Systems biomedicine of rabies delineates the affected signaling pathways
The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disea...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Frontiers Media
2016
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| _version_ | 1797090758928367616 |
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| author | Azimzadeh Jamalkandi, S Mozhgani, S Gholami Pourbadie, H Mirzaie, M Noorbakhsh, F Vaziri, B Gholami, A Ansari-Pour, N Jafari, M |
| author_facet | Azimzadeh Jamalkandi, S Mozhgani, S Gholami Pourbadie, H Mirzaie, M Noorbakhsh, F Vaziri, B Gholami, A Ansari-Pour, N Jafari, M |
| author_sort | Azimzadeh Jamalkandi, S |
| collection | OXFORD |
| description | The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs) in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein–protein interaction network (PPIN) of infected cells to elucidate the rabies-implicated signal transduction network (RISN). To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets. |
| first_indexed | 2024-03-07T03:23:19Z |
| format | Journal article |
| id | oxford-uuid:b82df6e6-9a77-420b-a8ff-95148dfdc4b6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:23:19Z |
| publishDate | 2016 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:b82df6e6-9a77-420b-a8ff-95148dfdc4b62022-03-27T04:54:08ZSystems biomedicine of rabies delineates the affected signaling pathwaysJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b82df6e6-9a77-420b-a8ff-95148dfdc4b6EnglishSymplectic Elements at OxfordFrontiers Media2016Azimzadeh Jamalkandi, SMozhgani, SGholami Pourbadie, HMirzaie, MNoorbakhsh, FVaziri, BGholami, AAnsari-Pour, NJafari, MThe prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae family that causes lethal encephalomyelitis. Although there have been a plethora of studies investigating the etiological mechanism of the rabies virus and many precautionary methods have been implemented to avert the disease outbreak over the last century, the disease has surprisingly no definite remedy at its late stages. The psychological symptoms and the underlying etiology, as well as the rare survival rate from rabies encephalitis, has still remained a mystery. We, therefore, undertook a systems biomedicine approach to identify the network of gene products implicated in rabies. This was done by meta-analyzing whole-transcriptome microarray datasets of the CNS infected by strain CVS-11, and integrating them with interactome data using computational and statistical methods. We first determined the differentially expressed genes (DEGs) in each study and horizontally integrated the results at the mRNA and microRNA levels separately. A total of 61 seed genes involved in signal propagation system were obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then reconstructed a refined protein–protein interaction network (PPIN) of infected cells to elucidate the rabies-implicated signal transduction network (RISN). To validate our findings, we confirmed differential expression of randomly selected genes in the network using Real-time PCR. In conclusion, the identification of seed genes and their network neighborhood within the refined PPIN can be useful for demonstrating signaling pathways including interferon circumvent, toward proliferation and survival, and neuropathological clue, explaining the intricate underlying molecular neuropathology of rabies infection and thus rendered a molecular framework for predicting potential drug targets. |
| spellingShingle | Azimzadeh Jamalkandi, S Mozhgani, S Gholami Pourbadie, H Mirzaie, M Noorbakhsh, F Vaziri, B Gholami, A Ansari-Pour, N Jafari, M Systems biomedicine of rabies delineates the affected signaling pathways |
| title | Systems biomedicine of rabies delineates the affected signaling pathways |
| title_full | Systems biomedicine of rabies delineates the affected signaling pathways |
| title_fullStr | Systems biomedicine of rabies delineates the affected signaling pathways |
| title_full_unstemmed | Systems biomedicine of rabies delineates the affected signaling pathways |
| title_short | Systems biomedicine of rabies delineates the affected signaling pathways |
| title_sort | systems biomedicine of rabies delineates the affected signaling pathways |
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