The Epilepsy Bioinformatics Study (EpiBioS)

癫痫生物信息学研究 (EpiBioS)

• 批准号: 8725243
• 负责人: JEROME NONE ENGEL
• 金额: $ 60.58万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725243
• 关键词: Address; Animal Model; Animals; Antiepileptogenic; Behavioral; Bioinformatics; Biological Markers; Biomedical Research; Blood; Brain; Brain Diseases; California; Cerebrospinal Fluid; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Craniocerebral Trauma; Data; Data Analyses; Development; Diagnosis; Documentation; Educational workshop; Electrophysiology (science); Epilepsy; Epileptogenesis; Fever; Future; Genetic; Grant; Human; Human Resources; Image; Individual; Injury; International; Internet; Intervention; Investigation; Laboratories; Longitudinal Studies; Los Angeles; Measures; Methods; Molecular; Paper; Patients; Pennsylvania; Phase II Clinical Trials; Population Study; Positioning Attribute; Post-Traumatic Epilepsy; Prevention; Preventive Intervention; Problem Solving; Process; Risk; Scalp structure; Seizures; Severities; Staging; Status Epilepticus; Structure; Surrogate Markers; System; Temporal Lobe Epilepsy; Time; Traumatic Brain Injury; Universities; Validation; computing resources; high risk; multimodality; neocortical; neuroimaging; novel; patient population; prevent; programs; prospective; public health relevance; tool

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.

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）的计划拨款，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（AEG）的无墙中心（CwW）的关键需求。需要癫痫发生的生物标志物来限制研究人群，通过识别潜在癫痫脑损伤后癫痫风险最高的患者，并对癫痫过程进行分期。在II期临床试验中，需要癫痫发生的生物标志物作为替代标志物，以记录预防或治愈。从现有的动物和患者的数据，我们假设，三个最有前途的生物标志物类将来自纵向研究脑电图（EEG），神经影像学和分子变化过程中发生的癫痫，并存在发展后的癫痫。此外，我们预计不会出现单一可靠的生物标志物，但预测能力将需要生物标志物的组合。为了启动生物标志物的搜索，我们将利用现有的生物信息学平台来分析从癫痫发展过程中的患者和动物纵向收集的可用多模态数据，并与癫痫一起，以确定最可能的个体生物标志物和/或癫痫发生和癫痫发生的生物标志物组合，并确定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。在这一授予期结束时，我们打算提交三个可交付成果：1）识别和验证 使用来自正在进行的动物和人类研究的数据来确定最有可能的生物标志物; 2）来自至少六个研讨会的关于策略和问题解决的全面立场文件，以及3）国际、多模式、交互式、开放获取的生物信息学网格，可用于癫痫发生和致癫痫性生物标志物的大型前瞻性临床研究。我们还打算利用这项研究的结果，通知调查癫痫发生的基本机制和寻找新的目标AEG，必不可少的CwW，并预计这种生物信息学方法是未来的生物医学研究。

项目成果

Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy.

• DOI: 10.1126/scitranslmed.aaa7095
• 发表时间: 2015-10-14
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Davis KA;Nanga RP;Das S;Chen SH;Hadar PN;Pollard JR;Lucas TH;Shinohara RT;Litt B;Hariharan H;Elliott MA;Detre JA;Reddy R
• 通讯作者: Reddy R