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JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
Published on: October 19, 2021
A context-sensitive framework for the analysis of human signalling pathways in molecular interaction networks
Alexander Lan1, Michal Ziv-Ukelson, Esti Yeger-Lotem
1Department of Computer Science, National Center for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Bioinformatics (Oxford, England)
|July 2, 2013
Summary
Systems biology faces challenges in linking molecular interactions to cellular behaviors. A new context-sensitive network model, ContextNet, identifies signaling pathways and their specific cellular contexts, improving understanding of biological responses.
Area of Science:
- Systems Biology
- Network Biology
- Computational Biology
Background:
- Current systems biology models use static interaction scores, failing to capture dynamic protein partnerships in different cellular conditions.
- Understanding cellular pathways is crucial for linking molecular interactions to specific phenotypes and behaviors.
Purpose of the Study:
- To develop a novel context-sensitive network model for systems biology.
- To create a computational tool, ContextNet, for identifying context-specific signaling pathways.
- To enhance the understanding of cellular responses to stimuli by incorporating context-dependent interactions.
Main Methods:
- Developed a context-sensitive network model assigning multiple contexts to genes/proteins and context-sensitive scores to interactions.
- Implemented a dynamic programming algorithm within the ContextNet tool to identify signaling paths.
- Validated the model using 18,348 curated cellular paths from the SPIKE database.
Main Results:
- ContextNet successfully identifies high-ranking context-sensitive paths in the interactome.
- The model revealed intermediate proteins and their path-specific contexts.
- Application to influenza infection in lung cells highlighted infection-related proteins and identified known/putative viral response mechanisms.
Conclusions:
- Context sensitivity is a vital extension for current network biology models.
- ContextNet efficiently elucidates cellular response mechanisms by considering dynamic interactions.
- The approach provides a powerful framework for dissecting complex biological pathways.
Related Concept Videos
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:19Contact-dependent Signaling
Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions
In animal cells, gap junctions are formed...
02:04Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...