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采用综合生物信息学分析鉴定舞蹈棘红细胞增多症中的关键基因和通路。

Identification of pivotal genes and pathways in Chorea-acanthocytosis using comprehensive bioinformatic analysis.

机构信息

Faculty of Pharmaceutical Sciences, The ICFAI University, Baddi, Himachal Pradesh, India.

Department of Clinical Research, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, India.

出版信息

PLoS One. 2024 Sep 18;19(9):e0309594. doi: 10.1371/journal.pone.0309594. eCollection 2024.

DOI:10.1371/journal.pone.0309594
PMID:39292690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11410245/
Abstract

Chorea-acanthocytosis (ChAc), an autosomal recessive disorder, is associated with cognitive and behavioral abnormalities. Previous studies were focused around exploring the functional annotation of VPS13A gene in ChAc, whereas the genetic labyrinth underlying this disease and plausible drug targets were underexplored. In the present study, we have identified the pivotal genes and molecular pathways implicated in ChAc using comprehensive bioinformatics analysis. In our analysis we found 27 distinct genes in Homo sapiens linked to ChAc, out of which 15 were selected as candidate genes for enrichment analysis based on their Gene Ontology (GO) annotations and involvement in relevant molecular pathways. By constructing a Protein-Protein Interaction (PPI) network consisting of 26 nodes and 62 edges, we identified two gene modules. Subsequently, using the MCODE algorithm, we identified 6 hub genes-ATN1, JPH3, TBP, VPS13A, DMD, and HTT-as core candidates. These hub genes are primarily associated with processes such as neuron development and differentiation, the CAMKK-AMPK signaling cascade, ion transmembrane transport systems, and protein localization. Furthermore, using drug gene databank we identified 23 FDA-approved drugs that possess the propensity to target 3 out of the 6 identified hub genes. We believe that our findings could open promising avenues for potential therapeutic interventions in ChAc.

摘要

舞蹈棘红细胞增多症(ChAc)是一种常染色体隐性遗传病,与认知和行为异常有关。以前的研究主要集中在探索 ChAc 中 VPS13A 基因的功能注释上,而该疾病的遗传迷宫和合理的药物靶点则尚未得到充分探索。在本研究中,我们使用综合生物信息学分析方法鉴定了与 ChAc 相关的关键基因和分子途径。在我们的分析中,我们发现了 27 个与 ChAc 相关的不同人类基因,其中 15 个根据其基因本体论(GO)注释和参与相关分子途径被选为富集分析的候选基因。通过构建一个由 26 个节点和 62 个边组成的蛋白质-蛋白质相互作用(PPI)网络,我们鉴定了两个基因模块。随后,使用 MCODE 算法,我们鉴定了 6 个枢纽基因-ATN1、JPH3、TBP、VPS13A、DMD 和 HTT-作为核心候选基因。这些枢纽基因主要与神经元发育和分化、CAMKK-AMPK 信号级联、离子跨膜运输系统和蛋白质定位等过程相关。此外,我们使用药物基因数据库,鉴定出 23 种已获得 FDA 批准的药物,这些药物有可能针对 6 个鉴定出的枢纽基因中的 3 个。我们相信,我们的发现可能为 ChAc 的潜在治疗干预开辟有希望的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f28/11410245/9bd008fd40ac/pone.0309594.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f28/11410245/9bd008fd40ac/pone.0309594.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f28/11410245/1e24a624cd8f/pone.0309594.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f28/11410245/6b722ae748a6/pone.0309594.g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f28/11410245/9bd008fd40ac/pone.0309594.g006.jpg

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