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

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，以及它们在基因调控和细胞状态测定等重要细胞活动中的功能含义。随着关于基因组高级结构和动力学的新细节的涌入，将需要新的技术来可视化和模拟基因组相互作用的全部范围，以深入了解基因组功能。目前的基因组浏览器专门用于查看初级序列信息。虽然补充信息可以通过新的轨迹进行注释，但在这些浏览器中表示结构层次和交互是相当困难的，特别是在非连续的基因组片段之间。此外，尽管最近有许多努力以各种分辨率和细节测量和建模基因组结构，但很少有工作集中在结合这些模型或利用新的高通量方法产生的大量基因组和表观基因组数据上。为了解决这些问题，该团队创建了一个概念验证交互式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。需要充分利用最新的基因组技术并使其与分析管道集成。虽然已经产生了大量真核生物染色体的空间信息，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，使生物学家能够建立和完善他们自己的3D基因组模型来分析他们的数据。该研究的智力优势包括：1)采用新颖的策略，采用具有强大交互设计元素的新引擎，将原型转换为基于云的3D基因组浏览器，可以在包括web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社区使用。2)增加集成工具，可以分析基因组的三维特征，支持模型构建和验证。3)为定制化数据分析设计并提供健壮的api和脚本。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是实现对基因组功能更全面理解的关键，将为基因组学教学提供新的途径。通过三维可视化来探索基因组将显著推进基因组研究，并将对比较基因组学和遗传学产生深远的影响。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，并形成新的计算方法的基础。该项目为本科生和研究生提供了宝贵的跨学科训练经验，并将吸引更多的学生从事计算生物学的研究。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。

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.