non-gaussian distributions affect identification of expression patterns, functional annotation, and prospective classification in human cancer genomes非高斯分布影响识别的表达模式,在人类癌症基因组功能注释和潜在分类.pdfVIP

Non-Gaussian Distributions Affect Identification of Expression Patterns, Functional Annotation, and Prospective Classification in Human Cancer Genomes 1 2 Nicholas F. Marko *, Robert J. Weil 1 Cancer Research United Kingdom Cambridge Research Institute and Department of Applied Mathematics and Theoretical Physics, Cambridge University, Cambridge, United Kingdom, 2 Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, United States of America Abstract Introduction: Gene expression data is often assumed to be normally-distributed, but this assumption has not been tested rigorously. We investigate the distribution of expression data in human cancer genomes and study the implications of deviations from the normal distribution for translational molecular oncology research. Methods: We conducted a central moments analysis of five cancer genomes and performed empiric distribution fitting to examine the true distribution of expression data both on the complete-experiment and on the individual-gene levels. We used a variety of parametric and nonparametric methods to test the effects of deviations from normality on gene calling, functional annotation, and prospective molecular classification using a sixth cancer genome. Results: Central moments analyses reveal statistically-significant deviations from normality in all of the analyzed cancer genomes. We observe as much as 37% variability in gene calling, 39% variability in functional annotation, and 30% variability in prospective, molecular tumor subclassification associated with this effect. Conclusions: Cancer gene expression profiles are not normally-distributed, either on the complete-experiment or on the individual-gene level. Instead, they exhibit complex, heavy-tailed distributions characterized