A simple way to detect disease-associated cellular molecular alterations from mixed-cell blood samples. (14th February 2017)

• Record Type: Journal Article
• Authors: Hong, Guini; Li, Hongdong; Li, Mengyao; Zheng, Weicheng; Li, Jing; Chi, Meirong; Cheng, Jun; Guo, Zheng
• Is Part Of: Briefings in bioinformatics. Volume 19:Number 4(2018:Jul.)
• Page Start: 613
• Page End: 621
• Publication Date: 2017-02-14
• Subjects: leukocyte subtypes -- relative expression orderings -- cell-mixed; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbx009
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Blood is a promising surrogate for solid tissue to investigate disease-associated molecular biomarkers. However, proportion changes of the constituent cells in the often-used peripheral whole blood (PWB) or peripheral blood mononuclear cell (PBMC) samples may influence the detection of cell-specific alterations under disease states. We propose a simple method, Ref-REO, to detect molecular alterations in leukocytes using the mixed-cell blood samples. The method is based on the predetermined within-sample relative expression orderings (REOs) of genes in purified leukocytes of healthy people. Both the simulated and real mixed-cell blood gene expression profiles were used to evaluate the method. Approximately 99% of the differentially expressed genes (DEGs) detected by Ref-REO in the simulated mixed-cell data are owing to the transcriptional alterations in leukocytes rather than the proportion changes of leukocytes. For the real mixed-cell data, the DEGs detected by Ref-REO in the PBMCs expression data for systemic lupus erythematosus (SLE) patients overlap significantly with the DEGs detected in the expression data of SLE CD4 + T cells and B cells and they are mainly enriched with mRNA editing and interferon-associated genes. The detected DEGs in the PWB data for lung carcinoma patients are significantly enriched with coagulation-associated functional categories that are closely associated with cancer progression. In conclusion, the proposed method is capable of detecting the disease-associated leukocyte-specific molecular alterations, using mixed-cell blood samples, which provides simple, transferable and easy-to-use candidates for disease biomarkers.