Adaptive Thresholding for Reconstructing Regulatory Networks from Time-Course Gene Expression Data

Discovering regulatory interactions from time-course gene expression data constitutes a canonical problem in functional genomics and systems biology. The framework of graphical Granger causality allows one to estimate such causal relationships from these data. In this study, we propose an adaptively thresholding estimates of Granger causal effects obtained from the lasso penalization method. We establish the asymptotic properties of the proposed technique, and discuss the advantages it offers over competing methods, such as the truncating lasso. Its performance and that of its competitors is assessed on a number of simulated settings and it is applied on a data set that captures the activation of T-cells.

[1]  N. Meinshausen,et al.  LASSO-TYPE RECOVERY OF SPARSE REPRESENTATIONS FOR HIGH-DIMENSIONAL DATA , 2008, 0806.0145.

[2]  C. Granger Investigating causal relations by econometric models and cross-spectral methods , 1969 .

[3]  P. Bickel,et al.  SIMULTANEOUS ANALYSIS OF LASSO AND DANTZIG SELECTOR , 2008, 0801.1095.

[4]  Helmut Ltkepohl,et al.  New Introduction to Multiple Time Series Analysis , 2007 .

[5]  Ali Shojaie,et al.  Discovering graphical Granger causality using the truncating lasso penalty , 2010, Bioinform..

[6]  Snigdhansu Chatterjee,et al.  Causality and pathway search in microarray time series experiment , 2007, Bioinform..

[7]  Korbinian Strimmer,et al.  Learning causal networks from systems biology time course data: an effective model selection procedure for the vector autoregressive process , 2007, BMC Bioinformatics.

[8]  L. Wasserman,et al.  HIGH DIMENSIONAL VARIABLE SELECTION. , 2007, Annals of statistics.

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

[10]  J. Pearl Causality: Models, Reasoning and Inference , 2000 .

[11]  Stuart J. Russell,et al.  Dynamic bayesian networks: representation, inference and learning , 2002 .

[12]  João Ricardo Sato,et al.  Modeling gene expression regulatory networks with the sparse vector autoregressive model , 2007, BMC Systems Biology.

[13]  Yan Liu,et al.  Temporal causal modeling with graphical granger methods , 2007, KDD '07.

[14]  Zoubin Ghahramani,et al.  Modeling T-cell activation using gene expression profiling and state-space models , 2004, Bioinform..

[15]  S. Geer,et al.  On the conditions used to prove oracle results for the Lasso , 2009, 0910.0722.

[16]  Aurélien Mazurie,et al.  Gene networks inference using dynamic Bayesian networks , 2003, ECCB.

[17]  Naoki Abe,et al.  Grouped graphical Granger modeling for gene expression regulatory networks discovery , 2009, Bioinform..

[18]  Shuheng Zhou Thresholded Lasso for high dimensional variable selection and statistical estimation , 2010, 1002.1583.

[19]  Ali Shojaie,et al.  Penalized likelihood methods for estimation of sparse high-dimensional directed acyclic graphs. , 2009, Biometrika.

[20]  Martin J. Wainwright,et al.  Restricted Eigenvalue Properties for Correlated Gaussian Designs , 2010, J. Mach. Learn. Res..

[21]  R. Yoshida,et al.  Finding module-based gene networks with state-space models - Mining high-dimensional and short time-course gene expression data , 2007, IEEE Signal Processing Magazine.