Article thumbnail

Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps

By Ruth Isserlin, Daniele Merico, Rasoul Alikhani-Koupaei, Anthony Gramolini, Gary D Bader and Andrew Emili

Abstract

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

Topics: Research Article
Publisher: WILEY-VCH Verlag
OAI identifier: oai:pubmedcentral.nih.gov:2879143
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2007). Absolute protein expression profiling estimates the relative contributions of transcriptional and translational
  2. (2007). Analyzing the cardiac muscle proteome by liquid chromatography-mass spectrometry-based expression proteomics. Methods Mol. Biol.
  3. (2009). Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling.
  4. (2009). Beta-blocker use for the stages of heart failure. Mayo Clin.
  5. (2005). BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics
  6. (2009). BioMart Central Portal – unified access to biological data. Nucleic Acids Res.
  7. (2003). c-Jun N-terminal kinases (JNK) antagonize cardiac growth through cross-talk with calcineurin-NFAT signaling.
  8. (2008). Canadian Cardiovascular Society Consensus Conference guidelines on heart failure –
  9. (2000). Cardiac remodeling – concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling.
  10. (2006). Cardiovascular proteomics: tools to develop novel biomarkers and potential applications.
  11. (1997). Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science
  12. (2008). Comparative proteomics profiling of a phospholamban mutant mouse model of dilated cardiomyopathy reveals progressive intracellular stress responses.
  13. (2001). Computational analysis of microarray data.
  14. (2007). Control of stress-dependent cardiac growth and gene expression by a microRNA. Science
  15. (2008). CORUM: the comprehensive resource of mammalian protein complexes. Nucleic Acids Res.
  16. (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res.
  17. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol.
  18. (2005). Death begets failure in the heart.
  19. (2000). Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation
  20. (2010). Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.
  21. ErmineJ: tool for functional analysis of gene expression data sets.
  22. (2009). Experimentally observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolism.
  23. (2004). FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes. Bioinformatics
  24. (2009). Formulating and testing hypotheses in functional genomics.
  25. FunSpec: a web-based cluster interpreter for yeast.
  26. (2009). Gelsolin regulates cardiac remodeling after myocardial infarction through DNase I-mediated apoptosis.
  27. (2000). Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
  28. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.
  29. (2007). Global and targeted quantitative proteomics for biomarker discovery.
  30. (2006). Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell
  31. (2008). Heart Disease and Stroke Statistics
  32. (2005). High-Throughput GoMiner, an ‘industrial-strength’ integrative gene ontology tool for interpretation of multiplemicroarray experiments, with application to studies of Common Variable Immune Deficiency (CVID).
  33. (2006). Integrin signalling: the tug-of-war in heart hypertrophy.
  34. (2008). Interpretation of large-scale quantitative shotgun proteomic profiles for biomarker discovery.
  35. Large scale characterization and analysis of the murine cardiac proteome.
  36. (2004). Manipulating cardiac contractility in heart failure: data from mice and men. Circulation
  37. (2007). MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart. Do They Play a Role in Cardiac Hypertrophy?
  38. (2005). Mitochondrial energy metabolism in heart failure: a question of balance.
  39. (2005). Multidimensional protein identification technology (MudPIT): technical overview of a profiling method optimized for the comprehensive proteomic investigation of normal and diseased heart tissue.
  40. (2006). Multiple biomarkers for the prediction of first major cardiovascular events and
  41. (2005). Ontological analysis of gene expression data: current tools, limitations, and open problems. Bioinformatics
  42. (2009). PID: the Pathway Interaction Database. Nucleic Acids Res.
  43. (2007). Predict, prevent and personalize: Genomic and proteomic approaches to cardiovascular
  44. (2009). Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Res.
  45. (2008). Tackling heart failure in the twentyfirst century.
  46. (2003). Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling.
  47. (2007). The bitter end: the ubiquitin-proteasome system and cardiac dysfunction. Circulation
  48. (2007). The failing heart--an engine out of fuel.
  49. (2005). The genetic basis for cardiac remodeling.
  50. (2001). The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy.
  51. (2008). The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res.
  52. (2009). The tail of integrins, talin, and kindlins. Science
  53. (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science