Computational strategy for discovering druggable gene networks from genome-wide RNA expression profiles

Seiya Imoto, Yoshinor Tamada, Hiromitsu Araki, Kaori Yasuda, Cristin G. Print, Stephen D. Charnock-Jones, Deborah Sanders, Christopher J. Savoie, Kousuke Tashiro, Satoru Kuhara, Satoru Miyano

研究成果: Chapter in Book/Report/Conference proceedingConference contribution

26 被引用数 (Scopus)

抄録

We propose a computational strategy for discovering gene networks affected by a chemical compound. Two kinds of DNA microarray data are assumed to be used: One dataset is short time-course data that measure responses of genes following an experimental treatment. The other dataset is obtained by several hundred single gene knock-downs. These two datasets provide three kinds of information; (i) A gene network is estimated from time-course data by the dynamic Bayesian network model, (ii) Relationships between the knocked-down genes and their regulatees are estimated directly from knock-down microarrays and (iii) A gene network can be estimated by gene knock-down data alone using the Bayesian network model. We propose a method that combines these three kinds of information to provide an accurate gene network that most strongly relates to the mode-of-action of the chemical compound in cells. This information plays an essential role in pharmacogenomics. We illustrate this method with an actual example where human endothelial cell gene networks were generated from a novel time course of gene expression following treatment with the drug fenofibrate, and from 270 novel gene knock-downs. Finally, we succeeded in inferring the gene network related to PPAR-a, which is a known target of fenofibrate.

本文言語英語
ホスト出版物のタイトルProceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006
ページ559-571
ページ数13
出版ステータス出版済み - 2006
イベント11th Pacific Symposium on Biocomputing 2006, PSB 2006 - Maui, HI, 米国
継続期間: 1 3 20061 7 2006

出版物シリーズ

名前Proceedings of the Pacific Symposium on Biocomputing 2006, PSB 2006

その他

その他11th Pacific Symposium on Biocomputing 2006, PSB 2006
Country米国
CityMaui, HI
Period1/3/061/7/06

All Science Journal Classification (ASJC) codes

  • Computational Theory and Mathematics
  • Biomedical Engineering
  • Medicine(all)

フィンガープリント 「Computational strategy for discovering druggable gene networks from genome-wide RNA expression profiles」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル