Disease Module in the Human Interactome
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About This MicroSim
This MicroSim visualizes the disease module hypothesis — the idea that genes associated with the same disease tend to cluster together in the human protein-protein interaction network (interactome). Two disease modules (asthma in blue and diabetes in red) are highlighted within a ~30-protein interactome subset, with overlap proteins shown in purple.
The Disease Module Hypothesis
Proposed by Barabasi and colleagues, this hypothesis states that:
- Disease genes are not randomly scattered across the interactome — they form localized modules
- The closer two disease modules are in the network, the more likely the diseases share biological mechanisms and comorbidity
- Overlap proteins (in both modules) suggest shared molecular mechanisms between diseases
Visual Encoding
- Blue nodes — Proteins associated with asthma
- Red nodes — Proteins associated with diabetes
- Purple nodes — Overlap proteins associated with both diseases
- Gray nodes — Background interactome proteins (not disease-associated)
- Network proximity score — A metric quantifying how close the two disease modules are
How to Use
- Toggle disease modules — Show or hide each disease module to see its proteins highlighted in the interactome
- Hover over nodes to see protein names and disease associations
- Identify overlap — Find purple nodes that belong to both disease modules
- Drag and zoom to explore the network layout
- Read the proximity score — Low proximity indicates the modules are close (diseases may share mechanisms); high proximity indicates distant modules
Suggested Exploration
- Toggle only asthma ON — observe how its associated proteins cluster together rather than scattering randomly
- Toggle both ON — find the purple overlap proteins and consider what shared biology they might represent
- Look at the network distance between the two modules — are they adjacent or separated by many hops?
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Lesson Plan
Grade Level
College introductory bioinformatics
Duration
15-20 minutes
Prerequisites
- Understanding of protein-protein interaction networks
- Basic knowledge of complex diseases and genetic risk factors
- Familiarity with network metrics (degree, distance)
Activities
- Exploration (5 min): Toggle each disease module on separately. Does each module form a connected cluster, or are its proteins scattered? What does this observation support?
- Overlap Analysis (5 min): Toggle both modules on. Identify all overlap proteins (purple). Research one of these proteins — is it known to play a role in both diseases?
- Discussion (5 min): The network proximity between two disease modules can predict disease comorbidity. If asthma and diabetes modules are close, what might this suggest about patients who have both conditions?
- Assessment (5 min): Answer the reflection questions below.
Assessment
- What is the disease module hypothesis, and what evidence supports it?
- Why do overlap proteins between disease modules suggest shared molecular mechanisms?
- How could network proximity between disease modules be used to predict drug repurposing opportunities?
- If a newly discovered disease gene is adjacent to an existing disease module in the interactome, what would you predict about its function?