Siphy (SIte-specific PHYlogenetic analysis) analyzes multiple sequence alignments and single outs bases or small regions that are undergoing selection by looking at reduction in substitution rates and unexpected detecting substitution patterns. A specific program to detect conserved transcription factor binding sites is also available.
The Broad Institute, Cambridge, MA
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Manuel Garber et al.
Identifying novel constrained elements by exploiting biased substitution patterns,
Bioinformatics 2009 25(12):i54-i62.