Title
Discovering graphical Granger causality using the truncating lasso penalty.
Abstract
Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem in systems biology. Whole-genome expression data over time provides an opportunity to determine how the expression levels of genes are affected by changes in transcription levels of other genes, and can therefore be used to discover regulatory interactions among genes.In this article, we propose a novel penalization method, called truncating lasso, for estimation of causal relationships from time-course gene expression data. The proposed penalty can correctly determine the order of the underlying time series, and improves the performance of the lasso-type estimators. Moreover, the resulting estimate provides information on the time lag between activation of transcription factors and their effects on regulated genes. We provide an efficient algorithm for estimation of model parameters, and show that the proposed method can consistently discover causal relationships in the large p, small n setting. The performance of the proposed model is evaluated favorably in simulated, as well as real, data examples.The proposed truncating lasso method is implemented in the R-package 'grangerTlasso' and is freely available at http://www.stat.lsa.umich.edu/~shojaie/.
Year
DOI
Venue
2010
10.1093/bioinformatics/btq377
Bioinformatics
Keywords
Field
DocType
regulatory interaction,truncating lasso penalty,novel penalization method,expression level,proposed penalty,whole-genome expression data,data example,proposed truncating lasso method,causal relationship,transcription factor,system biology,time series,biological systems,granger causality
Data mining,Inference,Regression analysis,Computer science,Granger causality,Lasso (statistics),Systems biology,Bioinformatics,Gene regulatory network,Gene expression profiling,Estimator
Journal
Volume
Issue
ISSN
26
18
1367-4811
Citations 
PageRank 
References 
25
1.31
12
Authors
2
Name
Order
Citations
PageRank
Shojaie, Ali1668.96
George Michailidis230335.19