Home LiteratureArticle Details
PMID: 17559298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A survey of genomic properties for the detection of regulatory polymorphisms.

PLoS computational biology ·Vol. 3 ·No. 6 ·2007-06-00 ·Pages e106

Montgomery SB, Griffith OL, Schuetz JM, Brooks-Wilson A, Jones SJ

Abstract

Advances in the computational identification of functional noncoding polymorphisms will aid in cataloging novel determinants of health and identifying genetic variants that explain human evolution. To date, however, the development and evaluation of such techniques has been limited by the availability of known regulatory polymorphisms. We have attempted to address this by assembling, from the literature, a computationally tractable set of regulatory polymorphisms within the ORegAnno database (http://www.oreganno.org). We have further used 104 regulatory single-nucleotide polymorphisms from this set and 951 polymorphisms of unknown function, from 2-kb and 152-bp noncoding upstream regions of genes, to investigate the discriminatory potential of 23 properties related to gene regulation and population genetics. Among the most important properties detected in this region are distance to transcription start site, local repetitive content, sequence conservation, minor and derived allele frequencies, and presence of a CpG island. We further used the entire set of properties to evaluate their collective performance in detecting regulatory polymorphisms. Using a 10-fold cross-validation approach, we were able to achieve a sensitivity and specificity of 0.82 and 0.71, respectively, and we show that this performance is strongly influenced by the distance to the transcription start site.

MeSH Terms
Base Sequence Chromosome Mapping/methods DNA Mutational Analysis/methods Databases, Genetic Molecular Sequence Data Polymorphism, Single Nucleotide/genetics Regulatory Sequences, Nucleic Acid/genetics Sequence Analysis, DNA/methods
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Montgomery Stephen B
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. [email protected]
Griffith Obi L
Schuetz Johanna M
Brooks-Wilson Angela
Jones Steven J M
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Article Info
Journal
PLoS computational biology
Abbr.
PLoS Comput Biol
ISSN
1553-7358
DOI
10.1371/journal.pcbi.0030106
Email
[email protected]
Published
2007-06-00
Epub
2007-00-25
Pages
e106
Language
English
Region
United States
NLM ID
101238922
PMCID
PMC1892352
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.pcbi.0030106 PMC Full Text View journal details
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