Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-6-22
pubmed:abstractText
The classic algorithms of Needleman-Wunsch and Smith-Waterman find a maximum a posteriori probability alignment for a pair hidden Markov model (PHMM). To process large genomes that have undergone complex genome rearrangements, almost all existing whole genome alignment methods apply fast heuristics to divide genomes into small pieces that are suitable for Needleman-Wunsch alignment. In these alignment methods, it is standard practice to fix the parameters and to produce a single alignment for subsequent analysis by biologists. As the number of alignment programs applied on a whole genome scale continues to increase, so does the disagreement in their results. The alignments produced by different programs vary greatly, especially in non-coding regions of eukaryotic genomes where the biologically correct alignment is hard to find. Parametric alignment is one possible remedy. This methodology resolves the issue of robustness to changes in parameters by finding all optimal alignments for all possible parameters in a PHMM. Our main result is the construction of a whole genome parametric alignment of Drosophila melanogaster and Drosophila pseudoobscura. This alignment draws on existing heuristics for dividing whole genomes into small pieces for alignment, and it relies on advances we have made in computing convex polytopes that allow us to parametrically align non-coding regions using biologically realistic models. We demonstrate the utility of our parametric alignment for biological inference by showing that cis-regulatory elements are more conserved between Drosophila melanogaster and Drosophila pseudoobscura than previously thought. We also show how whole genome parametric alignment can be used to quantitatively assess the dependence of branch length estimates on alignment parameters.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-10325427, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-12466850, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-12529312, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-12824358, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-15057822, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-15534223, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-15572468, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-15608223, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-15632085, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-1631095, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-5420325, http://linkedlifedata.com/resource/pubmed/commentcorrection/16789815-8743701
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1553-7358
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e73
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Parametric alignment of Drosophila genomes.
pubmed:affiliation
Department of Electrical Engineering and Computer Sciences, University of California Berkeley, Berkeley, California, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural