Biologically Relevant Heterogeneity: Metrics and Practical Insights.
Biologically Relevant Heterogeneity: Metrics and Practical Insights.
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DOI：
10.1177/2472555216682725
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Taylor DL
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文献类型：
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作者：
Gough A;Stern AM;Maier J;Lezon T;Shun TY;Chennubhotla C;Schurdak ME;Haney SA;Taylor DL
异质性是所有尺度生物系统的基本属性，必须在广泛的生物医学应用中解决，包括基础生物医学研究、药物发现、诊断和精准医学的实施。有许多已发表的方法来表征体外细胞和组织切片中的异质性。然而，不存在可应用于相对高通量工作流程的用于异质性的检测和定量的普遍接受的方法。这篇综述和展望强调了捕获多路复用细胞水平数据的实验方法，以及对异质性的空间、时间和人口组成部分的标准度量的需要。建议采用一组三个异质性指数，可以实现在任何高吞吐量的工作流程，以优化决策过程。此外，成对互信息的方法，建议作为一种方法来表征异质性的空间特征，特别是在基于组织的成像。此外，时间异质性的度量还处于发展的早期阶段。实例研究表明，功能表型异质性的分析可以用来指导决策的解释生物医学实验，药物发现，诊断和设计的最佳治疗策略，为个别患者。
Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications including basic biomedical research, drug discovery, diagnostics and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high throughput workflow. This review and perspective emphasizes the experimental methods that capture multiplexed cell level data, as well as the need for standard metrics of the spatial, temporal and population components of heterogeneity. A recommendation is made for the adoption of a set of three heterogeneity indices that can be implemented in any high throughput workflow to optimize the decision-making process. In addition, a pairwise mutual information method is suggested as an approach to characterizing the spatial features of heterogeneity, especially in tissue-based imaging. Furthermore, metrics for temporal heterogeneity are in the early stages of development. Example studies indicate that the analysis of functional phenotypic heterogeneity can be exploited to guide decisions in the interpretation of biomedical experiments, drug discovery, diagnostics and the design of optimal therapeutic strategies for individual patients.