Integrative Analysis of Functional Genomic Screening and Clinical Data Identifies a Protective Role for Spironolactone in Severe COVID-19

Cousins, Henry; Kline, Adrienne Sarah; Wang, Chengkun; Qu, Yuanhao; Wang, Mengdi; Altman, Russ B.; Luo, Yunbo; Cong, Le

doi:10.2139/ssrn.4272135

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“…This, in turn, can accelerate the development of targeted therapeutic interventions, precise diagnostic tools, and personalized medicine strategies across a wide range of diseases, including infectious diseases like COVID-19 (11,17). By capitalizing on the capabilities of computational bioinformatics, significant progress can be made in advancing our understanding of biological systems and translating that knowledge into real-world uses that benefit human health and well-being.…”

Section: Functional Genomicsmentioning

confidence: 99%

“…Some of the key applications of functional genomics include identifying novel gene functions and interactions, elucidating disease mechanisms, studying gene regulation and expression, discovering novel biomarkers for disease diagnosis, understanding the impact of environmental factors on gene expression, personalized medicine, and enhancing drug discovery and development (17,(19)(20)(21). By integrating multiple data sets, such as gene expression profiles, protein-protein interaction maps, genetic interaction, and phenotypic data, functional association networks can be generated to reveal the roles of individual genes and their interactions in various biological processes and pathways (Figure 1.2).…”

Section: Applications Of Function Genomicsmentioning

confidence: 99%

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Investigation of Novel Gene Functions in Yeast Using Functional Genomics

Jagadeesan

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Systems biology, a diverse and complex field, relies heavily on functional genomics and highthroughput methods to understand the intricacy of cellular and molecular interactions. Through large-scale, comprehensive genome screening experiments, we generate considerable amounts of data, referred to as "big data," that unravel the complex biochemical interactions within living cells. In this context, Saccharomyces cerevisiae, commonly referred to as baker's yeast serves as a pivotal model organism in scientific research. Its widespread utilization is attributed to the readily available high-throughput techniques, substantial genetic similarity to humans, ease of manipulation, and the wealth of genetic and biochemical resources at its disposal. Our research primarily targets the dissection of the intricate molecular machinery involved in the translation initiation pathway, specifically structured messenger RNAs(mRNAs) in Saccharomyces cerevisiae.Recognizing the centrality of translation to cellular functionality and its perturbation in disease conditions, we employ functional genomic strategies and high-throughput techniques to unearth previously unrecognized gene functions within this process. We examine around 5000 nonessential yeast genes for their effect on the translation of reporter genes, unmasking four previously unidentified gene functions: PEX11, RIM20, YRF1-6, and DBP7. These genes significantly modulate the translation of mRNAs that feature structured 5'UTRs.Further, we leverage a functional genomics computational platform to uncover novel genes implicated in the DNA damage pathway. Integrating protein-protein interactions (PPI), genetic interactions, and gene expression data, we identified three unknown gene functions, GAL7, YMR130W, and YHI9, which are associated with double-strand break repair via both homologous and non-homologous end-joining pathways. These genetic associations are further validated through experimental methodologies. Additionally, we aim to elucidate the inhibitory mechanisms of the SARS-CoV-2 NSP1 gene on translation pathway, proposing the involvement of several other proteins and translation initiation factors critical to viral translation.This research provides profound insights into the complexity of the translation initiation iii pathway, integral to cellular functionality and survival. The revelation of new gene functionalities expands our present understanding and paves the way for further exploration of translational perturbations in disease conditions, thus potentially aiding the development of innovative therapeutic strategies. The integration of large-scale functional genomics and computational strategies enhances our ability to simultaneously evaluate thousands of genes, enriching the depth of our investigations. Also, the investigation of SARS-CoV-2 NSP1 translation inhibitory mechanism using functional genomics approach may expose new targets for antiviral interventions. Given the genetic parallels between baker's yeast and humans, our discoveries could significantly i...

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Section: Functional Genomicsmentioning

confidence: 99%

Section: Applications Of Function Genomicsmentioning

confidence: 99%

Investigation of Novel Gene Functions in Yeast Using Functional Genomics

Jagadeesan

View full text Add to dashboard Cite

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Integrative Analysis of Functional Genomic Screening and Clinical Data Identifies a Protective Role for Spironolactone in Severe COVID-19

Cited by 1 publication

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Investigation of Novel Gene Functions in Yeast Using Functional Genomics

Investigation of Novel Gene Functions in Yeast Using Functional Genomics

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