Modeling genetic networks from clonal analysis

Radhakrishnan Nagarajan, Jane E. Aubin, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In this report a systematic approach is used to determine the approximate genetic network and robust dependencies underlying differentiation. The data considered is in the form of a binary matrix and represent the expression of the nine genes across the 99 colonies. The report is divided into two parts: the first part identifies significant pair-wise dependencies from the given binary matrix using linear correlation and mutual information. A new method is proposed to determine statistically significant dependencies estimated using the mutual information measure. In the second, a Bayesian approach is used to obtain an approximate description (equivalence class) of network structures. The robustness of linear correlation, mutual information and the equivalence class of networks is investigated with perturbation and decreasing colony number. Perturbation of the data was achieved by generating bootstrap realizations. The results are refined with biological knowledge. It was found that certain dependencies in the network are immune to perturbation and decreasing colony number and may represent robust features, inherent in the differentiation program of osteoblast progenitor cells. The methods to be discussed are generic in nature and not restricted to the experimental paradigm addressed in this study.

Original languageEnglish
Pages (from-to)359-373
Number of pages15
JournalJournal of Theoretical Biology
Volume230
Issue number3
DOIs
StatePublished - Oct 7 2004

Bibliographical note

Funding Information:
We would also like to thank Kevin Murphy and Philip Leray for making available their Matlab routines, and the Arkansas Cancer Research Center (ACRC) differentiation group for useful discussions. This research was supported in part by funds provided to the UAMS Microarray Facility through Act 1, The Arkansas Tobacco Settlement Proceeds Act of 2000, by NIH Grant #P20 RR-16460 from the BRIN Program of the National Center for Research Resources and by an NIH grant to CAP (AG20941).

Keywords

  • Bayesian networks
  • Clonal analysis
  • Linear correlation
  • Mutual information
  • Osteoblast differentiation

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics

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