Statistical methods of translating microarray data into clinically relevant diagnostic information in colorectal cancer
Authors:
Open Access
- 16 September 2004
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in Bioinformatics
- Vol. 21 (4) , 517-528
Abstract
Motivation: It is a common practice in cancer microarray experiments that a normal tissue is collected from the same individual from whom the tumor tissue was taken. The indirect design is usually adopted for the experiment that uses a common reference RNA hybridized both to normal and tumor tissues. However, it is often the case that the test material is not large enough for the experimenter to extract enough RNA to conduct the microarray experiment. Hence, collecting ncases does not necessarily end up with a matched pair sample of size n. Instead we usually have a matched pair sample of size n1, and two independent samples of sizes n2 and n3, respectively, for ‘reference versus normal tissue only’ and ‘reference versus tumor tissue only’ hybridizations (n = n1 + n2 + n3). Standard statistical methods need to be modified and new statistical procedures are developed for analyzing this mixed dataset. Results: We propose a new test statistic, t3, as a means of combining all the information in the mixed dataset for detecting differentially expressed (DE) genes between normal and tumor tissues. We employed the extended receiver operating characteristic approach to the mixed dataset. We devised a measure of disagreement between a RT–PCR experiment and a microarray experiment. Hotelling's T2 statistic is employed to detect a set of DE genes and its prediction rate is compared with the prediction rate of a univariate procedure. We observe that Hotelling's T2 statistic detects DE genes more efficiently than a univariate procedure and that further research is warranted on the formal test procedure using Hotelling's T2 statistic. Contact:bskim@yonsei.ac.krKeywords
This publication has 21 references indexed in Scilit:
- Statistical Issues in the Search for Biomarkers of Colorectal Cancer Using Microarray Experiments2005
- Multivariate exploratory tools for microarray data analysisBiostatistics, 2003
- Association of ets‐related transcriptional factor E1AF expression with tumour progression and overexpression of MMP‐1 and matrilysin in human colorectal cancerThe Journal of Pathology, 2003
- A Gene-Expression Signature as a Predictor of Survival in Breast CancerNew England Journal of Medicine, 2002
- A Direct Approach to False Discovery RatesJournal of the Royal Statistical Society Series B: Statistical Methodology, 2002
- The Use of Molecular Profiling to Predict Survival after Chemotherapy for Diffuse Large-B-Cell LymphomaNew England Journal of Medicine, 2002
- Comparison of Discrimination Methods for the Classification of Tumors Using Gene Expression DataJournal of the American Statistical Association, 2002
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences, 2001
- Gene-Expression Profiles in Hereditary Breast CancerNew England Journal of Medicine, 2001
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000