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Identification of polymorphic motifs using probabilistic search algorithms
- Publication Year :
- 2005
- Publisher :
- Cold Spring Harbor Laboratory Press, 2005.
-
Abstract
- The problem of identifying motifs comprising nucleotides at a set of polymorphic DNA sites, not necessarily contiguous, arises in many human genetic problems. However, when the sites are not contiguous, no efficient algorithm exists for polymorphic motif identification. A search based on complete enumeration is computationally inefficient. We have developed probabilistic search algorithms to discover motifs of known or unknown lengths. We have developed statistical tests of significance for assessing a motif discovery, and a statistical criterion for simultaneously estimating motif length and discovering it. We have tested these algorithms on various synthetic data sets and have shown that they are very efficient, in the sense that the “true” motifs can be detected in the vast majority of replications and in a small number of iterations. Additionally, we have applied them to some real data sets and have shown that they are able to identify known motifs. In certain applications, it is pertinent to find motifs that contain contrasting nucleotides at the sites included in the motif (e.g., motifs identified in case-control association studies). For this, we have suggested appropriate modifications. Using simulations, we have discovered that the success rate of identification of the correct motif is high in case-control studies except when relative risks are small. Our analyses of evolutionary data sets resulted in the identification of some motifs that appear to have important implications on human evolutionary inference. These algorithms can easily be implemented to discover motifs from multilocus genotype data by simple numerical recoding of genotypes.
- Subjects :
- Risk
Inference
Computational biology
Herpesvirus 1, Human
Biology
DNA, Mitochondrial
Search algorithm
Genetics
Enumeration
Methods
Humans
Genetics (clinical)
Statistical hypothesis testing
Base Composition
Botswana
Polymorphism, Genetic
Small number
Probabilistic logic
Computational Biology
Genetic Variation
DNA
Synthetic data sets
Europe
Genetics, Population
Haplotypes
Receptors, LDL
Cardiovascular Diseases
Pharmacogenetics
Case-Control Studies
Africa
DNA, Viral
Motif (music)
Gilbert Disease
Algorithms
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....536f4ffe09d99bf45a7646827525b5b2