Ghavami Siavash, Wolkenhauer Olaf, Lahouti Farshad, Ullah Mukhtar, Linnebacher Michael
Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany.
Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
IET Syst Biol. 2014 Oct;8(5):230-41. doi: 10.1049/iet-syb.2013.0031.
Knowing the expected temporal evolution of the proportion of different cell types in sample tissues gives an indication about the progression of the disease and its possible response to drugs. Such systems have been modelled using Markov processes. We here consider an experimentally realistic scenario in which transition probabilities are estimated from noisy cell population size measurements. Using aggregated data of FACS measurements, we develop MMSE and ML estimators and formulate two problems to find the minimum number of required samples and measurements to guarantee the accuracy of predicted population sizes. Our numerical results show that the convergence mechanism of transition probabilities and steady states differ widely from the real values if one uses the standard deterministic approach for noisy measurements. This provides support for our argument that for the analysis of FACS data one should consider the observed state as a random variable. The second problem we address is about the consequences of estimating the probability of a cell being in a particular state from measurements of small population of cells. We show how the uncertainty arising from small sample sizes can be captured by a distribution for the state probability.
了解样本组织中不同细胞类型比例的预期时间演变,可为疾病进展及其对药物的可能反应提供线索。此类系统已使用马尔可夫过程进行建模。我们在此考虑一种实验上现实的情况,即从有噪声的细胞群体大小测量中估计转移概率。利用流式细胞术测量的汇总数据,我们开发了最小均方误差(MMSE)和最大似然(ML)估计器,并提出两个问题,以找到保证预测群体大小准确性所需的最少样本数和测量次数。我们的数值结果表明,如果使用标准确定性方法处理有噪声的测量数据,转移概率和稳态的收敛机制与实际值有很大差异。这支持了我们的观点,即对于流式细胞术数据分析,应将观察到的状态视为随机变量。我们解决的第二个问题是关于从小细胞群体测量中估计细胞处于特定状态的概率的后果。我们展示了如何通过状态概率分布来捕捉小样本量产生的不确定性。