Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps
Open accessAbstract
Global protein expression profiling can potentially uncover perturbations associated with common forms of heart disease. We have used shotgun MS/MS to monitor the state of biological systems in cardiac tissue correlating with disease onset, cardiac insufficiency and progression to heart failure in a time‐course mouse model of dilated cardiomyopathy. However, interpreting the functional significance of the hundreds of differentially expressed proteins has been challenging. Here, we utilize improved enrichment statistical methods and an extensive collection of functionally related gene sets, gaining a more comprehensive understanding of the progressive alterations associated with functional decline in dilated cardiomyopathy. We visualize the enrichment results as an Enrichment Map, where significant gene sets are grouped based on annotation similarity. This approach vastly simplifies the interpretation of the large number of enriched gene sets found. For pathways of specific interest, such as Apoptosis and the MAPK (mitogen‐activated protein kinase) cascade, we performed a more detailed analysis of the underlying signaling network, including experimental validation of expression patterns.
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Protein expression data combined with pathway information highlighted the importance of apoptosis in a mouse model of heart disease.
“For instance, protein expression data was combined with pathway information to highlight the importance of apoptosis in a mouse model of heart disease50.”
From The BioPAX community standard for pathway data sharing (2010) · cites this paper as [50]
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- Authors
- Isserlin, R., Merico, D., Alikhani‐Koupaei, R., Gramolini, A., Bader, G. D., & Emili, A.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Emili, Andrew
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 10
- Issue
- 6
- Pages
- 1316-1327
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- PMC
- PMC2879143
- OpenAlex
- W2038651305
- Cited by
- 63
- References
- 57
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 8
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- PROTEOMICS (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- US NIH via National Human Genome Research Institute (P41 P41HG04118)
- Canada Foundation for Innovation
- Ontario Research Fund
- Heart and Stroke Foundation of Ontario, the ORF, and Genome Canada via the Ontario Genomics Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- dilated cardiomyopathy, cardiac proteome, protein expression profiling, heart failure, gene set enrichment analysis, apoptosis, MAPK signaling, signaling networks, mouse model, disease progression
- MeSH terms
- Animals, Cardiomyopathy, Dilated, Propranolol, Apoptosis, Gelsolin, Gene Expression Profiling, MAP Kinase Signaling System, Databases, Protein, Proteomics, Systems Biology, Mice, Caspase 3, Tandem Mass Spectrometry, Metabolomics
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