Modeling Liquid Association
Article first published online: 1 JUN 2010
© 2010, The International Biometric Society
Volume 67, Issue 1, pages 133–141, March 2011
How to Cite
Ho, Y.-Y., Parmigiani, G., Louis, T. A. and Cope, L. M. (2011), Modeling Liquid Association. Biometrics, 67: 133–141. doi: 10.1111/j.1541-0420.2010.01440.x
- Issue published online: 14 MAR 2011
- Article first published online: 1 JUN 2010
- Received August 2009. Revised March 2010. Accepted March 2010.
- Gene expression;
- Generalized estimating equations;
- Higher-order interaction;
- Liquid association;
- Non-Gaussian multivariate distribution
Summary In 2002, Ker–Chau Li introduced the liquid association measure to characterize three-way interactions between genes, and developed a computationally efficient estimator that can be used to screen gene expression microarray data for such interactions. That study, and others published since then, have established the biological validity of the method, and clearly demonstrated it to be a useful tool for the analysis of genomic data sets. To build on this work, we have sought a parametric family of multivariate distributions with the flexibility to model the full range of trivariate dependencies encompassed by liquid association. Such a model could situate liquid association within a formal inferential theory. In this article, we describe such a family of distributions, a trivariate, conditional normal model having Gaussian univariate marginal distributions, and in fact including the trivariate Gaussian family as a special case. Perhaps the most interesting feature of the distribution is that the parameterization naturally parses the three-way dependence structure into a number of distinct, interpretable components. One of these components is very closely aligned to liquid association, and is developed as a measure we call modified liquid association. We develop two methods for estimating this quantity, and propose statistical tests for the existence of this type of dependence. We evaluate these inferential methods in a set of simulations and illustrate their use in the analysis of publicly available experimental data.