转录组-神经影像学研究中的统计检验:评估空间和基因特异性的方法及评估

Statistical testing in transcriptomic-neuroimaging studies: A how-to and evaluation of methods assessing spatial and gene specificity.

机构信息

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

出版信息

Hum Brain Mapp. 2022 Feb 15;43(3):885-901. doi: 10.1002/hbm.25711. Epub 2021 Dec 4.

Abstract

Multiscale integration of gene transcriptomic and neuroimaging data is becoming a widely used approach for exploring the molecular underpinnings of large-scale brain organization in health and disease. Proper statistical evaluation of determined associations between imaging-based phenotypic and transcriptomic data is key in these explorations, in particular to establish whether observed associations exceed "chance level" of random, nonspecific effects. Recent approaches have shown the importance of statistical models that can correct for spatial autocorrelation effects in the data to avoid inflation of reported statistics. Here, we discuss the need for examination of a second category of statistical models in transcriptomic-neuroimaging analyses, namely those that can provide "gene specificity." By means of a couple of simple examples of commonly performed transcriptomic-neuroimaging analyses, we illustrate some of the potentials and challenges of transcriptomic-imaging analyses, showing that providing gene specificity on observed transcriptomic-neuroimaging effects is of high importance to avoid reports of nonspecific effects. Through means of simulations we show that the rate of reported nonspecific effects (i.e., effects that cannot be specifically linked to a specific gene or gene-set) can run as high as 60%, with only less than 5% of transcriptomic-neuroimaging associations observed through ordinary linear regression analyses showing both spatial and gene specificity. We provide a discussion, a tutorial, and an easy-to-use toolbox for the different options of null models in transcriptomic-neuroimaging analyses.

摘要

多尺度整合基因转录组和神经影像学数据正成为探索健康和疾病状态下大规模大脑组织分子基础的一种广泛应用的方法。在这些探索中,对基于成像的表型和转录组数据之间确定的关联进行适当的统计评估是关键,特别是要确定观察到的关联是否超过随机、非特异性效应的“偶然水平”。最近的方法表明,统计模型对于纠正数据中的空间自相关效应以避免报告的统计数据膨胀非常重要。在这里,我们讨论了在转录组-神经影像学分析中需要检查第二类统计模型的必要性,即那些能够提供“基因特异性”的模型。通过对一些常见的转录组-神经影像学分析的简单示例,我们说明了转录组-影像分析的一些潜力和挑战,表明提供观察到的转录组-影像效应的基因特异性对于避免报告非特异性效应非常重要。通过模拟,我们表明报告的非特异性效应(即不能特异性地与特定基因或基因集相关联的效应)的发生率高达 60%,只有不到 5%的通过普通线性回归分析观察到的转录组-神经影像学关联同时具有空间和基因特异性。我们提供了一个讨论、一个教程以及一个用于转录组-神经影像学分析中不同零模型选项的简单易用的工具箱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e57/8764473/9acafebdcbf3/HBM-43-885-g004.jpg

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