Immune cell gene expression and predictive models in CFS

描述（由申请人提供）：慢性疲劳综合征目前被诊断为一系列症状，这些症状限制了其识别，直到发病后至少6个月。此外，缺乏客观的分子或生化测试，可以由不熟悉疾病的医务人员订购，往往导致进一步延误和误诊为其他疲劳性疾病。治疗选择是有限的。新疗法的发展受到以下几个障碍的阻碍：(1)缺乏简单客观的监测工具来确定治疗是否有效；(2)难以区分可能的患者亚群；(3)缺乏有关疾病病理生理学的信息，这些信息可能提示开发新型药物。这些问题将通过使用最先进的深度测序方法和生物信息学分析来识别CFS患者和健康对照组之间的基因表达差异来解决。过去的研究表明感染因子、自身免疫或免疫系统紊乱会影响循环白细胞的活性。流式细胞术纯化的全血和B、T、NK细胞的信使rna和微小rna将通过Illumina条形码cDNA文库测序进行表征。候选mrna编码基因失调子集的表达将在蛋白水平上进行检测。标记将在独立于发现地点的群体中得到确认。将开发和验证多变量生物标志物模型，以预测诊断和疾病严重程度。免疫细胞基因表达的综合分析将有助于进一步了解CFS的发病机制。

DESCRIPTION (provided by applicant): Chronic fatigue syndrome is presently diagnosed by a constellation of symptoms, which limit its identification until a minimum of 6 months after disease onset. Furthermore, the lack of an objective molecular or biochemical test that can be ordered by medical personnel unfamiliar with the illness often results in even further delay and misdiagnosis with other fatiguing illnesses. Treatment options are limited. Development of new therapies is hindered by several obstacles: (1) the absence of simple objective monitoring tools to determine whether a therapy is efficacious (2) difficulty in distinguishing possible sub-groups of patients and (3) lack of information about the pathophysiology of the disease that could suggest development of novel medications. These problems will be attacked through identification of gene expression differences between CFS patients and healthy controls using state-of-the-art deep sequencing methods and bioinformatic analysis. Past studies implicate infectious agents, autoimmunity, or immune system disturbances that affect the activity of circulating leukocytes. Messenger RNAs and microRNAs from whole blood and B, T, and NK cells purified by flow cytometry will be characterized through Illumina sequencing of barcoded cDNA libraries. The expression of a subset of candidate dysregulated mRNA-encoding genes will be assayed at the protein level. Markers will be confirmed in cohorts independent of those where they have been discovered. Multivariate biomarker models will be developed and validated in order to predict diagnosis as well as disease severity. Integrative analyses of immune cell gene expression will be carried out to help further our understanding of CFS pathogenesis.