Sylvain Blachon

Strong-association-rule mining for large-scale gene-expression data analysis: a case study on human SAGE data

BackgroundThe association-rules discovery (ARD) technique has yet to be applied to gene-expression data analysis. Even in the absence of previous biological knowledge, it should identify sets of genes whose expression is correlated. The first association-rule miners appeared six years ago and proved efficient at dealing with sparse and weakly correlated data. A huge international research effort has led to new algorithms for tackling difficult contexts and these are particularly suited to analysis of large gene-expression matrices. To validate the ARD technique we have applied it to freely available human serial analysis of gene expression (SAGE) data.ResultsThe approach described here enables us to designate sets of strong association rules. We normalized the SAGE data before applying our association rule miner. Depending on the discretization algorithm used, different properties of the data were highlighted. Both common and specific interpretations could be made from the extracted rules. In each and every case the extracted collections of rules indicated that a very strong co-regulation of mRNA encoding ribosomal proteins occurs in the dataset. Several rules associating proteins involved in signal transduction were obtained and analyzed, some pointing to yet-unexplored directions. Furthermore, by examining a subset of these rules, we were able both to reassign a wrongly labeled tag, and to propose a function for an expressed sequence tag encoding a protein of unknown function.ConclusionsWe show that ARD is a promising technique that turns out to be complementary to existing gene-expression clustering techniques.

Mining Plausible Patterns from Genomic Data

The discovery of biologically interpretable knowledge from gene expression data is one of the largest contemporary genomic challenges. As large volumes of expression data are being generated, there is a great need for automated tools that provide the means to analyze them. However, the same tools can provide an overwhelming number of candidate hypotheses which can hardly be manually exploited by an expert. An additional knowledge helping to focus automatically on the most plausible candidates only can up-value the experiment significantly. Background knowledge available in literature databases, biological ontologies and other sources can be used for this purpose. In this paper we propose and verify a methodology that enables to effectively mine and represent meaningful over-expression patterns. Each pattern represents a bi-set of a gene group over-expressed in a set of biological situations. The originality of the framework consists in its constraint-based nature and an effective cross-fertilization of constraints based on expression data and background knowledge. The result is a limited set of candidate patterns that are most likely interpretable by biologists. Supplemental automatic interpretations serve to ease this process. Various constraints can generate plausible pattern sets of different characteristics