Department of Bioinformatics, Fujian Medical University, Fuzhou, China.
Brief Bioinform. 2018 Jul 20;19(4):613-621. doi: 10.1093/bib/bbx009.
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.
血液是一种有前途的替代实体组织的方法，可用于研究与疾病相关的分子生物标志物。然而，通常使用的外周全血（PWB）或外周血单个核细胞（PBMC）样本中组成细胞的比例变化可能会影响在疾病状态下对细胞特异性改变的检测。我们提出了一种简单的方法 Ref-REO，用于使用混合细胞血液样本检测白细胞中的分子变化。该方法基于健康人纯化白细胞中基因的预定样本内相对表达顺序（REO）。模拟和真实混合细胞血液基因表达谱均用于评估该方法。在模拟混合细胞数据中，Ref-REO 检测到的差异表达基因（DEG）中约有 99%是由于白细胞的转录改变，而不是白细胞比例的变化。对于真实的混合细胞数据，Ref-REO 在系统性红斑狼疮（SLE）患者的 PBMCs 表达数据中检测到的 DEG 与在 SLE CD4+T 细胞和 B 细胞的表达数据中检测到的 DEG 显著重叠，它们主要富集与 mRNA 编辑和干扰素相关的基因。在肺癌患者的 PWB 数据中检测到的 DEG 显著富集与癌症进展密切相关的凝血相关功能类别。总之，该方法能够使用混合细胞血液样本检测与疾病相关的白细胞特异性分子变化，为疾病生物标志物提供了简单、可转移和易于使用的候选物。
