Search bioRxiv⌕ Search

Biology subjects

Wani, S. A.

Publications and source records attributed to Wani, S. A..

2 recordsLinked to original sources
bioRxiv2020

Systems Biology behind immunoprotection of both Sheep and Goats after Sungri/96 PPRV vaccination

Immune response is a highly coordinated cascade involving all the subsets of PBMCs. In this study, RNA-Seq analysis of PBMC subsets - CD4+, CD8+, CD14+, CD21+ and CD335+ cells from day 0 and day 5 of Sungri/96 Peste des Petits Ruminants vaccinated sheep and goats was done to delineate the systems biology behind immune - protection of the vaccine in sheep and goats. Assessment of the immune response processes enriched by the differentially expressed genes in all the subsets suggested a strong dysregulation towards development of early inflammatory microenvironment, which is very much required for differentiation of monocytes to macrophages, and for activation and migration of dendritic cells into the draining lymph nodes. The protein - protein interaction networks among the antiviral molecules (IFIT3, ISG15, MX1, MX2, RSAD2, ISG20, IFIT5 and IFIT1) and common DEGs across PBMCs subsets in both the species identified ISG15 to be an ubiquitous hub, that helps in orchestrating antiviral host response against PPRV. IRF7 was found to be the key master regulator activated in most of the subsets in sheep and goats. Most of the pathways were found to be inactivated in B - lymphocytes of both the species indicating that 5 dpv is too early a time point for the B - lymphocytes to react. The cell mediated immune response and humoral immune response pathways were found more enriched in goats than in sheep. Though, animals from both the species survived the challenge, a contrast in pathway activation was observed in CD335+ cells. ImportancePeste des petits ruminants (PPR) by PPRV is an OIE listed acute, contagious transboundary viral disease of small ruminants. Attenuated Sungri/96 PPRV vaccine used all over India against this PPR, provides long-lasting robust innate and adaptive immune response. The early antiviral response was found mediated through type I interferon independent ISGs expression. However, systems biology behind this immune response is unknown. In this study, in vivo transcriptome profiling of PBMC subsets (CD4+, CD8+, CD14+, CD21+ and CD335+) in vaccinated goats and sheep (at 5 days of post vaccination) was done to understand this systems biology. Though there are a few differences in the systems biology across cells (specially the NK cells) between sheep and goats, the co-ordinated response that is inclusive of all the cell subsets was found to be towards induction of strong innate immune response, which is needed for an appropriate adaptive immune response.

systems biology↗
bioRxiv2020

Genome-wide analyses of transcription factors and co-regulators across seven cohorts identified reduced PPARGC1A expression as a driver of prostate cancer progression

Defining altered transcription factor (TF) and coregulators that are oncogenic drivers remains a challenge, in part because of the multitude of TFs and coregulators. We addressed this challenge by using bootstrap approaches to test how expression, copy number alterations or mutation of TFs (n = 2662), coactivators (COA; n= 766); corepressor (COR; n = 599); mixed function coregulators (MIXED; n = 511) varied across seven prostate cancer (PCa) cohorts (three of localized and four advanced disease). COAS, CORS, MIXED and TFs all displayed significant down-regulated expression (q.value < 0.1) and correlated with protein expression ({rho} 0.4 to 0.55). Stringent expression filtering identified commonly altered TFs and coregulators including well-established (e.g. ERG) and underexplored (e.g. PPARGC1A, encodes PGC1) in localized PCa. Reduced PPARGC1A expression significantly associated with worse disease-free survival in two cohorts of localized PCa. Stable PGC1 knockdown in LNCaP cells increased growth rates and invasiveness and RNA-Seq revealed a profound basal impact on gene expression (~2300 genes; FDR < 0.05, logFC > 1.5), but only modestly impacted PPAR{gamma} responses. GSEA analyses of the PGC1 transcriptome revealed that it significantly altered the AR-dependent transcriptome, and was enriched for epigenetic modifiers. PGC1-dependent genes were overlapped with PGC1-ChIP-Seq genes and significantly associated in TCGA with higher grade tumors and worse disease-free survival. Together these data demonstrate an approach to identify cancer-driver coregulators in cancer and that PGC1 expression is clinically significant yet underexplored coregulator in aggressive early stage PCa.

cancer biology↗