Identifying protein-binding sites from unaligned DNA fragments.
The ability to determine important features within DNA sequences from the sequences alone is becoming essential as large-scale sequencing projects are being undertaken. We present a method that can be applied to the problem of identifying the recognition pattern for a DNA-binding protein given only a collection of sequenced DNA fragments, each known to contain somewhere within it a binding site for that protein. Information about the position or orientation of the binding sites within those fragments is not needed. The method compares the "information content" of a large number of possible binding site alignments to arrive at a matrix representation of the binding site pattern. The specificity of the protein is represented as a matrix, rather than a consensus sequence, allowing patterns that are typical of regulatory protein-binding sites to be identified. The reliability of the method improves as the number of sequences increases, but the time required increases only linearly with the number of sequences. An example, using known cAMP receptor protein-binding sites, illustrates the method.
Stormo
G D
GD
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309.
Hartzell
G W
GW
D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein; D004247:DNA / Q000378:metabolism*; D007256:Information Systems; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D009363:Neoplasm Proteins; D011506:Proteins; D004247:DNA