Multi-Scale Modeling of Vascular Signaling Units

项目摘要/摘要 高血压是心血管疾病最大的可改变的危险因素之一，这是 导致男性和女性死亡的主要原因。随着更多的抗高血压疗法变得 但很明显，男性和女性对这些治疗的反应是不同的。 然而，这些性别差异背后的机制在很大程度上是未知的。家长赠款的目的是 发展多学科方法来揭示男性和女性高血压的发病机制 通过建立一个详细的模型来预测药物如何不同地改变血管功能 在这些群体之间。这是通过比较男性和女性的血管顺畅来实现的 肌肉细胞使用一系列最先进的技术，包括电生理，钙离子 成像，纳米级超分辨率显微镜，并在电子预测模型中详细介绍。这个 此补充项目的目标是提供可靠、可重现和可扩展的分析 将统一这些固有的多模式数据集的软件。这些分析管道的输出 将被用作计算模型的输入，以确保对关键字的可靠的地面真相预测 生物物理参数。每个软件组件都将有一个完整记录的后端引擎 具有用于互操作性的高级编程接口(API)， 可扩展性，并可被其他人采用。基于云的计算和图形用户界面 (图形用户界面)将被开发。这些分析管道将通过使用工程技术进行加固 版本控制、单元测试、代码文档以及与现有 软件。为了让其他人可以访问和使用这些工具，我们将使用商定的文件格式 和生物命名标准。为了让这些管道可被发现，它们将是 可通过多种渠道访问，包括在线开放源代码共享和安装 从包管理器那里。为了确保其他研究人员一键访问，管道将 集装箱化，便于可靠安装，允许在个人计算机上运行相同的代码 计算机、本地群集或云中。通过遵循最佳的软件工程原则，我们的目标是 创建可无缝促进小组之间协作的多模式分析管道 并允许与更多的科学研究人员共享和发布数据和分析 社区，最终是公众。

Project Summary/Abstract Hypertension is one of the largest modifiable risk factors for cardiovascular disease, which is the leading cause of mortality for men and women. As more antihypertensive therapies become available, it has become clear that males and females respond differently to these treatments. Yet the mechanisms behind these sex differences are largely unknow. The parent grant aims to develop a multi-disciplinary approach to reveal the mechanisms of male and female hypertension and by building a detailed model to predict how drugs can differentially alter vascular function between these groups. This is being achieved by comparing male and female vascular smooth muscle cells using a range of state-of-the-art techniques including electrophysiology, Ca2+ imaging, nano-scale super-resolution microscopy, and detailed in silico predictive modelling. The goals of this supplemental project is to provide reliable, reproducible, and extensible analysis software that will unify these inherent multi-modal data sets. The output of these analysis pipelines will be used as input to computational models to ensure robust ground-truth predictions of key biophysical parameters. Each software component will have a fully documented back-end engine (written in Python) with an advanced-programming-interface (API) for interoperability, extendibility, and adoption by others. Cloud based computational and graphical-user-interfaces (GUIs) will be developed. These analysis pipelines will be hardened by using engineering standards for versioning, unit testing, code documentation, and interoperability with existing software. For these tools to be accessible and used by others, we will use agreed upon file formats and biological nomenclature standards. For these pipelines to be discoverable, they will be accessibility through multiple channels including online open-source code sharing and installation from package managers. To ensure one-click access for other researchers, the pipelines will be containerized for easy and reliable installation, allowing the same code to be run on individual computers, local cluster, or in the cloud. By following best software engineering principles, we aim to create a multi-modal analysis pipeline that seamlessly facilitate collaborations between groups of researchers and allow the sharing and publishing of data and analysis with the greater scientific community and ultimately the public.