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Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder.

ABSTRACT: Prion disorder (PD) is caused by misfolding and the formation of clumps of proteins in the brain, notably Prion proteins resulting in a steady decrease in brain function. Early detection of PD is difficult due to its unpredictable nature, and diagnosis is limited regarding specificity and sensitivity. Considering the uncertainties, the current study used network-based integrative system biology approaches to reveal promising molecular biomarkers and therapeutic targets for PD. In this study, brain transcriptomics gene expression microarray datasets (GSE160208 and GSE124571) of human PD were evaluated and 35 differentially expressed genes (DEGs) were identified. By employing network-based protein-protein interaction (PPI) analysis on these DEGs, 10 central hub proteins, including SPP1, FKBP5, HPRT1, CDKN1A, BAG3, HSPB1, SYK, TNFRSF1A, PTPN6, and CD44, were identified. Employing bioinformatics approaches, a variety of transcription factors (EGR1, SSRP1, POLR2A, TARDP, and NR2F1) and miRNAs (hsa-mir-8485, hsa-mir-148b-3p, hsa-mir-4295, hsa-mir-26b-5p, and hsa-mir-16-5p) were predicted. EGR1 was found as the most imperative transcription factor (TF), and hsa-mir-16-5p and hsa-mir-148b-3p were found as the most crucial miRNAs targeted in PD. Finally, resveratrol and hypochlorous acid were predicted as possible therapeutic drugs for PD. This study could be helpful in better understanding of molecular systems and prospective pharmacological targets for developing effective PD treatments.

SUBMITTER: Mredul MBR

PROVIDER: S-EPMC9793038 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder.

Mredul Md Bazlur Rahman MBR Khan Umama U Rana Humayan Kabir HK Meem Tahera Mahnaz TM Awal Md Abdul MA Rahman Md Habibur MH Khan Md Salauddin MS

Bioinformatics and biology insights 20221224

Prion disorder (PD) is caused by misfolding and the formation of clumps of proteins in the brain, notably Prion proteins resulting in a steady decrease in brain function. Early detection of PD is difficult due to its unpredictable nature, and diagnosis is limited regarding specificity and sensitivity. Considering the uncertainties, the current study used network-based integrative system biology approaches to reveal promising molecular biomarkers and therapeutic targets for PD. In this study, bra ...[more]

PMID: 36582393

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Project description:Although neuropsychiatric (NP) disorders are among the top causes of disability worldwide with enormous financial costs, they can still be viewed as part of the most complex disorders that are of unknown etiology and incomprehensible pathophysiology. The complexity of NP disorders arises from their etiologic heterogeneity and the concurrent influence of environmental and genetic factors. In addition, the absence of rigid boundaries between the normal and diseased state, the remarkable overlap of symptoms among conditions, the high inter-individual and inter-population variations, and the absence of discriminative molecular and/or imaging biomarkers for these diseases makes difficult an accurate diagnosis. Along with the complexity of NP disorders, the practice of psychiatry suffers from a "top-down" method that relied on symptom checklists. Although checklist diagnoses cost less in terms of time and money, they are less accurate than a comprehensive assessment. Thus, reliable and objective diagnostic tools such as biomarkers are needed that can detect and discriminate among NP disorders. The real promise in understanding the pathophysiology of NP disorders lies in bringing back psychiatry to its biological basis in a systemic approach which is needed given the NP disorders' complexity to understand their normal functioning and response to perturbation. This approach is implemented in the systems biology discipline that enables the discovery of disease-specific NP biomarkers for diagnosis and therapeutics. Systems biology involves the use of sophisticated computer software "omics"-based discovery tools and advanced performance computational techniques in order to understand the behavior of biological systems and identify diagnostic and prognostic biomarkers specific for NP disorders together with new targets of therapeutics. In this review, we try to shed light on the need of systems biology, bioinformatics, and biomarkers in neuropsychiatry, and illustrate how the knowledge gained through these methodologies can be translated into clinical use providing clinicians with improved ability to diagnose, manage, and treat NP patients.

Dataset Information

Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder.

Publications

Bioinformatics and System Biology Techniques to Determine Biomolecular Signatures and Pathways of Prion Disorder.

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