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A Practical Guide to Phylogenetics for Nonexperts
Published on: February 6, 2014
Phylogenetic motif detection by expectation-maximization on evolutionary mixtures
A M Moses1, D Y Chiang, M B Eisen
1Graduate Group in Biophysics, Center for Integrative Genomics, University of California, Berkeley, USA. amoses@ocf.berkeley.edu
Summary
Discovering transcription factor binding sites is enhanced by using evolutionary information from related species. Our new framework improves motif discovery by incorporating phylogenetic data, reducing false positives and identifying important regulatory elements.
Area of Science:
- Computational Biology
- Bioinformatics
- Genomics
Background:
- Transcription factor binding sites (TFBS) are crucial regulatory elements in DNA.
- Conserved non-coding sequences across species offer valuable insights for TFBS identification.
- Existing motif discovery tools often do not fully leverage evolutionary information.
Purpose of the Study:
- To develop a unified probabilistic framework for motif discovery that integrates evolutionary information.
- To improve the accuracy and efficiency of identifying transcription factor binding sites.
- To leverage phylogenetic data for more robust motif discovery.
Main Methods:
- Developed a probabilistic framework treating aligned DNA sequences as a mixture of evolutionary models (motif and background).
- Employed the Expectation-Maximization algorithm for parameter estimation, inspired by the MEME program.
- Incorporated various evolutionary models and phylogenetic information into the motif discovery process.
Main Results:
- Demonstrated that the proposed approach effectively utilizes phylogenetic information to enhance motif discovery.
- Showed a reduction in false positives compared to traditional methods relying solely on conserved regions.
- Successfully identified motifs upstream of groups of characterized target genes.
Conclusions:
- Integrating evolutionary information into motif discovery significantly improves accuracy and reduces false positives.
- The developed framework offers a powerful tool for identifying functional regulatory elements in non-coding DNA.
- Phylogenetic analysis is a key component for advancing motif discovery in comparative genomics.
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