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Journal of Computational Biology
Article . 2013 . Peer-reviewed
License: Mary Ann Liebert TDM
Data sources: Crossref
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Top-Down Network Analysis to Drive Bottom-Up Modeling of Physiological Processes

Authors: T. M. Murali; John J. Tyson; Christopher L. Poirel; Richard R. Rodrigues; Katherine C. Chen;

Top-Down Network Analysis to Drive Bottom-Up Modeling of Physiological Processes

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.

Related Organizations
Keywords

Saccharomyces cerevisiae Proteins, Gene Expression Regulation, Fungal, Cell Cycle, Cell Cycle Proteins, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Models, Biological

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    11
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Average
Top 10%
Top 10%
bronze