A bi-ordering approach to linking gene expression with clinical annotations in gastric cancer

Fan Shi, Christopher Leckie, Geoff MacIntyre, Izhak Haviv, Alex Boussioutas, Adam Kowalczyk

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: In the study of cancer genomics, gene expression microarrays, which measure thousands of genes in a single assay, provide abundant information for the investigation of interesting genes or biological pathways. However, in order to analyze the large number of noisy measurements in microarrays, effective and efficient bioinformatics techniques are needed to identify the associations between genes and relevant phenotypes. Moreover, systematic tests are needed to validate the statistical and biological significance of those discoveries.Results: In this paper, we develop a robust and efficient method for exploratory analysis of microarray data, which produces a number of different orderings (rankings) of both genes and samples (reflecting correlation among those genes and samples). The core algorithm is closely related to biclustering, and so we first compare its performance with several existing biclustering algorithms on two real datasets - gastric cancer and lymphoma datasets. We then show on the gastric cancer data that the sample orderings generated by our method are highly statistically significant with respect to the histological classification of samples by using the Jonckheere trend test, while the gene modules are biologically significant with respect to biological processes (from the Gene Ontology). In particular, some of the gene modules associated with biclusters are closely linked to gastric cancer tumorigenesis reported in previous literature, while others are potentially novel discoveries.Conclusion: In conclusion, we have developed an effective and efficient method, Bi-Ordering Analysis, to detect informative patterns in gene expression microarrays by ranking genes and samples. In addition, a number of evaluation metrics were applied to assess both the statistical and biological significance of the resulting bi-orderings. The methodology was validated on gastric cancer and lymphoma datasets.

Original languageEnglish
Article number477
JournalBMC Bioinformatics
StatePublished - 23 Sep 2010
Externally publishedYes

Bibliographical note

Funding Information:
National ICT Australia (NICTA) is funded by the Australian Government’s Department of Communications, Information Technology and the Arts and the Australian Council through Backing Australia’s Ability and the ICT Center of Excellence program. This paper is an extended version of a previous paper in the 2nd International Workshop on Machine Learning in Systems Biology.


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