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10.1101/2021.05.31.21254851 http://scihub22266oqcxt.onion/10.1101/2021.05.31.21254851 34100031!8183086!34100031     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       medRxiv 2021 ; ä (ä): ä Nephropedia Template TP {{tp|p=34100031|t=2021. IL10RB as a key regulator of COVID-19 host susceptibility and severity |pdf=|usr=}}{{34100031}} gab.com Text IL10RB as a key regulator of COVID-19 host susceptibility and severity JO: medRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34100031 #FOAvip BACKGROUND: Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step. METHODS: We integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility. The top candidate gene is validated by testing both its GReX and observed blood transcriptome association with COVID-19 severity, as well as by in vitro perturbation to quantify effects on viral load and molecular pathway dysregulation. We validate the in silico drug repositioning analysis by examining whether the top candidate compounds decrease COVID-19 incidence based on epidemiological evidence. RESULTS: We identify IL10RB as the top key regulator of COVID-19 host susceptibility. Predicted GReX up-regulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes. In vitro IL10RB overexpression is associated with increased viral load and activation of immune-related molecular pathways. Azathioprine and retinol are prioritized as candidate compounds to reduce the likelihood of testing positive for COVID-19. CONCLUSIONS: We establish an integrative data-driven approach for gene target prioritization. We identify and validate IL10RB as a suitable molecular target for modulation of COVID-19 host susceptibility. Finally, we provide evidence for a few readily available medications that would warrant further investigation as drug repositioning candidates. Twit Text FOAVip IL10RB as a key regulator of COVID-19 host susceptibility and severity ????medRxiv http://www.kidney.de/pget.php?&tw=1&pmid=34100031 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34100031 #FOAvip English Wikipedia <ref>{{Cite pmid|34100031}}</ref> IL10RB as a key regulator of COVID-19 host susceptibility and severity #MMPMID34100031 Voloudakis G; Hoffman G; Venkatesh S; Lee KM; Dobrindt K; Vicari JM; Zhang W; Beckmann ND; Jiang S; Hoagland D; Bian J; Gao L; Corvelo A; Cho K; Lee JS; Iyengar SK; Luoh SW; Akbarian S; Striker R; Assimes TL; Schadt EE; Merad M; tenOever BR; Charney AW; Brennand KJ; Lynch JA; Fullard JF; Roussos P medRxiv 2021[Jun]; ä (ä): ä PMID34100031show ga BACKGROUND: Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step. METHODS: We integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility. The top candidate gene is validated by testing both its GReX and observed blood transcriptome association with COVID-19 severity, as well as by in vitro perturbation to quantify effects on viral load and molecular pathway dysregulation. We validate the in silico drug repositioning analysis by examining whether the top candidate compounds decrease COVID-19 incidence based on epidemiological evidence. RESULTS: We identify IL10RB as the top key regulator of COVID-19 host susceptibility. Predicted GReX up-regulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes. In vitro IL10RB overexpression is associated with increased viral load and activation of immune-related molecular pathways. Azathioprine and retinol are prioritized as candidate compounds to reduce the likelihood of testing positive for COVID-19. CONCLUSIONS: We establish an integrative data-driven approach for gene target prioritization. We identify and validate IL10RB as a suitable molecular target for modulation of COVID-19 host susceptibility. Finally, we provide evidence for a few readily available medications that would warrant further investigation as drug repositioning candidates. äIL10RB as a key regulator of COVID-19 host susceptibility and severity(epmc).pdf DeepDyve Pubget Overpricing