BRANE Clust: Cluster-Assisted Gene Regulatory Network Inference Refinement

Aurélie Pirayre (1) , Camille Couprie (2) , Laurent Duval (1) , Jean-Christophe Pesquet (3, 4, 5)

1 IFPEN - IFP Energies nouvelles
2 FAIR - Facebook AI Research [Paris]
3 GALEN - Organ Modeling through Extraction, Representation and Understanding of Medical Image Content
4 GALEN-POST - Organ Modeling through Extraction, Representation and Understanding of Medical Image Content
5 LIGM - Laboratoire d'Informatique Gaspard-Monge

Discovering meaningful gene interactions is crucial for the identification of novel regulatory processes in cells. Building accurately the related graphs remains challenging due to the large number of possible solutions from available data. Nonetheless, enforcing a priori on the graph structure, such as modularity, may reduce network indeterminacy issues. BRANE Clust (Biologically-Related A priori Network Enhancement with Clustering) refines gene regulatory network (GRN) inference thanks to cluster information. It works as a post-processing tool for inference methods (i.e. CLR, GENIE3). In BRANE Clust, the clustering is based on the inversion of a linear system of equations involving a graph-Laplacian matrix promoting a modular structure. Our approach is validated on DREAM4 and DREAM5 datasets with objective measures, showing significant comparative improvements. We provide additional insights on the discovery of novel regulatory or co-expressed links in the inferred Escherichia coli network evaluated using the STRING database. The comparative pertinence of clustering is discussed computationally (SIMONE, WGCNA, X-means) and biologically (RegulonDB). BRANE Clust software is available at http://www-syscom.univ-mlv.fr/~pirayre/Codes-GRN-BRANE-clust.html

Keywords: Transcriptomic data; Combinatorial optimization; network inference; Graph Clustering; Gene regulation network; DREAM Challenge

Domains: Signal and Image Processing; Bioinformatics [q-bio.QM]; Machine Learning [stat.ML]

Aurélie Pirayre, Camille Couprie, Laurent Duval, Jean-Christophe Pesquet. BRANE Clust: Cluster-Assisted Gene Regulatory Network Inference Refinement. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2018, 15 (3), pp.850-860. ⟨10.1101/114769⟩. ⟨hal-01330638⟩