Discovering statistically significant biclusters in gene expression data.
In gene expression data, a bicluster is a subset of the genes exhibiting consistent patterns over a subset of the conditions. We propose a new method to detect significant biclusters in large expression datasets. Our approach is graph theoretic coupled with statistical modelling of the data. Under plausible assumptions, our algorithm is polynomial and is guaranteed to find the most significant biclusters. We tested our method on a collection of yeast expression profiles and on a human cancer dataset. Cross validation results show high specificity in assigning function to genes based on their biclusters, and we are able to annotate in this way 196 uncharacterized yeast genes. We also demonstrate how the biclusters lead to detecting new concrete biological associations. In cancer data we are able to detect and relate finer tissue types than was previously possible. We also show that the method outperforms the biclustering algorithm of Cheng and Church (2000).
Tanay
Amos
A
School Of Computer Science, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, 69978, Israel. amos@tau.ac.il
Sharan
Roded
R
Shamir
Ron
R
D000465:Algorithms; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008223:Lymphoma / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D015003:Yeasts / Q000235:genetics