Transcriptomics-Based Computational Drug Repurposing Strategy For Identified Therapeutic Candidates Tuberculosis meningitis

Tuberculous meningitis is a devastating disease of the central nervous system. This diseasemainly affects the meninges of the brain and spinal cord along with the adjacent brain parenchyma.Early diagnosis is important for successful treatment (۱). Drug repurposing is a valuable alternativeapproach to discover new indications for approved or investigational drugs beyond their originalindication (۲). RNA sequencing (RNA-seq) is one of the effective methods to find the heterogeneousgene expression of diseases in response to certain drugs (۳). Therefore, our study used a computationaldrug repurposing pipeline to discover candidate drugs by PD differential gene expression signaturesderived from RNA sequencing data. The transcriptional profile of whole blood in children with andwithout tuberculous meningitis (TBM) was compared, under the accession code GSE۱۱۱۴۵۹ wereobtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). A total of ۴۳ whole bloodsamples including ۱۵ TBM cases and ۲۴ uninfected healthy individuals were sequenced (۴).Differentially expressed genes (DEGs) between blood samples of people with tuberculous meningitisand blood samples of healthy and non-infected people were obtained using GEO۲R. Then, the Libraryof Integrated Network-Based Signatures (LINCS) database was used to identify potential drugs that canreverse the expression of DEGs. Then, by reviewing the significant literature and Drug bank studies(https://go.drugbank.com), the top-ranked drugs with the highest p-value were selected. This studyidentified ۲۵۲ genes that were generally affected by the disease, among which genes with |log۲FC| >۱and P-value <۰.۰۵ were identified as DEGs: ۱۰۹ up-regulated genes and ۱۴۳ down-regulated genes.Lisofylline (LSF) is a synthetic small molecule with novel anti-inflammatory properties. LSF caneffectively prevent type ۱ diabetes in clinical models and improve the function and survival of isolatedor transplanted pancreatic islets (۵).

کلیدواژه ها:

RNA sequencing ، Tuberculous meningitis ، Drug repurposing