Dataset Information

Statistical power of phylo-HMM for evolutionarily conserved element detection.

ABSTRACT:

Background

An important goal of comparative genomics is the identification of functional elements through conservation analysis. Phylo-HMM was recently introduced to detect conserved elements based on multiple genome alignments, but the method has not been rigorously evaluated.

Results

We report here a simulation study to investigate the power of phylo-HMM. We show that the power of the phylo-HMM approach depends on many factors, the most important being the number of species-specific genomes used and evolutionary distances between pairs of species. This finding is consistent with results reported by other groups for simpler comparative genomics models. In addition, the conservation ratio of conserved elements and the expected length of the conserved elements are also major factors. In contrast, the influence of the topology and the nucleotide substitution model are relatively minor factors.

Conclusion

Our results provide for general guidelines on how to select the number of genomes and their evolutionary distance in comparative genomics studies, as well as the level of power we can expect under different parameter settings.

SUBMITTER: Fan X

PROVIDER: S-EPMC2194792 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Publications

Statistical power of phylo-HMM for evolutionarily conserved element detection.

Fan Xiaodan X Zhu Jun J Schadt Eric E EE Liu Jun S JS

BMC bioinformatics 20071005

<h4>Background</h4>An important goal of comparative genomics is the identification of functional elements through conservation analysis. Phylo-HMM was recently introduced to detect conserved elements based on multiple genome alignments, but the method has not been rigorously evaluated.<h4>Results</h4>We report here a simulation study to investigate the power of phylo-HMM. We show that the power of the phylo-HMM approach depends on many factors, the most important being the number of species-spec ...[more]

PMID: 17919331

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Project description:Zebrafish (Danio rerio) is an excellent model organism for the study of vertebrate development including skeletogenesis. Studies of mammalian cartilage formation were greatly advanced through the use of a cartilage specific regulatory element of the Collagen type II alpha 1 (Col2a1) gene. In an effort to isolate such an element in zebrafish, we compared the expression of two col2a1 homologues and found that expression of col2a1b, a previously uncharacterized zebrafish homologue, only partially overlaps with col2a1a. We focused our analysis on col2a1a, as it is expressed in both the stacked chondrocytes and the perichondrium. By comparing the genomic sequence surrounding the predicted transcriptional start site of col2a1a among several species of teleosts we identified a small highly conserved sequence (R2) located 1.7 kb upstream of the presumptive transcriptional initiation site. Interestingly, neither the sequence nor location of this element is conserved between teleost and mammalian Col2a1. We generated transient and stable transgenic lines with just the R2 element or the entire 1.7 kb fragment 5' of the transcriptional initiation site. The identified regulatory elements enable the tracking of cellular development in various tissues by driving robust reporter expression in craniofacial cartilage, ear, notochord, floor plate, hypochord and fins in a pattern similar to the expression of endogenous col2a1a. Using a reporter gene driven by the R2 regulatory element, we analyzed the morphogenesis of the notochord sheath cells as they withdraw from the stack of initially uniform cells and encase the inflating vacuolated notochord cells. Finally, we show that like endogenous col2a1a, craniofacial expression of these reporter constructs depends on Sox9a transcription factor activity. At the same time, notochord expression is maintained after Sox9a knockdown, suggesting that other factors can activate expression through the identified regulatory element in this tissue.

Dataset Information

Statistical power of phylo-HMM for evolutionarily conserved element detection.

Background

Results

Conclusion

Publications

Statistical power of phylo-HMM for evolutionarily conserved element detection.

Similar Datasets

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