A novel integrative network approach to understand the interplay between cardiovascular disease and other complex
Deniz Rende1, Nihat Baysal, Betul Kirdar
1Rensselaer Nanotechnology Center, Rensselaer Polytechnic Institute, Troy, NY12180, USA. rended3@rpi.edu
Insights
This study constructed a cardiovascular disease network, revealing functional modules linked to other diseases. It identified potential therapeutic targets and uncovered novel associations between cardiovascular disease and conditions like leprosy and certain cancers.
Area of Science:
- Systems biology
- Bioinformatics
- Genomics
Background:
- Proteins encoded by disease-associated genes often interact and share functions.
- Functional modules within disease networks can reveal links to other complex disorders.
Purpose of the Study:
- To construct a cardiovascular disease functional linkage network (CFN).
- To integrate CFN with bibliomics to identify disease associations and potential therapeutic targets.
Main Methods:
- Construction of a CFN using proteins from 234 cardiovascular disease-associated genes.
- Integration of CFN with bibliomics data.
- Analysis of functional modules and disease associations.
Main Results:
- A CFN with 1536 nodes and 3345 interactions was built.
- 227 out of 566 functional modules were significantly associated with other diseases.
- SP1 and CXCL12 were identified as potential regulatory targets in cardiovascular disease pathogenesis.
- Novel associations were found between cardiovascular disease and leprosy, listeriosis, myasthenia, hemorrhagic diathesis, Protein S deficiency, and epithelial cancers.
Conclusions:
- Integrating functional networks with bibliomics is effective for discovering disease associations.
- SP1 and CXCL12 modulation may offer therapeutic strategies for cardiovascular disease.
- Cardiovascular disease shares complex relationships with various other disorders, including infectious diseases and cancers.
Abstract:
There is accumulating evidence that the proteins encoded by the genes associated with a common disorder interact with each other, participate in similar pathways and share GO terms. It has been anticipated that the functional modules in a disease related functional linkage network can be integrated with bibliomics to reveal association with other complex disorders. In this study, the cardiovascular disease functional linkage network (CFN) containing 1536 nodes and 3345 interactions was constructed using proteins encoded by 234 genes associated with the disease. Integration of CFN with bibliomics showed that 227 out of 566 functional modules are significantly associated with one or more diseases. Analysis of functional modules revealed the possible regulatory roles of SP1 and CXCL12 in the pathogenesis of cardiovascular disease (CVD) and modulation of their activities may be considered as potential therapeutic tools. The integration of CFN with bibliomics also indicated significant relations of CVD with other complex disorders. In a stratified map the members of 227 functional modules and 58 diseases in 15 disease classes were combined. In this map, leprosy, listeria monocytogenes, myasthenia, hemorrhagic diathesis and Protein S deficiency, which were not previously reported to be associated with CVD, showed significant associations. Several cancers arising from epithelial cells were also found to be linked to other diseases through hub proteins, VEGFA and PTGS2.
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