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确定等重要细胞活动中的功能含义。随着关于基因组更高层次结构和动态的新细节的涌入，将需要新的技术来可视化和建模基因组相互作用的全部范围，以获得对基因组功能的洞察。目前的基因组浏览器专门针对查看初级序列信息。虽然补充信息可以通过新的轨道进行注释，但在这些浏览器中表示结构层次和相互作用是相当困难的，特别是跨不连续的基因组片段。此外，尽管最近做出了许多努力，以不同的分辨率和细节测量基因组结构并对其进行建模，但很少有工作侧重于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。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。要利用最新的基因组技术并使其能够与分析管道相结合，需要进行实质性的开发。虽然已经产生了海量的真核染色体空间信息，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。其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他们自己的3D基因组模型，以分析他们的数据。这项研究的智力价值包括：1)实施了一种新的战略，采用具有强大交互设计元素的新引擎，将原型转化为基于云的3D基因组浏览器，可以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社区使用。2)增加了能够分析基因组三维特征、支持建模和验证的集成工具。3)设计并提供一套强大的API和脚本，用于定制数据分析。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。一个多尺度的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，并将为基因组学教学提供一种新的方式。通过三维可视化探索基因组将极大地推动基因组研究，并将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中类似规模的问题，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培训经验，并将吸引更多的学生从事计算生物学研究。结果和新的浏览器将通过出版物、讲习班和教程传播，并将通过提供详细的API和教程实现定制开发。

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.