Towards Data-Integrated Cell

Natasa Przulj – Barcelona Supercomputing Center – Centro Nacional de Supercomputación (BSC-CNS)

We propose a novel, data-driven concept of an integrated cell, iCell, that integrates several types of systems-level genomic data. We construct iCells of cancers and the corresponding healty tissues. We identify new genes involved in cancer, many of which have previously been of unknown function and cannot be identified as different in cancer in any specific data type in isolation from others. We biologically validate that they have a role in cancer and find additional support via retrospective survival analyses of thousands of patients. Our methodology is universal and enables integrative comparisons of diverse molecular data over cells and tissues.

Reference

Malod-Dognin N, Petschnigg J, Windels SFL, Povh J, Hemingway H, Ketteler R & Przulj N 2019 ‘ Towards a data-integrated cell’. Nat Commun 10, 805.

Illustration of iCell. Each iCell is based on three tissue-specific molecular networks: protein–protein interaction network (PPI, in red), gene co-expression network (COEX, in blue), and genetic interaction network (GI, in green). These networks, represented by their adjacency matrices, Ai, are simultaneously decomposed as the product of three factors, G, Si, and GT (illustrated in the middle panel). From these matrix factors, we extract an integrated network, G x GT, which we call an iCell. Regions of iCells that are enriched in Reactome pathway (RP), KEGG pathway (KP), or gene ontology biological process (GO-BP) annotations (bottom).