The Epilepsy Bioinformatics Study (EpiBioS)

描述(由申请人提供)：我们提出了一项名为癫痫生物信息学研究(EpiBioS)的规划拨款，以开发一种生物信息学方法来识别可靠的癫痫生物标志物，这是一个专注于抗癫痫发生(AEG)的无墙中心(CWW)的迫切需要。需要癫痫发生的生物标志物来限制研究人群，通过识别那些潜在的致痫脑损伤后癫痫风险最高的患者，并对癫痫形成过程进行分期。在II期临床试验中，致痫的生物标记物需要作为替代标记物，以证明预防或治愈。根据现有的动物和患者数据，我们假设最有希望的三类生物标志物将来自对脑电(EEG)、神经成像和癫痫发生过程中发生的分子变化的纵向研究，并在癫痫发生后存在。此外，我们预计不会出现单一可靠的生物标记物，但预测能力将需要生物标记物的组合。为了启动对生物标记物的搜索，我们将利用现有的生物信息学平台来分析在癫痫发展过程中从患者和动物那里纵向收集的可用的多模式数据，以识别最可能的单个生物标记物，以及/或癫痫发生和致痫的生物标记物的组合，并确定用于未来研究的最佳动物模型。预期的问题将在半年一次的重点讲习班上讨论。在此授权期结束时，我们打算提交三项交付成果：1)确定和验证 最有可能使用正在进行的动物和人类研究得出的数据的生物标记物；2)从至少六个研讨会得出的关于战略和解决问题的综合立场文件，以及3)一个国际的、多模式的、互动的、开放获取的生物信息学网格，可用于对癫痫发生和致痫的生物标记物进行的大型前瞻性临床研究。我们还打算利用这项研究的结果，为癫痫发生的基本机制提供信息，并为AEG寻找新的靶点，这对CWW至关重要，并预期这种生物信息学方法将成为生物医学研究的未来。

DESCRIPTION (provided by applicant): We propose a planning grant titled the Epilepsy Bioinformatics Study (EpiBioS) to develop a bioinformatics approach to identify reliable epilepsy biomarkers, a critical need for a Center without Walls (CwW) focused on antiepileptogenesis (AEG). Biomarkers of epileptogenesis are needed to limit the study population by identifying those patients at highest risk for epilepsy after a potential epileptogenic brain insult, and to stage the epileptogenic process. Biomarkers of epileptogenicity are needed as surrogate markers in Phase II clinical trials, to document prevention or cure. From existing animal and patient data, we hypothesize that the three most promising classes of biomarkers will be derived from longitudinal studies of electroencephalographic (EEG), neuroimaging, and molecular changes occurring during the process of epileptogenesis, and existing after the development of epilepsy. Furthermore, we anticipate that no single reliable biomarker will emerge, but that predictive power will require a combination of biomarkers. To jumpstart the search for biomarkers we will utilize existing bioinformatics platforms to analyze available multimodality data longitudinally collected from patients and animals during development of epilepsy, and with epilepsy, to identify the most likely individual biomarkers, and/or combinations of biomarkers of epileptogenesis and epileptogenicity, and to determine the best animal models for future studies. Anticipated problems will be addressed at semiannual focused workshops. At the end of this granting period we intend to submit three deliverables: 1) identification and validation of the most likely biomarkers using data derived from ongoing animal and human studies; 2) comprehensive position papers on strategy and problem solving derived from at least six workshops, and 3) an international, multimodality, interactive, open access, bioinformatics grid available for a large prospective clinical study of biomarkers of epileptogenesis and epileptogenicity. We also intend to use the results of this study to inform investigations into the basic mechanisms of epileptogenesis and the search for novel targets for AEG, essential to the CwW, and anticipate this bioinformatics approach to be the future of biomedical research.