Jon D McAuliffe | PubMed Health

PubMed2005

Subtree power analysis and species selection for comparative genomics.

Sequence comparison across multiple organisms aids in the detection of regions under selection. However, resource limitations require a prioritization of genomes to be sequenced. This prioritization should be grounded in two considerations: the lineal scope encompassing the biological phenomena of interest, and the optimal species within that scope for detecting functional elements. We introduce a statistical framework for optimal species subset selection, based on maximizing power to detect conserved sites. Analysis of a phylogenetic star topology shows theoretically that the optimal species subset is not in general the most evolutionarily diverged subset. We then demonstrate this finding empirically in a study of vertebrate species. Our results suggest that marsupials are prime sequencing candidates.

Animals↗

PubMed2004

Multiple-sequence functional annotation and the generalized hidden Markov phylogeny.

MOTIVATION: Phylogenetic shadowing is a comparative genomics principle that allows for the discovery of conserved regions in sequences from multiple closely related organisms. We develop a formal probabilistic framework for combining phylogenetic shadowing with feature-based functional annotation methods. The resulting model, a generalized hidden Markov phylogeny (GHMP), applies to a variety of situations where functional regions are to be inferred from evolutionary constraints. RESULTS: We show how GHMPs can be used to predict complete shared gene structures in multiple primate sequences. We also describe shadower, our implementation of such a prediction system. We find that shadower outperforms previously reported ab initio gene finders, including comparative human-mouse approaches, on a small sample of diverse exonic regions. Finally, we report on an empirical analysis of shadower's performance which reveals that as few as five well-chosen species may suffice to attain maximal sensitivity and specificity in exon demarcation. AVAILABILITY: A Web server is available at http://bonaire.lbl.gov/shadower

Algorithms↗