of Arabidopsis genes in the context of number of occurrences of each CRE within the promoters. First, using the sample of 1000 Arabidopsis promoters, the results of the goodness of fit test and non-parametric analysis revealed that the number of occurrences of CREs in a promoter sequence is Poisson distributed. As a promoter sequence contained functional and non-functional CREs, we addressed the issue of the statistical distribution of functional CREs by analyzing the ChIP-seq datasets. The results showed that the number of occurrences of functional CREs over the genomic regions was determined as being Poisson distributed. In accordance with the obtained distribution of CREs occurrences, we suggested the Audic and Claverie (AC) test to compare two promoters based on the number of occurrences for the CREs. Superiority of the AC test over Chi-square (2×2) and Fisher’s exact tests was also shown, as the AC test was able to detect a higher number of significant CREs. The two case studies on the Arabidopsis genes were performed in order to biologically verify the pairwise test for promoter comparison. Consequently, a number of CREs with significantly different occurrences was identified between the promoters. The results of the pairwise comparative analysis together with the expression data for the studied genes revealed the biological significance of the identified CREs. |
| Databáze: | OpenAIRE |
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