Combining evidence using p-values: application to sequence homology searches.

Abstract

In sequence analysis, two or more (approximately) independent measures of the membership of a sequence (or sequence region) in some class are often available. We would like to estimate the likelihood of the sequence being a member of the class in view of all the available evidence. An example is estimating the significance of the observed match of a macromolecular sequence (DNA or protein) to a set of patterns (motifs) that characterize a biological sequence family. An intuitive way to do this is to express each piece of evidence as a p-value, and then use the product of these p-values as the measure of membership in the family. We derive a formula and algorithm (QFAST) for calculating the statistical distribution of the product of n independent p-values. We demonstrate that sorting sequences by this p-value effectively combines the information present in multiple motifs, leading to highly accurate and sensitive sequence homology searches.

Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal Organization, Vesicular Trafficking, Nucleocytosolic Shuttling, and Chromosome Activity

“…MEME represents motifs, a sequence pattern that occurs repeatedly in a group of related protein sequences, as position-dependent letter-probability matrices describing the probability of each possible letter at each position in the pattern. MEME uses statistical modeling techniques to automatically choose the best width and description for each motif [55]. Secondary structure was predicted by PHD, which includes protein family information in the prediction [56, New amino acid and DNA sequences generated from the yeast two-hybrid system were initially subjected to BLAST search [58], then to the MAXHOM multiple sequence alignment and 3D-PSSM (three-dimensional position-specific scoring matrix) search methods.…”

The apoptosis database

“…In Smac, the N-terminal four amino acids (after loss of a targeting domain) are required for the activity of the full-length protein and seven amino acids are sufficient for activity as a peptide. 15 Methods such as MEME 16 search and recognize biologically relevant short motifs of this nature and will expand the characterization methodology used in a future version of the database.…”

“…Asymmetric shapes (trapezoids) are manual curation processes nr database is used to create dynamic profiles. The PSI-BLAST profiles are robust and dynamic enough to gather all known domains when several (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) profiles are used to represent each domain. The initial round of iterative profile building always starts with a single seed sequence.…”

Crop Improvement through Modification of the Plant's Own Genome

“…Publicly available databases including those maintained by the National Center for Biotechnology Information and SANGER were searched for T-DNA border sequences using the Motif Alignment and Search Tool (Bailey and Gribskov, 1998) and advanced BLASTN (penalty for nucleotide mismatch 5 21; expect 5 10 5 ; Altschul et al, 1997).…”