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Molecular Architecture of Spinal Cord Injury Protein Interaction Network.

Alawieh A, Sabra M, Sabra Z, Tomlinson S, Zaraket FA - PLoS ONE (2015)

Bottom Line: Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI.In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy.Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Institute, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.

ABSTRACT
Spinal cord injury (SCI) is associated with complex pathophysiological processes that follow the primary traumatic event and determine the extent of secondary damage and functional recovery. Numerous reports have used global and hypothesis-driven approaches to identify protein changes that contribute to the overall pathology of SCI in an effort to identify potential therapeutic interventions. In this study, we use a semi-automatic annotation approach to detect terms referring to genes or proteins dysregulated in the SCI literature and develop a curated SCI interactome. Network analysis of the SCI interactome revealed the presence of a rich-club organization corresponding to a "powerhouse" of highly interacting hub-proteins. Studying the modular organization of the network have shown that rich-club proteins cluster into modules that are specifically enriched for biological processes that fall under the categories of cell death, inflammation, injury recognition and systems development. Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI. In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy. Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.

No MeSH data available.


Related in: MedlinePlus

Functional annotation of the SCI meta-proteome.Enriched GO cellular components (A), GO biological processes (B), and KEGG pathways (C). Terms restricted to most significantly enriched terms (p-value <1E-10). For clarity of presentation, enrichment scores were reported as log (1/p-value). Full list of DAVID enrichment analysis is available in S4, S5 and S6 Tables.
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pone.0135024.g002: Functional annotation of the SCI meta-proteome.Enriched GO cellular components (A), GO biological processes (B), and KEGG pathways (C). Terms restricted to most significantly enriched terms (p-value <1E-10). For clarity of presentation, enrichment scores were reported as log (1/p-value). Full list of DAVID enrichment analysis is available in S4, S5 and S6 Tables.

Mentions: Functional annotation of the SCI meta-proteome was performed to provide a global overview of the pathophysiological processes and pathways over-represented in the SCI meta-proteome (Fig 2). Gene Ontology analysis [7,8] showed significant overrepresentation of proteins located in the extracellular, plasma membrane and neuronal compartments (Fig 2a), as well as those involved in response to wounding and organic stimulus, cellular death and proliferation, and cell-cell signaling (Fig 2b). We also analyzed biological and disease pathway enrichment using the KEGG database. The top enriched pathways fell into four major categories: 1. Growth factor signaling pathways, 2. Apoptotic and cell death pathways, 3. Inflammatory and immune pathways and, 4. Developmental pathways and calcium signaling pathway (Fig 2c). These findings fit with our current understanding of SCI injury, hallmarks of which include apoptosis and cell death, immune system activation and calcium signaling [4,20].


Molecular Architecture of Spinal Cord Injury Protein Interaction Network.

Alawieh A, Sabra M, Sabra Z, Tomlinson S, Zaraket FA - PLoS ONE (2015)

Functional annotation of the SCI meta-proteome.Enriched GO cellular components (A), GO biological processes (B), and KEGG pathways (C). Terms restricted to most significantly enriched terms (p-value <1E-10). For clarity of presentation, enrichment scores were reported as log (1/p-value). Full list of DAVID enrichment analysis is available in S4, S5 and S6 Tables.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524728&req=5

pone.0135024.g002: Functional annotation of the SCI meta-proteome.Enriched GO cellular components (A), GO biological processes (B), and KEGG pathways (C). Terms restricted to most significantly enriched terms (p-value <1E-10). For clarity of presentation, enrichment scores were reported as log (1/p-value). Full list of DAVID enrichment analysis is available in S4, S5 and S6 Tables.
Mentions: Functional annotation of the SCI meta-proteome was performed to provide a global overview of the pathophysiological processes and pathways over-represented in the SCI meta-proteome (Fig 2). Gene Ontology analysis [7,8] showed significant overrepresentation of proteins located in the extracellular, plasma membrane and neuronal compartments (Fig 2a), as well as those involved in response to wounding and organic stimulus, cellular death and proliferation, and cell-cell signaling (Fig 2b). We also analyzed biological and disease pathway enrichment using the KEGG database. The top enriched pathways fell into four major categories: 1. Growth factor signaling pathways, 2. Apoptotic and cell death pathways, 3. Inflammatory and immune pathways and, 4. Developmental pathways and calcium signaling pathway (Fig 2c). These findings fit with our current understanding of SCI injury, hallmarks of which include apoptosis and cell death, immune system activation and calcium signaling [4,20].

Bottom Line: Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI.In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy.Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Institute, Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, United States of America; Department of Electrical and Computer Engineering, American University of Beirut, Beirut, Lebanon.

ABSTRACT
Spinal cord injury (SCI) is associated with complex pathophysiological processes that follow the primary traumatic event and determine the extent of secondary damage and functional recovery. Numerous reports have used global and hypothesis-driven approaches to identify protein changes that contribute to the overall pathology of SCI in an effort to identify potential therapeutic interventions. In this study, we use a semi-automatic annotation approach to detect terms referring to genes or proteins dysregulated in the SCI literature and develop a curated SCI interactome. Network analysis of the SCI interactome revealed the presence of a rich-club organization corresponding to a "powerhouse" of highly interacting hub-proteins. Studying the modular organization of the network have shown that rich-club proteins cluster into modules that are specifically enriched for biological processes that fall under the categories of cell death, inflammation, injury recognition and systems development. Pathway analysis of the interactome and the rich-club revealed high similarity indicating the role of the rich-club proteins as hubs of the most prominent pathways in disease pathophysiology and illustrating the centrality of pro-and anti-survival signal competition in the pathology of SCI. In addition, evaluation of centrality measures of single nodes within the rich-club have revealed that neuronal growth factor (NGF), caspase 3, and H-Ras are the most central nodes and potentially an interesting targets for therapy. Our integrative approach uncovers the molecular architecture of SCI interactome, and provide an essential resource for evaluating significant therapeutic candidates.

No MeSH data available.


Related in: MedlinePlus