Significance of inter-species matches when evolutionary rate varies

Jia Li, Webb Miller

Research output: Contribution to conferencePaperpeer-review

7 Scopus citations

Abstract

We develop techniques to estimate the statistical significance of gap-free alignments between two genomic DNA sequences, using human-mouse alignments as an example. The sequences are assumed to be sufficiently similar that some but not all of the neutrally evolving regions (i.e., those under no evolutionary constraint) can be reliably aligned. Our goal is to model the situation in which the neutral rate of evolution, and hence the extent of the aligning intervals, varies across the genome. In some cases, this permits the weaker of two matches to be judged as less likely to have arisen by chance, provided it lies in a genomic interval with a high level of background divergence. We employ a Hidden Markov Model to capture variations in divergence rates, and assign probability values to gap-free alignments using techniques related to those used for the same purpose by Blast. Our methods are illustrated in detail using a 1.49 Mb genomic region. Preliminary results using all of human chromosome 22 indicate that these techniques will work for the entire human genome.

Original languageEnglish (US)
Pages216-224
Number of pages9
DOIs
StatePublished - 2002
EventRECOMB 2002: Proceedings of the Sixth Annual International Conference on Computational Biology - Washington, DC, United States
Duration: Apr 18 2002Apr 21 2002

Other

OtherRECOMB 2002: Proceedings of the Sixth Annual International Conference on Computational Biology
Country/TerritoryUnited States
CityWashington, DC
Period4/18/024/21/02

All Science Journal Classification (ASJC) codes

  • Computer Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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