A data integration methodology for systems biology
- Daehee Hwang*,
- Alistair G. Rust*,
- Stephen Ramsey*,
- Jennifer J. Smith*,
- Deena M. Leslie*,
- Andrea D. Weston*,†,
- Pedro de Atauri*,
- John D. Aitchison*,
- Leroy Hood*,‡,
- Andrew F. Siegel§, and
- Hamid Bolouri*,‡
- *Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; and §Departments of Management Science, Finance, and Statistics, University of Washington, Seattle WA 98195
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Contributed by Leroy Hood, October 5, 2005
Abstract
Different experimental technologies measure different aspects of a system and to differing depth and breadth. High-throughput assays have inherently high false-positive and false-negative rates. Moreover, each technology includes systematic biases of a different nature. These differences make network reconstruction from multiple data sets difficult and error-prone. Additionally, because of the rapid rate of progress in biotechnology, there is usually no curated exemplar data set from which one might estimate data integration parameters. To address these concerns, we have developed data integration methods that can handle multiple data sets differing in statistical power, type, size, and network coverage without requiring a curated training data set. Our methodology is general in purpose and may be applied to integrate data from any existing and future technologies. Here we outline our methods and then demonstrate their performance by applying them to simulated data sets. The results show that these methods select true-positive data elements much more accurately than classical approaches. In an accompanying companion paper, we demonstrate the applicability of our approach to biological data. We have integrated our methodology into a free open source software package named pointillist.
Footnotes
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↵ ‡ To whom correspondence may be addressed: E-mail: hbolouri{at}systemsbiology.org or lhood{at}systemsbiology.org.
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↵ † Present address: Pfizer Global Research and Development, Safety Sciences, Eastern Point Road, Groton, CT 06340.
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Conflict of interest statement: No conflicts declared.
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Abbreviations: LS, Liptak–Stouffer's; MG, Mudholkar–George's; NP, nonparametric; MM, mixture model; cdf, cumulative density function; PDF, probability density function; ESA, enhanced simulated annealing.
- Copyright © 2005, The National Academy of Sciences





