Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
Front Endocrinol (Lausanne). 2023 Jan 19;13:1084656. doi: 10.3389/fendo.2022.1084656. eCollection 2022.
MicroRNAs (miRNAs) are critical regulators of gene expression in healthy and diseased states, and numerous studies have established their tremendous potential as a tool for improving the diagnosis of Type 2 Diabetes Mellitus (T2D) and its comorbidities. In this regard, we computationally identify novel top-ranked hub miRNAs that might be involved in T2D. We accomplish this two strategies: 1) by ranking miRNAs based on the number of T2D differentially expressed genes (DEGs) they target, and 2) using only the common DEGs between T2D and its comorbidity, Alzheimer's disease (AD) to predict and rank miRNA. Then classifier models are built using the DEGs targeted by each miRNA as features. Here, we show the T2D DEGs targeted by hsa-mir-1-3p, hsa-mir-16-5p, hsa-mir-124-3p, hsa-mir-34a-5p, hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-129-2-3p, and hsa-mir-146a-5p are capable of distinguishing T2D samples from the controls, which serves as a measure of confidence in the miRNAs' potential role in T2D progression. Moreover, for the second strategy, we show other critical miRNAs can be made apparent through the disease's comorbidities, and in this case, overall, the hsa-mir-103a-3p models work well for all the datasets, especially in T2D, while the hsa-mir-124-3p models achieved the best scores for the AD datasets. To the best of our knowledge, this is the first study that used predicted miRNAs to determine the features that can separate the diseased samples (T2D or AD) from the normal ones, instead of using conventional non-biology-based feature selection methods.
微小 RNA(miRNA)是健康和疾病状态下基因表达的关键调节剂,许多研究已经证实,miRNA 具有巨大的潜力,可以作为改善 2 型糖尿病(T2D)及其合并症诊断的工具。在这方面,我们通过计算方法识别可能与 T2D 相关的新型顶级枢纽 miRNA。我们通过两种策略来实现这一目标:1)根据 miRNA 靶向的 T2D 差异表达基因(DEG)数量对 miRNA 进行排名,2)仅使用 T2D 与其合并症阿尔茨海默病(AD)之间的共同 DEG 来预测和排名 miRNA。然后,使用每个 miRNA 靶向的 DEG 作为特征构建分类器模型。在这里,我们展示了 hsa-mir-1-3p、hsa-mir-16-5p、hsa-mir-124-3p、hsa-mir-34a-5p、hsa-let-7b-5p、hsa-mir-155-5p、hsa-mir-107、hsa-mir-27a-3p、hsa-mir-129-2-3p 和 hsa-mir-146a-5p 靶向的 T2D DEG 能够区分 T2D 样本与对照,这是 miRNA 在 T2D 进展中潜在作用的置信度的衡量标准。此外,对于第二种策略,我们通过疾病的合并症可以发现其他关键的 miRNA,在这种情况下,总体而言,hsa-mir-103a-3p 模型在所有数据集上都表现良好,尤其是在 T2D 中,而 hsa-mir-124-3p 模型在 AD 数据集上的得分最高。据我们所知,这是第一项使用预测 miRNA 来确定可以将患病样本(T2D 或 AD)与正常样本区分开来的特征的研究,而不是使用传统的非基于生物学的特征选择方法。
Front Endocrinol (Lausanne). 2022
Mol Neurobiol. 2019-6-25
Acta Neuropathol Commun. 2017-1-31
Front Immunol. 2025-8-14
Front Endocrinol (Lausanne). 2025-6-12
Sensors (Basel). 2024-8-19
Curr Protoc. 2021-3
Methods Protoc. 2020-12-24
Nucleic Acids Res. 2020-7-2