dorsal/arxiv
View SchemaTranscriptional Interactions During Smallpox Infection and Identification of Early Infection Biomarkers
| Authors | Willy A. Valdivia-Granda, Maricel G. Kann, Jose Malaga |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0610023 |
| URL | https://arxiv.org/abs/q-bio/0610023 |
| Journal | Pacific Symposium on Biocomputing (2007) |
Abstract
Smallpox is a deadly disease that can be intentionally reintroduced into the human population as a bioweapon. While host gene expression microarray profiling can be used to detect infection, the analysis of this information using unsupervised and supervised classification techniques can produce contradictory results. Here, we present a novel computational approach to incorporate molecular genome annotation features that are key for identifying early infection biomarkers (EIB). Our analysis identified 58 EIBs expressed in peripheral blood mononuclear cells (PBMCs) collected from 21 cynomolgus macaques (Macaca fascicularis) infected with two variola strains via aerosol and intravenous exposure. The level of expression of these EIBs was correlated with disease progression and severity. No overlap between the EIBs co-expression and protein interaction data reported in public databases was found. This suggests that a pathogen-specific re-organization of the gene expression and protein interaction networks occurs during infection. To identify potential genome-wide protein interactions between variola and humans, we performed a protein domain analysis of all smallpox and human proteins. We found that only 55 of the 161 protein domains in smallpox are also present in the human genome. These co-occurring domains are mostly represented in proteins involved in blood coagulation, complement activation, angiogenesis, inflammation, and hormone transport. Several of these proteins are within the EIBs category and suggest potential new targets for the development of therapeutic countermeasures.
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"abstract": "Smallpox is a deadly disease that can be intentionally reintroduced into the\nhuman population as a bioweapon. While host gene expression microarray\nprofiling can be used to detect infection, the analysis of this information\nusing unsupervised and supervised classification techniques can produce\ncontradictory results. Here, we present a novel computational approach to\nincorporate molecular genome annotation features that are key for identifying\nearly infection biomarkers (EIB). Our analysis identified 58 EIBs expressed in\nperipheral blood mononuclear cells (PBMCs) collected from 21 cynomolgus\nmacaques (Macaca fascicularis) infected with two variola strains via aerosol\nand intravenous exposure. The level of expression of these EIBs was correlated\nwith disease progression and severity. No overlap between the EIBs\nco-expression and protein interaction data reported in public databases was\nfound. This suggests that a pathogen-specific re-organization of the gene\nexpression and protein interaction networks occurs during infection. To\nidentify potential genome-wide protein interactions between variola and humans,\nwe performed a protein domain analysis of all smallpox and human proteins. We\nfound that only 55 of the 161 protein domains in smallpox are also present in\nthe human genome. These co-occurring domains are mostly represented in proteins\ninvolved in blood coagulation, complement activation, angiogenesis,\ninflammation, and hormone transport. Several of these proteins are within the\nEIBs category and suggest potential new targets for the development of\ntherapeutic countermeasures.",
"arxiv_id": "q-bio/0610023",
"authors": [
"Willy A. Valdivia-Granda",
"Maricel G. Kann",
"Jose Malaga"
],
"categories": [
"q-bio.MN",
"q-bio.GN"
],
"journal_ref": "Pacific Symposium on Biocomputing (2007)",
"title": "Transcriptional Interactions During Smallpox Infection and Identification of Early Infection Biomarkers",
"url": "https://arxiv.org/abs/q-bio/0610023"
},
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