TY - JOUR
T1 - Static network structure can be used to model the phenotypic effects of perturbations in regulatory networks
AU - Feiglin, Ariel
AU - Hacohen, Adar
AU - Sarusi, Avital
AU - Fisher, Jasmin
AU - Unger, Ron
AU - Ofran, Yanay
N1 - Funding Information:
Funding: This work is supported by Microsoft Research.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - Motivation: Biological processes are dynamic, whereas the networks that depict them are typically static. Quantitative modeling using differential equations or logic-based functions can offer quantitative predictions of the behavior of biological systems, but they require detailed experimental characterization of interaction kinetics, which is typically unavailable. To determine to what extent complex biological processes can be modeled and analyzed using only the static structure of the network (i.e. The direction and sign of the edges), we attempt to predict the phenotypic effect of perturbations in biological networks from the static network structure.Results: We analyzed three networks from different sources: The EGFR/MAPK and PI3K/AKT network from a detailed experimental study, the TNF regulatory network from the STRING database and a large network of all NCI-curated pathways from the Protein Interaction Database. Altogether, we predicted the effect of 39 perturbations (e.g. by one or two drugs) on 433 target proteins/genes. In up to 82 of the cases, an algorithm that used only the static structure of the network correctly predicted whether any given protein/gene is upregulated or downregulated as a result of perturbations of other proteins/genes.Conclusion: While quantitative modeling requires detailed experimental data and heavy computations, which limit its scalability for large networks, a wiring-based approach can use available data from pathway and interaction databases and may be scalable. These results lay the foundations for a large-scale approach of predicting phenotypes based on the schematic structure of networks.Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
AB - Motivation: Biological processes are dynamic, whereas the networks that depict them are typically static. Quantitative modeling using differential equations or logic-based functions can offer quantitative predictions of the behavior of biological systems, but they require detailed experimental characterization of interaction kinetics, which is typically unavailable. To determine to what extent complex biological processes can be modeled and analyzed using only the static structure of the network (i.e. The direction and sign of the edges), we attempt to predict the phenotypic effect of perturbations in biological networks from the static network structure.Results: We analyzed three networks from different sources: The EGFR/MAPK and PI3K/AKT network from a detailed experimental study, the TNF regulatory network from the STRING database and a large network of all NCI-curated pathways from the Protein Interaction Database. Altogether, we predicted the effect of 39 perturbations (e.g. by one or two drugs) on 433 target proteins/genes. In up to 82 of the cases, an algorithm that used only the static structure of the network correctly predicted whether any given protein/gene is upregulated or downregulated as a result of perturbations of other proteins/genes.Conclusion: While quantitative modeling requires detailed experimental data and heavy computations, which limit its scalability for large networks, a wiring-based approach can use available data from pathway and interaction databases and may be scalable. These results lay the foundations for a large-scale approach of predicting phenotypes based on the schematic structure of networks.Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
UR - http://www.scopus.com/inward/record.url?scp=84868007855&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/bts517
DO - 10.1093/bioinformatics/bts517
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C2 - 22923292
AN - SCOPUS:84868007855
SN - 1367-4803
VL - 28
SP - 2811
EP - 2818
JO - Bioinformatics
JF - Bioinformatics
IS - 21
ER -