Revising Qualitative Models of Gene Regulation

We present an approach to revising qualitative causal models of gene regulation with DNA microarray data. The method combines search through a space of variable orderings with search through a space of parameters on causal links, with weight decay driving the model toward integer values. We illustrate the technique on a model of photosynthesis regulation and associated microarray data. Experiments with synthetic data that varied distance from the target model, noise, and number of training cases suggest the method is robust with respect to these factors. In closing, we suggest directions for future research and discuss related work on inducing causal regulatory models.

[1]  Satoru Miyano,et al.  Estimation of Genetic Networks and Functional Structures Between Genes by Using Bayesian Networks and Nonparametric Regression , 2001, Pacific Symposium on Biocomputing.

[2]  C. Jansson,et al.  Engineering of the protein environment around the redox-active TyrZ in photosystem II. The role of F186 and P162 in the D1 protein of Synechocystis 6803. , 2001, European journal of biochemistry.

[3]  Kazumi Saito,et al.  Computational Discovery of Communicable Scientific Knowledge , 2002 .

[4]  Jorma Rissanen,et al.  Stochastic Complexity in Statistical Inquiry , 1989, World Scientific Series in Computer Science.

[5]  J. Shaffer Multiple Hypothesis Testing , 1995 .

[6]  David Page,et al.  Modelling regulatory pathways in E. coli from time series expression profiles , 2002, ISMB.

[7]  K. Saito,et al.  MDL regularizer: a new regularizer based on the MDL principle , 1997, Proceedings of International Conference on Neural Networks (ICNN'97).

[8]  Ashesh Mahidadia,et al.  Assisting Model-Discovery in Neuroendocrinology , 2001, Discovery Science.

[9]  Tommi S. Jaakkola,et al.  Combining Location and Expression Data for Principled Discovery of Genetic Regulatory Network Models , 2001, Pacific Symposium on Biocomputing.

[10]  Michal Linial,et al.  Using Bayesian Networks to Analyze Expression Data , 2000, J. Comput. Biol..

[11]  Arthur R. Grossman,et al.  Tracking the Light Environment by Cyanobacteria and the Dynamic Nature of Light Harvesting* , 2001, The Journal of Biological Chemistry.

[12]  John R. Koza,et al.  Reverse Engineering of Metabolic Pathways from Observed Data Using Genetic Programming , 2000, Pacific Symposium on Biocomputing.

[13]  Satoru Miyano,et al.  Bayesian network and nonparametric heteroscedastic regression for nonlinear modeling of genetic network , 2003, Proceedings. IEEE Computer Society Bioinformatics Conference.

[14]  Ivan Bratko,et al.  Abductive Inference of Genetic Networks , 2001, AIME.

[15]  Kazumi Saito,et al.  Computational Revision of Quantitative Scientific Models , 2001, Discovery Science.