Abstract Top-down analyses in systems biology can automatically find correlations among genes and proteins in large-scale datasets. However, it is often difficult to design experiments from these results. In contrast, bottom-up approaches painstakingly craft detailed models that can be simulated computationally to suggest wet lab experiments. However, developing the models is a manual process that can take many years. These approaches have largely been developed independently. We present Linker, an efficient and automated data-driven method that can analyze molecular interactomes to propose extensions to models that can be simulated. Linker combines teleporting random walks and k-shortest path computations to discover connections from a source protein to a set of proteins collectively involved in a particular cellular process. We evaluate the efficacy of Linker by applying it to a well-known dynamic model of the cell division cycle in Saccharomyces cerevisiae. Compared to other state-of-the-art methods, subnetworks computed by Linker are heavily enriched in Gene Ontology (GO) terms relevant to the cell cycle. Finally, we highlight how networks computed by Linker elucidate the role of a protein kinase (Cdc5) in the mitotic exit network of a dynamic model of the cell cycle.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|