Web Software for Drug Targeting Signaling Networks in Primary Cell Subsets

原代细胞亚群药物靶向信号网络网络软件

• 批准号: 8058881
• 负责人: Nikesh Kotecha
• 金额: $ 15.02万
• 依托单位: CYTOBANK, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-09 至 2013-02-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8058881
• 关键词: Address; Adverse effects; Autoimmune Diseases; Autoimmunity; Automobile Driving; Basic Science; Biochemical; Biochemistry; Bioinformatics; Biological Assay; Biology; Biotechnology; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Communication; Communities; Complex; Computer software; Cytometry; Data; Data Analyses; Data Files; Development; Diagnostic; Discipline; Disease; Dose; Drug Delivery Systems; Electronic Mail; Environment; Flow Cytometry; Grant; Graph; HIV; Human; Imagery; Immune; Immunology; Industry; Inhibitory Concentration 50; Internet; Knowledge; Link; Malignant Neoplasms; Maps; Medicine; Methods; Molecular; Monitor; Mus; Nature; Non-Malignant; Online Systems; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Population; Preclinical Drug Evaluation; Principal Investigator; Publications; Relative (related person); Reporting; Research; Research Personnel; Sampling; Scientist; Screening procedure; Seasons; Signal Pathway; Signal Transduction; Silicon; Small Business Innovation Research Grant; Software Engineering; Source; Specificity; T-Lymphocyte; Technology; Tissue Sample; Tissues; Toxic effect; Universities; Vendor; Visual; analytical tool; base; cancer cell; cancer stem cell; cell type; chemotherapy; data management; data sharing; drug discovery; experience; human disease; in vivo; inhibitor/antagonist; killings; meetings; professor; programs; research study; response; software development; statistics; technology/technique; tool; tumor; web interface

DESCRIPTION (provided by applicant): This project will advance drug discovery by enabling researchers to target pathways and cell subpopulations in primary tissues with greater specificity. Selective targeting of pathways and cell subsets is a critical issue in human disease in fields including cancer and autoimmunity, as increased selectivity can mean the difference between a broad therapy with significant side effects and a focused therapy that selectively targets diseased cells. To meet the growing software needs in the fields of personalized medicine, drug screening, and translational biology, we created Cytobank, a web-based platform for software development, data sharing, and publication of flow cytometry experiment results. We are poised to serve the growing flow cytometry community in a way that no other software can. With Cytobank, a community of users manages experiments like email and shares scientific illustrations like photos in a web 2.0 cloud computing environment. However, missing from this framework currently are tools for single cel drug discovery, including IC50 calculation and display, pathway visualization, and compound screening. We will use the Cytobank web framework for flow cytometry data management and analysis to create a plate based interface for drug screening and build a set of tools that connects key calculations from the big picture view down to the underlying raw single cell data files. The Cytobank Inc. team developed key aspects of the flow cytometry technology, including single cell signaling profiles, fluorescent cell barcoding, and a rapid flow cytometry signaling diagnostic for a human cancer. This SBIR brings together these flow cytometry experts and a team of software engineers to create a tool that will incorporate cell type and pathway information into biochemical assays for drug discovery. This will enable screening for drugs that target cancer cells and not tumor infiltrating T cells and drugs that specifically kill cancer stem cells. This project has significant commercial potential, as the Cytobank flow cytometry data analysis platform is already employed daily by hundreds of users (www.cytobank.org). It has the support of large vendors in the flow cytometry space, biotechnology and pharmaceutical companies, and flow cytometry thought leaders in three clinical research universities. Cytobank's advisory board includes a seasoned technology entrepreneur with over twenty-five years of experience in Silicon Valley and a professor from Stanford University driving both the technology and techniques of applying phosphoflow cytometry. Longer term, the potential of this project is that thousands of scientists around the world will be able to undertake drug discovery in primary samples, comparing the effect of targeted inhibitors of key populations, such as bulk cancer cells, cancer stem cells, and immune cell developmental subsets. In addition to the immediate application in biotechnology industry, this project will also create tools that are useful for basic scientific research." PUBLIC HEALTH RELEVANCE: This project addresses the collaboration and analysis software needs for phosphor-flow cytometry - a molecular technology that is revolutionizing how we understand disease mechanism with broad implications for treatment of human diseases, including HIV, autoimmune disorders, and cancer. By combining knowledge and expertise from wide- ranging disciplines - such as statistics, bioinformatics, biochemistry, immunology and medicine -- this technology has the potential to guide analysis from the basic research phase into disease mechanism, drug discovery, and in vivo monitoring during clinical trials. Cytobank is a web-based platform that enables simple, rapid and efficient communication around phospho-flow cytometry within these disciplines. In this grant, we propose to extend the Cytobank platform by develop web-based analysis suites that will guide drug screening in primary cells by identifying cell type selective compounds and displaying summary-level views that are linked through to rich sources of primary data. Long term, this project will accelerate translational drug discovery by significantly lowering the barrier for researchers to do biochemical studies in tissue samples taken directly from patients.

