Towards a data-integrated cell.
Noël Malod-DogninJulia PetschniggSam F L WindelsJanez PovhHarry HemingwayRobin KettelerNataša PržuljPublished in: Nature communications (2019)
We are increasingly accumulating molecular data about a cell. The challenge is how to integrate them within a unified conceptual and computational framework enabling new discoveries. Hence, we propose a novel, data-driven concept of an integrated cell, iCell. Also, we introduce a computational prototype of an iCell, which integrates three omics, tissue-specific molecular interaction network types. We construct iCells of four cancers and the corresponding tissue controls and identify the most rewired genes in cancer. Many of them are of unknown function and cannot be identified as different in cancer in any specific molecular network. We biologically validate that they have a role in cancer by knockdown experiments followed by cell viability assays. We find additional support through Kaplan-Meier survival curves of thousands of patients. Finally, we extend this analysis to uncover pan-cancer genes. Our methodology is universal and enables integrative comparisons of diverse omics data over cells and tissues.
Keyphrases
- papillary thyroid
- single cell
- squamous cell
- electronic health record
- end stage renal disease
- gene expression
- lymph node metastasis
- induced apoptosis
- big data
- stem cells
- squamous cell carcinoma
- childhood cancer
- single molecule
- chronic kidney disease
- genome wide
- signaling pathway
- young adults
- peritoneal dialysis
- mesenchymal stem cells
- pi k akt
- network analysis