III: Medium: Collaborative Research: Developing a 3D Browser to Explore Genomes

III：媒介：协作研究：开发 3D 浏览器来探索基因组

• 批准号: 1161586
• 负责人: Jijun Tang
• 金额: $ 44.43万
• 依托单位: University South Carolina Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1161586&HistoricalAwards=false
• 关键词: III; Medium; Collaborative; Research; Developing

New genome technologies enabled us to analyze the spatial conformation and interaction of chromatin together with their functional implication in important cellular activities such as gene regulation and cell state determination. With the influx of new details about the higher-level structure and dynamics of the genome, novel techniques will be required to visualize and model the full extent of genomic interactions to gain insight about genome functions. Current genome browsers are specifically aimed at viewing primary sequence information. Although supplemental information can be annotated via new tracks, representing structural hierarchies and interactions is quite difficult in these browsers, particularly across non-contiguous genomic segments. In addition, in spite of many recent efforts to measure and model the genome structure at various resolutions and detail, little work has focused on combining these models or taken advantage of the large amount of genomic and epigenomic data generated from new high-throughput approaches. To address these issues, the team has created a proof-of-concept interactive 3D viewer, Genome3D, to enable integration and visualization of genomic and epigenomic data in three dimension. Substantial development is needed to take advantage of the newest genomic technologies and to enable its integration with analysis pipelines. While enormous amount of spatial information for eukaryotic chromosomes have been generated, the size and complexity of these data require the design and development of new algorithms and methods in data integration and model construction. The goal is to develop a full-fledged, platform independent system that enables biologists to build and refine their own 3D genome models to analyze their data. The intellectual merits of the research include: 1) Implementing a novel strategy to employ new engines with strong interactive design element to transform the prototype into a cloud-based 3D genome browser that can be used on various platforms including web browsers and tablets, making 3D structural genome information available to a broader research community. 2) Adding integrated tools that can analyze 3D features of genomes and support model building and validation. 3) Designing and providing robust set of APIs and scripting for customized data analysis. 4) Collaborating with other researchers to explore and visualize new three dimensional genome models.There are a number of broader impacts in this research. A multi-scale three dimensional genome browser is crucial to achieve fuller understanding of genome functions and will provide a new way to teach genomics. Exploring genomes through 3D visualization will significantly advance genome research and will have a profound impact on comparative genomics and genetics. The use of new user interaction-intensive engines into scientific research tools and will encourage researchers in every area to use interactive visualization to analyze data. New algorithms to analyze models and visualize genomic information can be extended to problems of similar size in other fields and form the basis for new computational approaches. This project provides valuable interdisciplinary training experiences to undergraduate and graduate students and will attract more students to computational biology research. Results and the new browser will be disseminated through publications, workshops and tutorials and will enable customized development by providing detailed APIs and tutorials.

新的基因组技术使我们能够分析染色质的空间构象和相互作用及其在重要细胞活动（例如基因调控和细胞状态确定）中的功能含义。随着有关基因组高级结构和动力学的新细节的涌入，将需要新技术来可视化和建模基因组相互作用的全部范围，以深入了解基因组功能。 当前的基因组浏览器专门用于查看一级序列信息。 尽管可以通过新轨道注释补充信息，但在这些浏览器中表示结构层次结构和交互相当困难，特别是在不连续的基因组片段中。 此外，尽管最近做出了许多努力以各种分辨率和细节测量和建模基因组结构，但很少有工作集中于组合这些模型或利用新的高通量方法生成的大量基因组和表观基因组数据。为了解决这些问题，该团队创建了一个概念验证的交互式 3D 查看器 Genome3D，以实现基因组和表观基因组数据的三维集成和可视化。 需要进行实质性的开发才能利用最新的基因组技术并使其与分析流程集成。 虽然真核染色体的大量空间信息已经产生，但这些数据的规模和复杂性要求在数据集成和模型构建方面设计和开发新的算法和方法。目标是开发一个成熟的、独立于平台的系统，使生物学家能够构建和完善自己的 3D 基因组模型来分析他们的数据。 该研究的智力优点包括：1）实施新颖的策略，采用具有强大交互设计元素的新引擎，将原型转变为基于云的3D基因组浏览器，可在包括网络浏览器和平板电脑在内的各种平台上使用，使3D结构基因组信息可供更广泛的研究界使用。 2）添加可以分析基因组3D特征并支持模型构建和验证的集成工具。 3) 设计并提供一组强大的 API 和脚本以进行定制数据分析。 4）与其他研究人员合作探索和可视化新的三维基因组模型。这项研究有许多更广泛的影响。 多尺度三维基因组浏览器对于更全面地了解基因组功能至关重要，并将提供一种教授基因组学的新方法。 通过 3D 可视化探索基因组将显着推进基因组研究，并对比较基因组学和遗传学产生深远影响。在科学研究工具中使用新的用户交互密集型引擎，将鼓励各个领域的研究人员使用交互式可视化来分析数据。 分析模型和可视化基因组信息的新算法可以扩展到其他领域类似规模的问题，并构成新计算方法的基础。该项目为本科生和研究生提供了宝贵的跨学科培训经验，并将吸引更多学生从事计算生物学研究。 结果和新浏览器将通过出版物、研讨会和教程进行传播，并将通过提供详细的 API 和教程来实现定制开发。