title: Investigation of variation in gene expression profiling of human blood by extended principle component analysis.
abstract: BACKGROUND
  Human peripheral blood is a promising material for biomedical research. However, various kinds of biological and technological factors result in a large degree of variation in blood gene expression profiles.
  
  
  RESULTS
  Human peripheral blood samples were drawn from healthy volunteers and analysed using the Human Genome U133Plus2 Microarray. We applied a novel approach using the Principle Component Analysis and Eigen-R(2) methods to dissect the overall variation of blood gene expression profiles with respect to the interested biological and technological factors. The results indicated that the predominating sources of the variation could be traced to the individual heterogeneity of the relative proportions of different blood cell types (leukocyte subsets and erythrocytes). The physiological factors like age, gender and BMI were demonstrated to be associated with 5.3% to 9.2% of the total variation in the blood gene expression profiles. We investigated the gene expression profiles of samples from the same donors but with different levels of RNA quality. Although the proportion of variation associated to the RNA Integrity Number was mild (2.1%), the significant impact of RNA quality on the expression of individual genes was observed.
  
  
  CONCLUSIONS
  By characterizing the major sources of variation in blood gene expression profiles, such variability can be minimized by modifications to study designs. Increasing sample size, balancing confounding factors between study groups, using rigorous selection criteria for sample quality, and well controlled experimental processes will significantly improve the accuracy and reproducibility of blood transcriptome study.
authors: Fudan University Shanghai Cancer Center - Institut Mérieux Laboratory, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors: Qinghua
authors: Q
authors: Xu
authors: Shujuan
authors: S
authors: Ni
authors: Fei
authors: F
authors: Wu
authors: Fang
authors: F
authors: Liu
authors: Xun
authors: X
authors: Ye
authors: Bruno
authors: B
authors: Mougin
authors: Xia
authors: X
authors: Meng
authors: Xiang
authors: X
authors: Du
mesh_terms: D001773:Blood Cells / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D025341:Principal Component Analysis; D012107:Research Design / Q000592:standards; D059467:Transcriptome
chemical_list: D001798:Blood Proteins