Reconstructing distances in physical maps of chromosomes with nonoverlapping probes

John Kececioglu, Sanjay Shete, Jonathan Arnold

Research output: Contribution to conferencePaperpeer-review

10 Scopus citations

Abstract

We present a new method for reconstructing the distances between probes in physical maps of chromosomes constructed by hybridizing pairs of clones under the so-called sampling-without-replacement protocol. In this protocol, which is simple, inexpensive, and has been used to successfully map several organisms, equal-length clones are hybridized against a clone-subset called the probes. The probes are chosen by a sequential process that is designed to generate a pairwise-nonoverlapping subset of the clones. We derive a likelihood function on probe spacings and orders for this protocol under a natural model of hybridization error, and describe how to reconstruct the most likely spacing for a given order under this objective using continuous optimization. The approach is tested on simulated data and real data from chromosome VI of Aspergillus nidulans. On simulated data we recover the true order and close to the true spacing; on the real data, for which the true order and spacing is unknown, we recover a probe order differing significantly from the published one. To our knowledge this is the first practical approach for computing a globally-optimal maximum-likelihood reconstruction of interprobe distances from clone-probe hybridization data.

Original languageEnglish (US)
Pages183-192
Number of pages10
StatePublished - Jan 1 2000
Externally publishedYes
EventRECOMB 2000: 4th Annual International Conference on Computational Molecular Biology - Tokyo, Jpn
Duration: Apr 8 2000Apr 11 2000

Other

OtherRECOMB 2000: 4th Annual International Conference on Computational Molecular Biology
CityTokyo, Jpn
Period4/8/004/11/00

ASJC Scopus subject areas

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

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