Functional Annotation vs Functional Enrichment--which one should I use for Network Analysis?
The answer to your main doubt about &quot;annotation vs. enrichment&quot; is that you need both, but you already have one annotation.
You can only perform a functional enrichment analysis after you have a functional annotation. In your question, you state that you have KEGG annotation for your targets. That is it, knowing which target &quot;belongs&quot; to each KEGG module is an example of functional annotation of your targets. Several tools can annotate genes, proteins, etc. Knowing which protein is related to each drug or disease is also a functional annotation.
Now, knowing which targets are significantly important can be achieved by functional enrichment analysis.
For the network, both information can be used together. For example, you could link all elements to their functional annotation and use the available enrichment score as a quantitative parameter of importance for calculating correlations.