Intrinsically Multivariate Predictive Genes

Canalizing genes possess such broad regulatory power, and their action sweeps across a such a wide swath of processes that the full set of affected genes are not highly correlated under normal conditions. When not active, the controlling gene will not be predictable to any significant degree by its subject genes, either alone or in groups, since their behavior will be highly varied relative to the inactive controlling gene. When the controlling gene is active, its behavior is not well predicted by any one of its targets, but can be very well predicted by groups of genes under its control. To investigate this question, we introduce in this paper the concept of intrinsically multivariate predictive (IMP) genes, and present a mathematical study of IMP in the context of binary genes with respect to the coefficient of determination (CoD), which measures the predictive power of a set of genes with respect to a target gene. A set of predictor genes is said to be IMP for a target gene if all properly contained subsets of the predictor set are bad predictors of the target but the full predictor set predicts the target with great accuracy. We show that logic of prediction, predictive power, covariance between predictors, and the entropy of the joint probability distribution of the predictors jointly affect the appearance of IMP genes. In particular, we show that high-predictive power, small covariance among predictors, a large entropy of the joint probability distribution of predictors, and certain logics, such as XOR in the 2-predictor case, are factors that favor the appearance of IMP. The IMP concept is applied to characterize the behavior of the gene DUSP1, which exhibits control over a central, process-integrating signaling pathway, thereby providing preliminary evidence that IMP can be used as a criterion for discovery of canalizing genes.

National Science Foundation (NSF)

National Science Foundation (NSF)[CCF-0514644]

National Cancer Institute (NCI/NIH)[2 R25CA090301]

National Cancer Institute (NCI/NIH)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

CAPES (Co-ordenacao de Aperfeicoamento de Pessoal de Nivel Superior)

CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)

Translational Genomics Research Institute

Translational Genomics Research Institute