Discovering Graphical Granger Causality Using the Truncating Lasso Penalty

TL;DR

This paper introduces a novel truncating lasso penalty for estimating causal gene interactions from time-course expression data, accurately determining the order and time lag of regulatory relationships.

Contribution

It proposes a new penalization method that correctly identifies the order of time series and improves causal inference in high-dimensional gene expression data.

Findings

Accurately determines the order of time series data.

Improves causal relationship detection in high-dimensional settings.

Performs well in both simulated and real data examples.

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 paper, 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 available at http://www.stat.lsa.umich.edu/~shojaie.