Identifying DNA and protein patterns with statistically significant alignments of multiple sequences.
BACKGROUND
Molecular biologists frequently can obtain interesting insight by aligning a set of related DNA, RNA or protein sequences. Such alignments can be used to determine either evolutionary or functional relationships. Our interest is in identifying functional relationships. Unless the sequences are very similar, it is necessary to have a specific strategy for measuring-or scoring-the relatedness of the aligned sequences. If the alignment is not known, one can be determined by finding an alignment that optimizes the scoring scheme.


RESULTS
We describe four components to our approach for determining alignments of multiple sequences. First, we review a log-likelihood scoring scheme we call information content. Second, we describe two methods for estimating the P value of an individual information content score: (i) a method that combines a technique from large-deviation statistics with numerical calculations; (ii) a method that is exclusively numerical. Third, we describe how we count the number of possible alignments given the overall amount of sequence data. This count is multiplied by the P value to determine the expected frequency of an information content score and, thus, the statistical significance of the corresponding alignment. Statistical significance can be used to compare alignments having differing widths and containing differing numbers of sequences. Fourth, we describe a greedy algorithm for determining alignments of functionally related sequences. Finally, we test the accuracy of our P value calculations, and give an example of using our algorithm to identify binding sites for the Escherichia coli CRP protein.


BACKGROUND
Programs were developed under the UNIX operating system and are available by anonymous ftp from ftp://beagle.colorado.edu/pub/consensus.
Hertz
G Z
GZ
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA. hertz@colorado.edu
Stormo
G D
GD
D000465:Algorithms; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016014:Linear Models; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods* / Q000706:statistics & numerical data; D012984:Software
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D004269:DNA, Bacterial; D011506:Proteins; D004247:DNA