RchyOptimyx: Cellular hierarchy optimization for flow cytometry

RchyOptimyx: Cellular hierarchy optimization for flow cytometry
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DOI:
10.1002/cyto.a.22209
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发表时间:
2012-12-01
期刊:
影响因子:
3.7
通讯作者:
Brinkman, Ryan R.
Brinkman, Ryan R.
中科院分区:
生物学4区
文献类型:
--
作者:
Aghaeepour, Nima;Jalali, Adrin;Brinkman, Ryan R.

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对高维流式细胞仪数据集的分析可以揭示出知识生物学知识的新细胞群体。在发现之后,根据所涉及的关键标记来表征这些人群是一个重要的一步,因为这可以帮助更好地了解这些人群的生物学,并有助于设计更简单的标记面板,以在更简单的仪器上识别它们,并且更少的试剂(较少的试剂)(即,在资源贫困或高度调节的临床环境中)。但是,根据目标细胞群体的生物学特征设计面板的当前工具专门根据技术参数(例如仪器配置,光谱重叠和试剂可用性)来工作。为了解决这一缺点,我们开发了Rchyoptimyx(蜂窝层次结构优化),这是一种计算工具,通过将自动化的门控与动态编程和图形理论相结合来构建细胞层次结构,以提供最佳的门控策略,以确定目标人群到所需的纯度或相关性水平或相关性水平使用临床结果,使用最简单的标记面板。 Rchyoptimyx可以评估并以图形方式介绍高维流量或质量细胞仪数据集中标记选择和人口特异性之间的权衡。我们提出了三种概念验证案例,涉及Rchyoptimyx,其中涉及1)设计一组表面标记,以识别主要使用其细胞内特征表征的稀有种群; 2)简化识别目标细胞群体的门控策略; 3)鉴定非冗余标记以识别目标细胞群体。 (c)2012年国际细胞仪协会
Analysis of high-dimensional flow cytometry datasets can reveal novel cell populations with poorly understood biology. Following discovery, characterization of these populations in terms of the critical markers involved is an important step, as this can help to both better understand the biology of these populations and aid in designing simpler marker panels to identify them on simpler instruments and with fewer reagents (i.e., in resource poor or highly regulated clinical settings). However, current tools to design panels based on the biological characteristics of the target cell populations work exclusively based on technical parameters (e.g., instrument configurations, spectral overlap, and reagent availability). To address this shortcoming, we developed RchyOptimyx (cellular hieraRCHY OPTIMization), a computational tool that constructs cellular hierarchies by combining automated gating with dynamic programming and graph theory to provide the best gating strategies to identify a target population to a desired level of purity or correlation with a clinical outcome, using the simplest possible marker panels. RchyOptimyx can assess and graphically present the trade-offs between marker choice and population specificity in high-dimensional flow or mass cytometry datasets. We present three proof-of-concept use cases for RchyOptimyx that involve 1) designing a panel of surface markers for identification of rare populations that are primarily characterized using their intracellular signature; 2) simplifying the gating strategy for identification of a target cell population; 3) identification of a non-redundant marker set to identify a target cell population. (C) 2012 International Society for Advancement of Cytometry