STATISTICAL EVALUATION OF CELL KINETIC DATA FROM DNA FLOW-CYTOMETRY (FCM) BY THE EM ALGORITHM

STATISTICAL EVALUATION OF CELL KINETIC DATA FROM DNA FLOW-CYTOMETRY (FCM) BY THE EM ALGORITHM
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DOI:
10.1002/cyto.990100605
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发表时间:
1989-11-01
期刊:
CYTOMETRY
影响因子:
--
通讯作者:
LINDGREN, G
LINDGREN, G
中科院分区:
其他
文献类型:
--
作者:
BALDETORP, B;DALBERG, M;LINDGREN, G

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流式细胞仪DNA测量产生大量细胞的每个DNA的量。DNA直方图通常由一个或多个G0/G1期、S期、G2/ m期细胞群、内部标准、碎片、背景噪声和一个或多个团块细胞群的混合物组成。我们将典型的DNA直方图建模为混合分布,G0/G1期和G2/M期具有高斯密度,s期密度假设在G0/G1和G2/M峰之间是均匀的,观察时具有高斯误差,鸡和鳟鱼红细胞的标准具有高斯密度。碎片被建模为截断的指数分布,我们还在整个观测区间内包含了均匀的背景噪声分布。我们探索了一种应用EM算法对复杂DNA直方图进行最大似然分析的新方法。该算法用于四个不同复杂度的DNA直方图。实验结果表明,该算法能很好地收敛到所有参数的合理值。在估计模型的模拟中,我们研究了偏差方差和估计的相关性。
Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, and S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias variance, and correlations of the estimates.