描述（由申请人提供）：该项目将通过使研究人员能够以更高的特异性靶向主要组织中的通路和细胞亚群来推进药物发现。选择性靶向通路和细胞亚群是包括癌症和自身免疫在内的人类疾病领域的一个关键问题，因为增加的选择性可能意味着具有显著副作用的广泛治疗与选择性靶向病变细胞的集中治疗之间的差异。为了满足个性化医疗、药物筛选和转化生物学领域日益增长的软件需求，我们创建了Cytobank，这是一个基于网络的平台，用于软件开发、数据共享和流式细胞术实验结果的发布。 我们准备以其他软件无法比拟的方式为不断增长的流式细胞术社区提供服务。使用Cytobank，用户社区可以在Web 2.0云计算环境中管理电子邮件等实验，并分享照片等科学插图。然而，该框架目前缺少用于单细胞药物发现的工具，包括IC 50计算和显示，途径可视化和化合物筛选。我们将使用Cytobank网络框架进行流式细胞术数据管理和分析，以创建用于药物筛选的基于板的界面，并构建一组工具，将关键计算从全局视图连接到底层原始单细胞数据文件。 Cytobank Inc.该团队开发了流式细胞术技术的关键方面，包括单细胞信号特征、荧光细胞条形码和用于人类癌症的快速流式细胞术信号诊断。该SBIR汇集了这些流式细胞术专家和软件工程师团队，以创建一个工具，将细胞类型和途径信息纳入药物发现的生化测定中。这将能够筛选靶向癌细胞而不是肿瘤浸润T细胞的药物和特异性杀死癌症干细胞的药物。 该项目具有巨大的商业潜力，因为Cytobank流式细胞术数据分析平台每天都有数百名用户使用（www.cytobank.org）。它得到了流式细胞术领域大型供应商、生物技术和制药公司以及三所临床研究型大学流式细胞术思想领袖的支持。Cytobank的顾问委员会包括一位在硅谷拥有超过25年经验的经验丰富的技术企业家和一位来自斯坦福大学的教授，他推动了磷酸流式细胞术的技术和应用技术。 从长远来看，该项目的潜力在于，全世界成千上万的科学家将能够在原始样本中进行药物发现，比较关键人群的靶向抑制剂的效果，如大量癌细胞，癌症干细胞和免疫细胞发育亚群。除了在生物技术工业中的直接应用外，该项目还将创造对基础科研有用的工具。" 公共卫生关系：该项目解决了磷光体流式细胞术的协作和分析软件需求-这是一种分子技术，它正在彻底改变我们对疾病机制的理解，对人类疾病的治疗具有广泛的影响，包括艾滋病毒，自身免疫性疾病和癌症。通过结合来自广泛学科的知识和专业知识-如统计学，生物信息学，生物化学，免疫学和医学-该技术有潜力指导从基础研究阶段到疾病机制，药物发现和临床试验期间的体内监测的分析。Cytobank是一个基于网络的平台，可以在这些学科中围绕磷酸流式细胞术进行简单，快速和有效的交流。在这项资助中，我们建议通过开发基于网络的分析套件来扩展Cytobank平台，该分析套件将通过识别细胞类型选择性化合物并显示与丰富的原始数据源相关联的摘要级视图来指导原代细胞中的药物筛选。从长远来看，该项目将通过显着降低研究人员在直接从患者身上采集的组织样本中进行生化研究的障碍来加速转化药物的发现。