A Simulation Study for Evaluation in Estimation of Fold Change from Gene Expression Data in Microarray Experiments
Date Issued
2006
Date
2006
Author(s)
Cheng, Hui-Ping
DOI
en-US
Abstract
High density oligonucleotide arrays allow scientists to monitor expression levels of thousands of genes simultaneously. Currently Affymetrix high-density oligonucleotide array is one of the most frequently employed array products. Scientists use the expression data of genes from microarray experiments to estimate relative change in expression levels between two conditions. Fold change, defined as the ratio of mean expression level of a gene under one condition to that of the same gene under another condition. Current approach first is to take logarithmic transformation (based on 2) of the original expression data. Next the difference of the arithmetic means on the log-scale between the two conditions is computed. The current approach implicitly assumes that the expression levels follow the log-normal distribution and is the maximum likelihood estimate (MLE) of the fold change. However, MLE is a biased estimator of the fold change and minimum variance estimator (MVUE) of the fold change exists under the log-normal distribution. To investigate the bias and variability of the two estimators, a simulation study was conducted under of various combinations of the number of assays, variability, and number of probe cells. In simulation study, the data were generated by the four methods proposed for the expression levels by Affymetrix high-density oligonucleotide array. They are robust multi-array average (RMA) and PM/MM difference, PM-only and SUM model of based expression index (MBEI). Simulation results show that the bias of MLE is smaller than that of MVUE and the mean square error of MLE is greater than the mean square error of MVUE. The simulation findings are not in agreement of the theoretical results. This suggests that the data generated by RMA, and MBEI do not follow a log-normal distribution.
Subjects
相對表現量
最大概似估計法
最小變異不偏估計法
Robust multi-array average (RMA)
Model based expression index (MBEI)
Fold change
Maximum likelihood estimator (MLE)
Minimum variance unbiased estimator (MVUE)
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-95-R93621202-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):11918130602c1b732383a834c1b61d10