TY - JOUR

T1 - Identifying DNA and protein patterns with statistically significant alignments of multiple sequences

AU - Hertz, Gerald Z.

AU - Stormo, Gary D.

PY - 1999

Y1 - 1999

N2 - Motivation: 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 Escherichia coli CRP protein. Availability: Programs were developed under the UNIX operating system and are available by anonymous ftp from ftp://beagle.colorado.edu/pub/consensus.

AB - Motivation: 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 Escherichia coli CRP protein. Availability: Programs were developed under the UNIX operating system and are available by anonymous ftp from ftp://beagle.colorado.edu/pub/consensus.

UR - http://www.scopus.com/inward/record.url?scp=0032826179&partnerID=8YFLogxK

U2 - 10.1093/bioinformatics/15.7.563

DO - 10.1093/bioinformatics/15.7.563

M3 - Article

C2 - 10487864

AN - SCOPUS:0032826179

VL - 15

SP - 563

EP - 577

JO - Bioinformatics

JF - Bioinformatics

SN - 1367-4803

IS - 7-8

ER -