Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, California 92697-4260, USA.
Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 5;153B(4):919-36. doi: 10.1002/ajmg.b.31062.
The consistency of peripheral gene expression data and the overlap with brain expression has not been evaluated in biomarker discovery, nor has it been reported in multiple tissues from the same subjects on a genome wide transcript level. The effects of processing whole blood, transformation, and passaged cell lines on gene expression profiling was studied in healthy subjects using Affymetrix arrays. Ficoll extracted peripheral blood mononuclear cells (PBMCs), Epstein-Barr virus (EBV) transformed lymphocytes, passaged lymphoblastic cell lines (LCLs), and whole blood from Tempus tubes were compared. There were 6,813 transcripts differentially expressed between different methods of blood preparation. Principal component analysis resolved two partitions involving pre- and post-transformation EBV effects. Combining results from Affymetrix arrays, postmortem subjects' brain and PBMC profiles showed co-expression levels of summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts. In a control experiment, rat hemi-brain and blood showed similar expression levels for 19% of RefSeq transcripts. After filtering transcripts that were not significantly different in abundance between human cerebellum and PBMCs from the Affymetrix exon array the correlation in mean transcript abundance was high as expected (r = 0.98). Differences in the alternative splicing index in brain and blood were found for about 90% of all transcripts examined. This study demonstrates over 4,100 brain transcripts co-expressed in blood samples can be further examined by in vitro and in vivo experimental studies of blood and cell lines from patients with psychiatric disorders.
在外周基因表达数据的一致性和与大脑表达的重叠方面，在生物标志物发现中尚未得到评估，也未在同一受试者的多个组织中在全基因组转录水平上进行过报道。在健康受试者中，使用 Affymetrix 芯片研究了全血处理、转化和传代细胞系对基因表达谱的影响。比较了 Ficoll 提取的外周血单核细胞（PBMCs）、EB 病毒（EBV）转化的淋巴细胞、传代的淋巴母细胞系（LCL）和 Tempus 管中的全血。不同的血液制备方法之间有 6813 个转录本差异表达。主成分分析解决了涉及 EBV 转化前后效应的两个分区问题。将 Affymetrix 芯片的结果结合起来，尸检受试者的大脑和 PBMC 图谱显示，在 17859 个 RefSeq 转录本中有 4103 个转录本的汇总转录物的共表达水平。在对照实验中，大鼠半脑和血液显示 19%的 RefSeq 转录本具有相似的表达水平。从 Affymetrix 外显子芯片中过滤掉在人脑小脑和 PBMC 之间丰度没有显著差异的转录本后，预期平均转录本丰度的相关性很高（r=0.98）。在大脑和血液中发现了约 90%的所有转录本的可变剪接指数存在差异。这项研究表明，在血液样本中可以进一步研究 4100 多个与大脑共表达的转录本，通过对精神疾病患者的血液和细胞系进行体外和体内实验研究。
