Disentangling function from topology to infer the network properties of disease genes

BMC Systems Biology

Mona Singh²  Dario Ghersi¹ 

[1] Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA;Department of Computer Science, Princeton University, Princeton, NJ 08540, USA

关键词: Gene ontology;    Functional bias;    Networks;    Disease genes;   

Others  :  1143228
DOI  :  10.1186/1752-0509-7-5

 received in 2012-10-22, accepted in 2013-01-04,  发布年份 2013

【 摘 要 】

Background

The topological features of disease genes within interaction networks are the subject of intense study, as they shed light on common mechanisms of pathology and are useful for uncovering additional disease genes. Computational analyses typically try to uncover whether disease genes exhibit distinct network features, as compared to all genes.

Results

We demonstrate that the functional composition of disease gene sets is an important confounding factor in these types of analyses. We consider five disease sets and show that while they indeed have distinct topological features, they are also enriched in functions that a priori exhibit distinct network properties. To address this, we develop a computational framework to assess the network properties of disease genes based on a sampling algorithm that generates control gene sets that are functionally similar to the disease set. Using our function-constrained sampling approach, we demonstrate that for most of the topological properties studied, disease genes are more similar to sets of genes with similar functional make-up than they are to randomly selected genes; this suggests that these observed differences in topological properties reflect not only the distinguishing network features of disease genes but also their functional composition. Nevertheless, we also highlight many cases where disease genes have distinct topological properties even when accounting for function.

Conclusions

Our approach is an important first step in extracting the residual topological differences in disease genes when accounting for function, and leads to new insights into the network properties of disease genes.

【 授权许可】

   
2013 Ghersi and Singh; licensee BioMed Central Ltd.

【 图 表 】

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