  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.
