Highthroughput analysis of behavior for CNS applications

描述(申请人提供)：本申请是针对SBIR征集中的NIMH研究主题、神经科学和基础行为科学而提交的。该项目的目标是利用我们在小鼠行为药理学方面的专业知识开发Smart Cube，这是一种行为、神经和生理分析的自动化高通量系统，以缓解精神药物以及新突变体的目标发现和表征方面的瓶颈。智能立方体将包括创新的类似机器人的硬件，以及捕捉和集成行为和生理状态的机器学习算法。Smart Cube将以一个大型药理学数据库为中心，该数据库包括抗精神病药物、抗焦虑药物和其他已被证明对人类有效的药物的药物概况，并将配备最先进的生物信息学，以提供对新药治疗潜力的快速和准确的索引。智能立方体将促进当前的行为研究、药物发现、目标验证以及从目标基因操作和突变努力中对突变小鼠的快速表征。这项快速通道提案的第一阶段将开发SmartCube，以自动对小鼠的行为进行分类，表征近交系小鼠在不同药物干预(包括抗焦虑和抗精神病药物)影响下的行为反应，并开发一种集成的非侵入性小鼠心电，它将与行为自动分析同时运行。该提案的第二阶段包括在随附的申请中，将进一步开发SmartCube功能，以自动对行为进行分类，区分药物配置文件，并将开发Smart Base，这是一个大型药物配置文件集合，及其相关的生物信息工具，用于执行复杂的数据挖掘。 商业价值：非常需要改进对候选药物和突变体的数据收集和分析。通过提供大幅增加的行为测试吞吐量(约100倍)和伴随的生物信息学工具的标准化数据，Smart Cube系统将促进当前的行为研究(通过更快和更可靠地执行已知标准模型)、中枢神经系统新药发现(通过筛选整个药库)和中枢神经系统靶标验证(通过快速确定新型突变小鼠的特征)。Smart Base以其累积的规范数据在近交系小鼠中将产生巨大的影响和价值。

DESCRIPTION (provided by applicant): This application is submitted in response to the NIMH research topic, neuroscience and basic behavioral science in the SBIR solicitation. The goal of this project is to alleviate the bottleneck in psychiatric drug and target discovery and characterization of novel mutants by using our expertise in behavioral pharmacology in mice to develop Smart cube, an automated high-throughput system of behavioral, neurological and physiological analysis. Smart cube will comprise innovative robotic-like hardware, and machine-learning algorithms to capture and integrate behavioral and physiological states. Smart Cube will be centered around a large pharmacological database comprised of drug profiles of antipsychotics, anxiolytics and other drugs of proven efficacy in humans and will be equipped with state of the art bioinformatics to provide rapid and accurate indices of the therapeutic potential of novel drugs. Smart cube will facilitate current behavioral research, drug discovery, target validation and fast characterization of mutant mice from target gene manipulation and mutagenesis efforts. Phase I of this Fast Track proposal will develop SmartCube to automatically classify mouse behavior, to characterize the behavioral response of inbred strains of mice under the influence of different pharmacological interventions covering anxiolytic and antipsychotic drugs and to develop an integrated non-invasive ECG in unrestrained mice, which will run simultaneously with the automated analysis of behavior. Phase II of this proposal, included in the accompanying application, will further develop SmartCube capabilities to automatically classify behaviors, discriminate between drug profiles and will develop Smart Base, a large collection of drug profiles, and its associated bioinformatic tools to perform sophisticated data mining. Commercial Value: There is a great need to improve data collection and analysis of drug candidates and mutants. By providing a substantial increase in the throughput of behavioral testing (about 100 fold), and normative data with accompanying bioinformatic tools, the Smart cube system will facilitate current behavioral research (by performing known standard models faster and more reliably), CNS novel drug discovery (by screening whole drug libraries) and CNS target validation (by quickly characterizing novel mutant mice). Smart Base, with its cumulative normative data in inbred mice will have great impact and value.