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）：我们提议提供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，方法是识别潜在的致癫痫脑损伤后癫痫风险最高的患者，并分阶段进行致癫痫过程。致癫痫性的生物标志物需要作为 II 期临床试验的替代标志物，以记录预防或治疗。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源自对癫痫发生过程中发生的脑电图（EEG）、神经影像学和分子变化的纵向研究以及癫痫发展后存在的分子变化。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。为了快速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在癫痫发展过程中从患者和动物纵向收集的可用多模态数据，以及癫痫，以确定最有可能的个体生物标志物，和/或癫痫发生和致癫痫性的生物标志物组合，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研讨会上得到解决。在此授权期结束时，我们打算提交三项可交付成果：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综合立场文件，以及 3) 国际性、多模态、交互式、开放获取、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为癫痫发生的基本机制的调查和寻找对于 CwW 至关重要的 AEG 新靶点提供信息，并预计这种生物信息学方法将成为生物医学研究的未来。

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