Tips for Interpreting Gene or Protein Interaction Networks

Interpreting gene or protein interaction networks is an invaluable skill in biomedical research. Effective interpretation of networks results in the discovery of biological mechanisms that describe the behavior of a research model (cell line, genetically modified organism, tumor, etc.) and guides future experiments. This book offers 18 tips that will help the novice and the veteran researcher interpret high-throughput omics data.

Excerpt:

Tip #1. Things may not be what they seem.
The most important piece of advice that I can give about interpreting gene networks is that things may not be what they seem; meaning the biological processes that are enriched in your gene list of interest may not be what is actually happening in your research model. If you are studying gene expression of a tissue that does not have skeletal muscle, but receive “muscle development” as an enriched category, it wasn’t a mistake. Epithelial cells can undergo epithelial-to-mesenchymal transition (EMT) during which they up-regulate genes such as smooth muscle actin. Thus, muscle development may actually be EMT.

Here are other hypothetical examples of hidden meanings.

“Organismal development” may be metastasis. The process of organismal development involves the movement of cells to different compartments and then differentiation into mature cell types. This differentiation process can involve the expression of genes that form cell-cell junctions and cell-matrix connections. These same processes are down-regulated during metastasis.

Other tips:
Tip #7. Don't be overly swayed by fold-changes, big or small.
Tip #14. Cell culture, organ culture, organism, or colony?
Tip #15. Use network analysis to predict targets for, or guide, biochemistry assays.