## Clustering analysis methods I

In this section we will focus on methods that exclusively use the topology of the network to find closely-connected components. This is generally known in graph theory as 'community detection methods'. No assumptions are made about the internal structure of these communities, we are just looking at high-density regions.

It is important to note that finding the best community structure is algorithmically extremely complex and is only possible for very small networks. For this reason, many approximation methods, often addressing different scenarios, have been developed. There are too many to cover in this course. Some examples include:

- Clique-percolation method
- Markov Clustering Algorithm (MCL)
- Fuzzy C-Means
- Affinity Propagation
- Chinese Whispers Clustering
- Label Propagation Clustering

We will briefly introduce two of the most popular methods used to analyse protein interaction networks: **Newman-Girvan fast greedy algorithm** and the **MCODE algorithm**.

Another way to address the search for communities within a network is to use a combination of the topology of the network and some external property, such as protein expression values, as an additional layer defining communities. A good example of this popular method is the jActiveModules app for Cytoscape (17). This app “[…] searches a molecular interaction network to find expression activated sub-networks. Such sub-networks are connected regions of a network that show significant changes in expression over particular subsets of conditions” (18). In essence, connected regions within a network with differential expression can be identified using this tool.