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）”的计划补助金，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，对无墙（CWW）的关键需求（CWW），该中心（CWW）专注于抗杀菌生成（AEG）。需要癫痫发生的生物标志物来限制研究人群，通过识别那些在潜在的癫痫发作脑损伤后患有癫痫病风险最高的患者，并进行癫痫发作过程。在II期临床试验中，需要作为替代标记的癫痫发作的生物标志物，以记录预防或治愈。从现有的动物和患者数据中，我们假设三种最有前途的生物标志物将源自脑电图（EEG）的纵向研究（EEG），神经影像学和分子变化，在癫痫发生过程中发生，以及癫痫发育后存在。此外，我们预计不会出现任何可靠的生物标志物，但是预测能力将需要生物标志物的组合。为了开始寻找生物标志物，我们将利用现有的生物信息学平台来分析可用的多模型数据，从患者和动物的癫痫发育和癫痫发作期间从患者和动物那里收集，以识别最可能的个体生物标记物，并确定癫痫生成和癫痫生成和动物模型的生物标志物的最可能的生物标志物，并确定原模型的最佳模型。预期的问题将在半年度专注的研讨会上解决。在此授予期结束时，我们打算提交三个可交付成果：1）身份证明和验证 最有可能使用来自正在进行的动物和人类研究的数据的生物标志物； 2）至少六个研讨会得出的有关策略和解决问题的综合立场论文，以及3）国际，多模式，交互式，开放式，开放访问，生物信息学网格，可用于对癫痫生成和癫痫生成的生物学生物标志物进行大量前瞻性临床研究。我们还打算利用这项研究的结果来为癫痫生成的基本机制和对AEG的新目标（对于CWW所必需的新目标）提供信息，并预测这种生物信息学方法是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