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      • KCI등재

        Computational Identification of Essential Enzymes as Potential Drug Targets in Shigella flexneri Pathogenesis Using Metabolic Pathway Analysis and Epitope Mapping

        ( Priyanka Narad ),( Himanshu ),( Hina Bansal ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.4

        Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen’s essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

      • KCI등재

        Identification of Distinct Vaginal Microbiota Signatures Contributing Toward Preterm Birth Using an Integrative Computational Approach

        Kulshreshtha Sudeepti,Narad Priyanka,Singh Brojen,Modi Deepak,Sengupta Abhishek 한국미생물·생명공학회 2023 한국미생물·생명공학회지 Vol.51 No.1

        Preterm birth (PTB) is defined as giving birth prior to the 37th week of pregnancy and is a major cause of infant mortality. Studies have indicated that the vaginal microbiota's composition and its dysbiosis, particularly during pregnancy, may play a major role in PTB. While previous research work concentrated on well-studied microorganisms such as Lactobacillus, Prevotella, Gardnerella, various other microbes, and their significance in the vaginal microbiota's stability remain unknown. Moreover, current studies have focused primarily on the relative abundances of the microbes found, without considering their interactions with other members of the vaginal microbiota. In this work, we developed a novel computational approach and performed taxonomic classification of vaginal microbiota samples stratified longitudinally (Term/PTB) to observe compositional disparities and find underexamined microbes that may be contributing to PTB. Furthermore, we carried out a correlational analysis to build a microbial co-interaction network and investigated the functional implications of the genes present in both Term and PTB samples. The co-occurrence network revealed that Lactobacillus acts in solidarity to maintain the stability of the vaginal microbiota and did not have strong co-interactions with any of the other microbes. Similarly, microbes with strong interactions with Atopobium, a well-known marker microbe of PTB, were also observed. Additionally, several genes such as PTXA, FANCM, GPX, and DUSP were found to be playing an important role in the occurrence of PTB. This study provides a novel conceptual framework revealing distinct vaginal microbiota signatures that could be potential therapeutic targets for the prevention of PTB.

      • KCI등재

        Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

        ( Richa Buddham ),( Sweety Chauhan ),( Priyanka Narad ),( Puniti Mathur ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.3

        Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

      • KCI등재

        Deciphering Key Genes of Proliferative and Secretory Phase Using Integrated Transcriptomics and Network Analysis

        Gupta Payal,Dube Shriya,Priyadarshini Payal,Singh Shanvi,R Anasuya Pravallika,Srivastava Vijay Lakshmi,Sengupta Abhishek,Narad Priyanka 한국미생물·생명공학회 2023 한국미생물·생명공학회지 Vol.51 No.3

        Endometrium receptivity is a complex mechanism of intricate pathways that lead to the shift from the proliferative to the secretory phase. Our goal was to identify high-ranking differentially expressed genes and study the pathways associated with the phenomenon. Raw data were retrieved from six GEO datasets and 705 DEGs were identified through robust ranking aggregation after the integration of five datasets. 20 key genes were identified that were further re-validated in an additional dataset. Supporting evidence through the experimental references confirms them as major biomarkers of the shift from the proliferative to the secretory phase.

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