Exploring the Combinatorics of Motif Alignments Foraccurately Computing E-values from P-values

In biological and biomedical research motif finding tools are important in locating regulatory elements in DNA sequences. There are many such motif finding tools available, which often yield position weight matrices and significance indicators. These indicators, p-values and E-values, describe the likelihood that a motif alignment is generated by the background process, and the expected number of occurrences of the motif in the data set, respectively. The various tools often estimate these indicators differently, making them not directly comparable. One approach for comparing motifs from different tools, is computing the E-value as the product of the p-value and the number of possible alignments in the data set. In this paper we explore the combinatorics of the motif alignment models OOPS, ZOOPS, and ANR, and propose a generic algorithm for computing the number of possible combinations accurately. We also show that using the wrong alignment model can give E-values that significantly diverge from their true values. Keywords—Motif alignment, combinatorics, p-value, E-value, OOPS, ZOOPS, ANR.