Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas, Zacatecas, México.
Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis, San Luis Potosí, San Luis Potosí, México.
PeerJ. 2023 Feb 7;11:e14738. doi: 10.7717/peerj.14738. eCollection 2023.
Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) are chronic degenerative diseases with complex molecular processes that are potentially interconnected. The aim of this work was to predict the potential molecular links between AD and DM2 from different sources of biological information.
In this work, data mining of nine databases (DisGeNET, Ensembl, OMIM, Protein Data Bank, The Human Protein Atlas, UniProt, Gene Expression Omnibus, Human Cell Atlas, and PubMed) was performed to identify gene and protein information that was shared in AD and DM2. Next, the information was mapped to human protein-protein interaction (PPI) networks based on experimental data using the STRING web platform. Then, gene ontology biological process (GOBP) and pathway analyses with EnrichR showed its specific and shared biological process and pathway deregulations. Finally, potential biomarkers and drug targets were predicted with the Metascape platform.
A total of 1,551 genes shared in AD and DM2 were identified. The highest average degree of nodes within the PPI was for DM2 (average = 2.97), followed by AD (average degree = 2.35). GOBP for AD was related to specific transcriptional and translation genetic terms occurring in neurons cells. The GOBP and pathway information for the association AD-DM2 were linked mainly to bioenergetics and cytokine signaling. Within the AD-DM2 association, 10 hub proteins were identified, seven of which were predicted to be present in plasma and exhibit pharmacological interaction with monoclonal antibodies in use, anticancer drugs, and flavonoid derivatives.
Our data mining and analysis strategy showed that there are a plenty of biological information based on experiments that links AD and DM2, which could provide a rational guide to design further diagnosis and treatment for AD and DM2.
阿尔茨海默病(AD)和 2 型糖尿病(DM2)是具有复杂分子过程的慢性退行性疾病,它们可能存在潜在的关联。本研究旨在从不同的生物信息源预测 AD 和 DM2 之间潜在的分子联系。
本研究通过数据挖掘 9 个数据库(DisGeNET、Ensembl、OMIM、蛋白质数据库、人类蛋白质图谱、UniProt、基因表达综合数据库、人类细胞图谱和 PubMed),以识别 AD 和 DM2 中共享的基因和蛋白质信息。接下来,使用 STRING 网络平台,根据实验数据将信息映射到人类蛋白质-蛋白质相互作用(PPI)网络中。然后,EnrichR 进行基因本体生物过程(GOBP)和通路分析,显示其特定和共享的生物过程和通路失调。最后,使用 Metascape 平台预测潜在的生物标志物和药物靶点。
共鉴定出 1551 个在 AD 和 DM2 中共享的基因。PPI 中节点的平均度数最高的是 DM2(平均=2.97),其次是 AD(平均度数=2.35)。AD 的 GOBP 与神经元细胞中发生的特定转录和翻译遗传术语有关。AD-DM2 关联的 GOBP 和途径信息主要与生物能量和细胞因子信号有关。在 AD-DM2 关联中,鉴定出 10 个枢纽蛋白,其中 7 个预测存在于血浆中,并与正在使用的单克隆抗体、抗癌药物和类黄酮衍生物具有药理学相互作用。
我们的数据挖掘和分析策略表明,AD 和 DM2 之间存在大量基于实验的生物学信息,这可为 AD 和 DM2 的进一步诊断和治疗提供合理的指导。