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Computational methods to detect conserved non-genic elements in phylogenetically isolated genomes: application to
Michael Hiller1, Saatvik Agarwal, James H Notwell
1Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA, Department of Computer Science, Stanford University, Stanford, CA 94305, USA and Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
Nucleic Acids Research
|July 2, 2013
Summary
This study introduces a new comparative genomics framework to align isolated genomes, enabling better detection of conserved non-genic elements (CNEs). The method significantly improves CNE discovery in zebrafish, aiding evolutionary and biomedical research.
Area of Science:
- Comparative genomics
- Evolutionary biology
- Bioinformatics
Background:
- Many model organisms have isolated genomes, hindering comparative genomic analysis.
- Phylogenetic isolation, like in zebrafish, complicates genome alignment and the identification of conserved non-genic elements (CNEs).
- Detecting CNEs is crucial for understanding cis-regulatory elements with biological importance.
Purpose of the Study:
- To develop a general comparative genomics framework for aligning isolated genomes.
- To comprehensively detect conserved non-genic elements (CNEs) in phylogenetically distant species.
- To improve CNE detection and quality in zebrafish.
Main Methods:
- Integration of sensitive, quality-controlled local alignments.
- Utilizing alignment transitivity and ancestral reconstruction to bridge large evolutionary distances.
- Application of the framework to zebrafish genome alignment and CNE detection.
Main Results:
- A novel framework for aligning isolated genomes and detecting CNEs was developed.
- Substantially improved CNE detection and quality in zebrafish compared to previous methods.
- Identified 54,533 zebrafish CNEs, with 22% conserved in human or mouse, enriched in known enhancers.
Conclusions:
- The developed framework effectively addresses challenges in aligning isolated genomes.
- The new zebrafish CNE set provides valuable resources for cis-regulation, development, and disease research.
- The framework is applicable to other isolated genomes like frog, amphioxus, and C. elegans.
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