Supplementary Tables

BioProspector Search

About the Authors

Comparative genomics is a promising approach to the challenging problem of eukaryotic transcription regulatory element identification, since functional non-coding sequences may be conserved across species due to evolutionary constraints. We systematically analyzed known human and S. cerevisiae transcription regulatory elements and discovered that known human regulatory elements are more conserved between human and mouse than background sequences. Though known S. cerevisiae regulatory elements do not appear to be more conserved by comparison of S. cerevisiae to S. pombe, they are more conserved when compared to multiple other yeast genomes (S. paradoxus, S. mikatae, and S. bayanus) using multiple sequence alignment.

Based on these analyses, we developed a sequence motif-finding algorithm called CompareProspector, which extends Gibbs sampling by biasing the search in promoter regions conserved across species. Using human–mouse comparison, CompareProspector correctly identified the known motifs for transcription factors Mef2, Myf, Srf, and Sp1 from a set of human muscle-specific genes. It also discovered the NFAT motif from genes upregulated by CD28 stimulation in T cells, which suggests the direct involvement of NFAT in mediating CD28 stimulatory signal. Using C. elegans–C. briggsae comparison, CompareProspector found the PHA-4 motif from pharyngeally expressed genes and the UNC-86 motif from genes known to be regulated by UNC-86. CompareProspector outperformed many other computational motif-finding programs tested, demonstrating the power of comparative genomics-based biased sampling in eukaryotic regulatory element identification.

CompareProspector paper in Genome Research


Last updated: 1/3/2004

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