Enhancement and Cloud Deployment of CaDrA, a software tool for Candidate Driver Analysis of Multiomics Data

CaDrA 的增强和云部署，这是一种用于多组学数据候选驱动程序分析的软件工具

• 批准号: 10406590
• 负责人: MARIA A. KUKURUZINSKA
• 金额: $ 16.39万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406590
• 关键词: Adoption; Age; Alcohol consumption; Attention; Bioconductor; Boston; Code; Communities; Community Integration; Computer software; Custom; Data; Data Set; Dependence; Development; Docking; Documentation; Ensure; Environment; Gender; Gene Expression Profile; General Population; Genetic; Genetic Transcription; Genome; Goals; Grant; Guidelines; Head and Neck Cancer; Human; Image; Journals; Malignant Neoplasms; Manuals; Medicine; Methodology; Methods; Modality; Modeling; Molecular; Motivation; Multiomic Data; National Institute of Dental and Craniofacial Research; Online Systems; Output; Pathway interactions; Publications; Publishing; Race; Readiness; Reproducibility; Research; Research Support; Running; Sampling; Sensitivity and Specificity; Services; Smoking Status; Software Engineering; Software Tools; Spottings; Standardization; Structure; Tars; Techniques; Testing; Text; The Cancer Genome Atlas; Time; Universities; Visualization; Work; base; beta catenin; computerized tools; design; frontier; graphical user interface; improved; in silico; interest; molecular phenotype; mouse model; multiple omics; open source; parent grant; portability; prototype; response; single-cell RNA sequencing; tool; transcriptome sequencing; user centered design; user-friendly

We aim to further develop, optimize, document, containerize and deliver as an R package CaDrA (Candidate Driver Analysis), an open-source, user-friendly computational tool for the analyses of cancer multi-omics datasets. A prototype of the package already exists, and was applied in studies published in high-impact journals. The under- lying methodology was evaluated with simulated and real data, and it was shown to have high sensitivity and specificity. The methodology was developed in part under the auspices of a NIDCR-sponsored F31 (awardee, Vinay Kartha), with the associated publications receiving considerable attention, and we received several requests to share the code and clarify its use. We plan to utilize this analytical approach in the context of our parent grant (NIDCR MPI 1R01DE030350-01A1), aimed at investigating, through experimental and in-silico approaches, the β- catenin/CBP axis in head and neck cancer. An expanded and optimized tool will support the analysis of bulk and single cell RNAseq data we are generating as part of that grant, as well as the querying of public datasets, such as TCGA, CPTAC, CCLE and others, based on transcriptional signatures derived from our own generated data. While some analysis methods that can integrate and interpret multiple experimental and molecular data types exist, they tend to either provide for highly interactive interfaces but relatively basic analytic functionalities, or for sophisticated analysis methods not adequately supported by well-documented and user-friendly tools. Our proposed tool occupies the “sweet spot” in between and will provide for advanced statistical techniques, a user- friendly interface, and a well-documented, open-source R package, which will be available to the research community as a stand-alone tool, or “integratable” into other tools and analytical workflows, and will facilitate reproducibility and transparency of the analyses performed. To facilitate the tool’s wider adoption, applicability, and scalability, its robustness, portability, and user-friendliness need to be enhanced. This proposal would allow us to pursue it extension with new functionalities, its enhancement and optimization, documentation, and containerization into an open-source package made available through GitHub, and installable through CRAN or Bioconductor. Our work plan includes extension of the statistical functionalities supported, code cleaning, profiling, testing and optimization to improve run-time efficiency, adoption of data structures and constructs compliant with Bioconductor guidelines, packaging to ensure easy code installation and testing, containerization to support cloud deployment, development of a graphical interface to increase the tool’s user-friendliness, and design of a web- based lending page to be hosted on our university server. Relevance and Impact. Availability of the tool will be instrumental to the pursuit of our parent grant aims. In parti- cular, it will support the analysis of our own generated bulk and single cell RNAseq data from mouse models and human samples. R packaging and containerization will also facilitate adoption by the research community.

我们的目标是进一步开发、优化、记录、包装并作为R包CADRA(候选驱动程序)交付 分析)，这是一个开源的、用户友好的计算工具，用于分析癌症多组学数据集。一个 该包的原型已经存在，并被应用于发表在高影响力期刊上的研究。下面的- 用模拟数据和真实数据对测谎方法进行了评估，结果表明该方法具有较高的灵敏度和可信度。 专一性。该方法部分是在NIDCR赞助的F31(获奖者，Vinay)的赞助下开发的 Kartha)，相关出版物受到了相当大的关注，我们收到了几个请求 分享代码并阐明其用途。我们计划在母公司赠款的背景下使用这种分析方法 (NIDCR MPI 1R01DE030350-01A1)，旨在通过实验和硅胶方法研究β- 头颈癌中的连环蛋白/CBP轴扩展和优化的工具将支持批量和 作为拨款一部分生成的单细胞RNAseq数据，以及对公共数据集的查询，例如 TCGA、CPTAC、CCLE和其他，基于来自我们自己生成的数据的转录签名。 虽然存在一些可以集成和解释多种实验和分子数据类型的分析方法， 它们倾向于提供高度交互的界面但相对基本的分析功能，或者 复杂的分析方法没有得到文件充分记录和用户友好的工具的充分支持。我们的 拟议的工具占据了介于两者之间的“甜蜜点”，并将提供先进的统计技术，用户- 友好的界面，以及一个文档齐全的开源R包，将可用于研究 社区作为一个独立的工具，或“可集成”到其他工具和分析工作流程中，并将促进 分析的重复性和透明度。 为了促进该工具的广泛采用、适用性和可伸缩性，它的健壮性、可移植性和用户友好性 需要加强。这项提议将使我们能够扩展它，增加新的功能，增强它 以及优化、文档编制和集装化到一个开放源码包中，可通过 GitHub，可通过CRAN或BioConductor安装。 我们的工作计划包括扩展所支持的统计功能、代码清理、性能分析、测试和 优化以提高运行时效率，采用符合以下要求的数据结构和构造 BioConductor指南、确保轻松代码安装和测试的包装、支持云的集装化 部署，开发图形界面以增加该工具的用户友好性，并设计一个网络- 基于借贷页面将在我们的大学服务器上托管。 相关性和影响力。该工具的提供将有助于实现我们的母公司赠款目标。第三部分-- ，它将支持分析我们自己从小鼠模型和 人体样本。R包装和集装箱化也将促进研究界的采用。