1. Penalized likelihood for sparse contingency tables with an application to full-length cDNA libraries
- Author
-
Corinne Dahinden, Giovanni Parmigiani, Peter Bühlmann, and Mark C. Emerick
- Subjects
Theoretical computer science ,Computer science ,Systems biology ,DNA, Recombinant ,lcsh:Computer applications to medicine. Medical informatics ,Sensitivity and Specificity ,Biochemistry ,Interaction Pattern ,Pattern Recognition, Automated ,Interaction Vector ,Bayes' theorem ,chemistry.chemical_compound ,Structural Biology ,Lasso ,Order Interaction ,MCMC Method ,Computer Graphics ,Genomic library ,Mathematical Computing ,lcsh:QH301-705.5 ,Molecular Biology ,Categorical variable ,Gene Library ,Sparse matrix ,Contingency table ,Likelihood Functions ,cDNA library ,Methodology Article ,Systems Biology ,Applied Mathematics ,Linear model ,Bayes Theorem ,Regression analysis ,Exons ,Data science ,Computer Science Applications ,Logistic Models ,lcsh:Biology (General) ,chemistry ,Pattern recognition (psychology) ,Linear Models ,Regression Analysis ,lcsh:R858-859.7 ,DNA microarray ,DNA - Abstract
Background The joint analysis of several categorical variables is a common task in many areas of biology, and is becoming central to systems biology investigations whose goal is to identify potentially complex interaction among variables belonging to a network. Interactions of arbitrary complexity are traditionally modeled in statistics by log-linear models. It is challenging to extend these to the high dimensional and potentially sparse data arising in computational biology. An important example, which provides the motivation for this article, is the analysis of so-called full-length cDNA libraries of alternatively spliced genes, where we investigate relationships among the presence of various exons in transcript species. Results We develop methods to perform model selection and parameter estimation in log-linear models for the analysis of sparse contingency tables, to study the interaction of two or more factors. Maximum Likelihood estimation of log-linear model coefficients might not be appropriate because of the presence of zeros in the table's cells, and new methods are required. We propose a computationally efficient ℓ1-penalization approach extending the Lasso algorithm to this context, and compare it to other procedures in a simulation study. We then illustrate these algorithms on contingency tables arising from full-length cDNA libraries. Conclusion We propose regularization methods that can be used successfully to detect complex interaction patterns among categorical variables in a broad range of biological problems involving categorical variables., BMC Bioinformatics, 8, ISSN:1471-2105
- Published
- 2007