Maricel G. Kann | Searcharxiv

arXiv2019

DomainScope: A disease network based on protein domain connections

Protein domains are highly conserved functional units of proteins. Because they carry functionally significant information, the majority of the coding disease variants are located on domains. Additionally, domains are specific units of the proteins that can be targeted for drug delivery purposes. Here, using information about variants sites associated with diseases, a disease network was built, based on their sharing the same domain and domain variation site. The result was 49,990 disease pairs linked by domain variant site and 533,687 disease pairs that share the same mutated domain. These pairs were compared to disease pairs made using previous methods such as gene identity and gene variant site identity, which revealed that over 8,000 of these pairs were not only missing from the gene pairings but also not found commonly together in literature. The disease network was analyzed from their disease subject categories, which when compared to the gene-based disease network revealed that the domain method results in higher number of connections across disease categories versus within a disease category. Further, a study into the drug repurposing possibilities of the disease network created using domain revealed that 16,902 of the disease pairs had a drug reported for one disease but not the other, highlighting the drug repurposing potential of this new methodology.

q-bio.GN↗

arXiv2006

Transcriptional Interactions During Smallpox Infection and Identification of Early Infection Biomarkers

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.

q-bio.MN↗