---
title: PPI Network Analysis - Cancer Signaling Pathways
date: 2024-11-18
type: experiment
status: completed
tags: [network-analysis, ppi, cancer, systems-biology]
methods: [Centrality-Measures, Graph-Theory]
related_experiments: [Experiment-2024-11-19]
---

# [[PPI Network Analysis]] - [[Cancer Signaling Pathways]]

## Objective

Map protein-protein interaction network for EGFR signaling pathway. [[Identify]] hub proteins and drug targets.

## Methods

### [[Network Construction]]
- STRING [[Database]] (confidence > 0.7)
- Experimental [[Data]] [[Only]] (co-IP, Y2H)
- 324 proteins, 1,892 interactions

### Centrality Analysis
Applied [[Centrality Measures]] from [[Barabasi2004-Network-Biology]]:
- Degree centrality (connectivity)
- Betweenness centrality (bottlenecks)
- Eigenvector centrality (hub of hubs)

```python
import networkx as nx
G = nx.from_pandas_edgelist(ppi_df)
deg = nx.degree_centrality(G)
bet = nx.betweenness_centrality(G)
eig = nx.eigenvector_centrality(G)
```

### Community Detection
- Louvain algorithm
- Identified 8 functional modules

## Results

### Top Hub Proteins
1. **EGFR** (degree=47, known driver)
2. **GRB2** (degree=38, adapter protein)
3. **SRC** (degree=35, kinase)
4. **PIK3CA** (degree=32, frequently mutated)
5. **MAPK1** (degree=29, downstream effector)

### Bottleneck Proteins (High Betweenness)
- **SHC1** (bridges RTK to MAPK)
- **GAB1** (scaffolding protein)
- **STAT3** (transcription factor)

### Functional Modules
- Module 1: RTK signaling core
- Module 2: MAPK cascade
- Module 3: PI3K/AKT pathway
- Module 4: JAK/STAT pathway

## Discussion

Network topology reveals critical control points. High-betweenness proteins are bottlenecks - potential drug targets.

**Next steps**: [[Experiment-2024-11-19]] will validate hub proteins experimentally.

## Related Work

- Methods from [[Barabasi2004-Network-Biology]]
- Informs [[PPI Network Analysis]] project
- Connected to [[Protein-Interaction-Map]]
- Drug targets feed into [[Drug-Target Prediction]]

## Data Location

`/data/experiments/2024-11-18_EGFR_PPI/`
