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Stop Bickering! Reconciling Signaling Pathway Databases with Network Topologies

Tobias Rubel, Pramesh Singh, View ORCID ProfileAnna Ritz
doi: https://doi.org/10.1101/2021.08.03.454954
Tobias Rubel
Biology Department, Reed College, Portland, Oregon, USA
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Pramesh Singh
Biology Department, Reed College, Portland, Oregon, USA
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Anna Ritz
Biology Department, Reed College, Portland, Oregon, USA
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Abstract

A major goal of molecular systems biology is to understand the coordinated function of genes or proteins in response to cellular signals and to understand these dynamics in the context of disease. Signaling pathway databases such as KEGG, NetPath, NCI-PID, and Panther describe the molecular interactions involved in different cellular responses. While the same pathway may be present in different databases, prior work has shown that the particular proteins and interactions differ across database annotations. However, to our knowledge no one has attempted to quantify their structural differences. It is important to characterize artifacts or other biases within pathway databases, which can provide a more informed interpretation for downstream analyses. In this work, we consider signaling pathways as graphs and we use topological measures to study their structure. We find that topological characterization using graphlets (small, connected subgraphs) distinguishes signaling pathways from appropriate null models of interaction networks. Next, we quantify topological similarity across pathway databases. Our analysis reveals that the pathways harbor database-specific characteristics implying that even though these databases describe the same pathways, they tend to be systematically different from one another. We show that pathway-specific topology can be uncovered after accounting for database-specific structure. This work present the first step towards elucidating common pathway structure beyond their specific database annotations.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/Reed-CompBio/pathway-reconciliation

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 04, 2021.
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Stop Bickering! Reconciling Signaling Pathway Databases with Network Topologies
Tobias Rubel, Pramesh Singh, Anna Ritz
bioRxiv 2021.08.03.454954; doi: https://doi.org/10.1101/2021.08.03.454954
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Stop Bickering! Reconciling Signaling Pathway Databases with Network Topologies
Tobias Rubel, Pramesh Singh, Anna Ritz
bioRxiv 2021.08.03.454954; doi: https://doi.org/10.1101/2021.08.03.454954

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