Abstract
<p>Functional processes and mechanisms of cells are not a result of a single molecule or component but rather related to these components' complex and intricate interactions. Hence, it is beneficial to study the system as a whole. Focusing on the flow of information through a molecular interaction network using a network propagation approach, we hypothesized that the difference in such flow between control and injured conditions reveals nodes that cause a state change. We compare the difference of flow in mice with axonal injury and sham surgery. We found kinases to be enriched among source genes. Such kinases were experimentally validated for their influence in axon growth based on screening data or literature validation.<br />
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Investigating cellular activity that drives the cell to certain outcomes, we determined proteins that topologically control different human pathways represented as independent molecular interaction networks. We show that proteins that control many pathways also control the network of interaction when all pathways are combined. Such control proteins were also found to be enriched with regulatory and signaling genes, disease genes, and drug targets suggesting biological significance.<br />
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We then identify transcription factors that control different tissue-specific regulatory networks through enhancers and promoters. We show that genes regulated by promoter-controller transcription factors are tissue-specific, overexpressed in cancerous tissues, and are likely to be targeted by cancer drugs. We show that cell-type specific networks are different from tissue-specific networks based on the distribution of promoter and enhancer edges. Our method has the potential to be a significant starting point in therapeutic research in tissue-specific drug discovery.</p>