支持寻找放射治疗毒性蛋白质组学特征的数学建模和效应量分析

Kinga Leszczorz, O. Azimzadeh, S. Tapio, M. Atkinson, J. Polańska
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引用次数: 0

摘要

新技术的发展使生物学研究得到了极大的扩展,其中基因组学、转录组学、蛋白质组学和代谢组学的研究处于领先地位。在大多数组学研究中,目标是确定与检测过程相关的可靠分子生物标志物和途径。在几乎所有的情况下,构建一个差异表达基因或蛋白质的列表,这对于一些实验设计来说是不容易获得的。在我们的工作中,我们主要关注小样本量的实验。目的是确定小鼠模型中辐射暴露的强大蛋白质组学特征。我们的选择算法将信号及其折叠变化分布的数学建模与综合效应大小分析相结合。由于数据驱动的蛋白质绝对或相对(折叠变化)表达的自动阈值,以及基于科恩效应大小的过滤器,获得的蛋白质组学特征显示出更高水平的一致性和功能一致性。与标准统计方法相比,确定了额外的,直观预期的信号通路。
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Mathematical Modelling and Effect Size Analysis in Support of Searching for the Proteomic Signature of Radiotherapy Toxicity
Development of new technologies has resulted in the significant expansion of biological research, among which studies in the area of genomics, transcriptomics, proteomics, and metabolomics are the leading ones. In the majority of omics studies, the goal is to identify reliable molecular biomarkers and pathways associated with the examined process. In almost all cases, a list of differentially expressed genes or proteins is constructed, which is not easy to obtain for some experimental designs. In our work, we mainly focus on the experiments with small sample size. The goal was to determine the robust proteomic signature of radiation exposure in the mouse model. Our selection algorithm combines mathematical modelling of signal and its fold change distributions with the comprehensive effect size analysis. Thanks to the data-driven automated thresholding of the protein absolute or relative (fold change) expressions, and Cohens effect size based filters, the obtained proteomic signature demonstrated a higher level of consistency and functional coherency. The additional, intuitively expected, signalling pathways were identified when compared to the standard statistical approach.
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