Hardy Jimmaline J, Mooney Scott R, Pearson Andrea N, McGuire Dawn, Correa Daniel J, Simon Roger P, Meller Robert
Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States of America.
Neuroscience & Rehabilitation Center, Dwight D. Eisenhower Army Medical Center, Fort Gordon, Georgia, United States of America.
PLoS One. 2017 Sep 1;12(9):e0183113. doi: 10.1371/journal.pone.0183113. eCollection 2017.
Mild traumatic brain injury (mTBI) is a complex, neurophysiological condition that can have detrimental outcomes. Yet, to date, no objective method of diagnosis exists. Physical damage to the blood-brain-barrier and normal waste clearance via the lymphatic system may enable the detection of biomarkers of mTBI in peripheral circulation. Here we evaluate the accuracy of whole transcriptome analysis of blood to predict the clinical diagnosis of post-concussion syndrome (PCS) in a military cohort. Sixty patients with clinically diagnosed chronic concussion and controls (no history of concussion) were recruited (retrospective study design). Male patients (46) were split into a training set comprised of 20 long-term concussed (> 6 months and symptomatic) and 12 controls (no documented history of concussion). Models were validated in a testing set (control = 9, concussed = 5). RNA_Seq libraries were prepared from whole blood samples for sequencing using a SOLiD5500XL sequencer and aligned to hg19 reference genome. Patterns of differential exon expression were used for diagnostic modeling using support vector machine classification, and then validated in a second patient cohort. The accuracy of RNA profiles to predict the clinical diagnosis of post-concussion syndrome patients from controls was 86% (sensitivity 80%; specificity 89%). In addition, RNA profiles reveal duration of concussion. This pilot study shows the potential utility of whole transcriptome analysis to establish the clinical diagnosis of chronic concussion syndrome.
轻度创伤性脑损伤（mTBI）是一种复杂的神经生理状况，可能会产生有害后果。然而，迄今为止，尚无客观的诊断方法。血脑屏障的物理损伤以及通过淋巴系统的正常废物清除可能有助于在外周循环中检测mTBI的生物标志物。在此，我们评估血液全转录组分析预测军事队列中脑震荡后综合征（PCS）临床诊断的准确性。招募了60例临床诊断为慢性脑震荡的患者和对照组（无脑震荡病史）（回顾性研究设计）。男性患者（46例）被分为一个训练集，其中包括20例长期脑震荡患者（>6个月且有症状）和12例对照组（无脑震荡记录病史）。模型在一个测试集中进行验证（对照组=9例，脑震荡组=5例）。使用SOLiD5500XL测序仪从全血样本制备RNA_Seq文库进行测序，并与hg19参考基因组比对。使用支持向量机分类法将差异外显子表达模式用于诊断建模，然后在第二个患者队列中进行验证。RNA谱预测脑震荡后综合征患者与对照组临床诊断的准确性为86%（敏感性80%；特异性89%）。此外，RNA谱揭示了脑震荡的持续时间。这项初步研究表明全转录组分析在确立慢性脑震荡综合征临床诊断方面的潜在效用。
