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Motivation : Molecular signatures for diagnosis or prognosis estimated from large-scale gene expression data often lack robustness and stability, rendering their biological interpretation challenging. Increasing the signatures interpretability and stability across perturbations of a given dataset and, if possible, across datasets, is urgently needed to ease the discovery of important biological processes and, eventually, new drug targets. Results : We propose a new method to construct signatures with increased stability and easier interpretability. The method uses a gene network as side interpretation and enforces a large connectivity among the genes in the signature, leading to signatures typically made of genes clustered in a few subnetworks. It combines the recently proposed graph Lasso procedure with a stability selection procedure. We evaluate its relevance for the estimation of a prognostic signature in breast cancer, and highlight in particular the increase in interpretability and stability of the signature.
Tissue heterogeneity is a major confounding factor in studying individual populations that cannot be resolved directly by global profiling. Experimental solutions to mitigate tissue heterogeneity are expensive, time consuming, inapplicable to existin
Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The chemical synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequentl
Motivation: Histone modifications are among the most important factors that control gene regulation. Computational methods that predict gene expression from histone modification signals are highly desirable for understanding their combinatorial effec
When dealing with large scale gene expression studies, observations are commonly contaminated by unwanted variation factors such as platforms or batches. Not taking this unwanted variation into account when analyzing the data can lead to spurious ass