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Updated: Jun 30, 2026
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Spotting Cheetahs: Identifying Individuals by Their Footprints
Published on: May 1, 2016
Evaluating phylogenetic footprinting for human-rodent comparisons
Tilman Sauer1, Ekaterina Shelest, Edgar Wingender
1Department of Bioinformatics, UKG, Georg-August-University of Goettingen Goldschmidtstrasse 1, 37077 Goettingen, Germany. tsa@bioinf.med.uni-goettingen.de
Bioinformatics (Oxford, England)
|December 8, 2005
Summary
Phylogenetic footprinting effectively identifies conserved transcription factor binding sites (TFBSs) across species. A 65% sequence identity threshold captures 72% of known TFBSs, though some TFBSs show pattern rather than strict sequence conservation.
Area of Science:
- Genomics
- Bioinformatics
- Evolutionary Biology
Background:
- Phylogenetic footprinting leverages alignments of non-coding orthologous regions to identify regulatory elements and transcription factor binding sites (TFBSs).
- A systematic evaluation is crucial for optimizing its application in discovering novel TFBSs.
Purpose of the Study:
- To systematically evaluate the validity and usability of phylogenetic footprinting for identifying transcription factor binding sites (TFBSs).
- To determine optimal parameters for effective TFBS identification using cross-species comparisons.
Main Methods:
- Utilized 2678 human, mouse, and rat TFBSs from the TRANSFAC database.
- Combined gene annotation and sequence homology searches to ensure orthologous sequence retrieval.
- Evaluated the impact of sequence identity thresholds and alignment algorithms on TFBS identification.
Main Results:
- A sequence identity threshold of at least 65% proved most effective in distinguishing TFBSs from non-functional sequences.
- Approximately 72% of known TFBSs were found to be conserved using this threshold in human-rodent comparisons.
- Conservation levels varied significantly across different transcription factors and depended on the regulated gene's function.
- Some TFBSs exhibited high pattern conservation rather than strict sequence conservation, indicating limitations of purely sequence-based methods.
Conclusions:
- Phylogenetic footprinting, particularly with a 65% sequence identity threshold, is a valuable tool for identifying conserved TFBSs.
- The effectiveness of sequence conservation varies, and pattern conservation should also be considered for a comprehensive analysis.
- This study provides empirical data to refine the application of phylogenetic footprinting in regulatory genomics.
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