Highthroughput analysis of behavior for CNS applications

描述（由申请人提供）：本申请是为了响应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。该项目的目标是通过利用我们在小鼠行为药理学方面的专业知识开发Smart cube，一种行为，神经和生理分析的自动化高通量系统，以缓解精神药物和靶点发现和新突变体表征的瓶颈。智能立方体将包括创新的机器人硬件和机器学习算法，以捕捉和整合行为和生理状态。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、抗焦虑药和其他经证实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，以提供快速准确的新药治疗潜力指数。智能立方体将促进当前的行为研究，药物发现，目标验证和快速表征突变小鼠的目标基因操作和诱变工作。该快速通道提案的第一阶段将开发SmartCube，以自动分类小鼠行为，表征近交系小鼠在包括抗焦虑和抗精神病药物在内的不同药理干预影响下的行为反应，并在不受限制的小鼠中开发集成的非侵入性ECG，该ECG将与行为的自动分析同时运行。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，以自动分类行为，区分药物特征，并将开发Smart Base，一个大型药物特征集合及其相关的生物信息学工具，以执行复杂的数据挖掘。 商业价值：非常需要改进候选药物和突变体的数据收集和分析。 通过提供行为测试吞吐量的大幅增加（约100倍），以及伴随生物信息学工具的规范数据，Smart cube系统将促进当前的行为研究（通过更快，更可靠地执行已知的标准模型），CNS新药发现（通过筛选整个药物库）和CNS靶点验证（通过快速表征新的突变小鼠）。 Smart Base以其累积的规范性数据在近交系小鼠中将有很大的影响和价值。

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.