Collaborative Research: CIBR: CloudForest: A Portable Cyberinfrastructure Workflow To Advance Biological Insight from Massive, Heterogeneous Phylogenomic Datasets

跨推断基因树的变异可以说是经验系统基因组学研究中最一致和最引人注目的观察结果，但关于这种变异的原因仍有许多悬而未决的问题。这些问题之所以持续存在，部分原因是现代系统发育推论仍然深受数十年前的范式的影响。来自一个或几个基因的数据通常是同时收集的，合并成一个单一的数据集，并由一个估计共享树的单一程序进行分析。虽然近年来数据集的大小和复杂性发生了根本性的变化，但这种通用工作流的许多方面都是普遍存在的。大多数目前的方法并不自然地整合来自不同来源的推论，无论是不同的研究还是软件，即使是模拟基因历史差异的尖端方法也仍然将这些历史总结为单一的“物种树”拓扑结构。需要更多的通用工具来理解现代基因组数据集固有的异质性。这种多功能性的关键是能够在系统发育工作流程的不同阶段之间灵活而无缝地移动，从推断单个基因树到探索全基因组的系统发育图景，最终了解形成整个基因组变异的生物过程。每个阶段都可能依赖不同的分析工具和软件。这个项目的主要目标是开发一个名为云林的网络基础设施工作流程，以应对系统发育学中的突出挑战，并为研究人员提供一套简化的工具，以探索和理解基因组不同区域的进化史变异(即基因树变异)。云林将允许用户利用各种计算资源，从笔记本电脑到HPC集群，再到基于云的资源，如Jetstream或亚马逊网络服务。云雾森林将满足经验系统遗传学研究的许多突出需求，例如(1)可视化基因树之间的差异，(2)揭示树(森林)集合的结构，(3)对基因树差异的原因进行假设检验，以及(4)检测可能具有外在(和潜在的异常)历史的基因。通过跨计算平台以一致的方式解决这些挑战，云林将使生物学家能够有效地利用他们掌握的任何计算资源，并通过适当的工作流程来解决进化生物学和其他应用领域中各种重要的、悬而未决的问题。该项目还旨在通过以下方式推进更广泛的目标：(1)支持世界各地研究人员在使用先进计算解决方案方面的广泛教育和培训机会，(2)积极促进来自代表性不足群体的研究人员参与计算生物学和取得的成就，(3)为计算机、数学和生物学交叉领域的研究生提供独特的跨学科培训机会，(4)促进开发一个互动和视觉丰富的网站，以学习系统发育和系统基因组学，以及(5)促进将促进人类健康和福祉的应用系统发育研究。这个项目的面向公众的网站可以在https://github.com/jwilgenb/CloudForest.This上找到，该奖项反映了国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Variation across inferred gene trees is arguably the most consistent and striking observation from empirical phylogenomic studies, yet many unanswered questions remain about the causes of this variation. The questions persist in part because modern phylogenetic inference is still deeply influenced by a decades-old paradigm. Data from one or a few genes were typically gathered at the same time, combined into a single dataset, and analyzed by a single program that estimated a shared tree. While the size and complexity of datasets has changed radically in recent years, many aspects of this general workflow pervade. Most current approaches do not naturally integrate inferences from different sources, whether different studies or software packages, and even cutting-edge methods that model differences in gene histories still summarize these histories as a single "species tree" topology. More versatile tools are needed to understand the heterogeneity inherent to modern genomic datasets. Key to this versatility is the ability to flexibly and seamlessly move between different stages of a phylogenetic workflow, from inference of individual gene trees to exploration of the genome-wide phylogenetic landscape and, ultimately, to learning about the biological processes that have shaped variation across the genome. Each of these stages may rely on different analytical tools and software.The major aim of this project is to develop a cyberinfrastructure workflow called Cloudforest to address outstanding challenges in phylogenomics and provide researchers with a set of streamlined tools to explore and understand variation in evolutionary history across different regions of the genome (i.e., gene tree variation). CloudForest will allow users to leverage diverse computing resources that range from laptops, to HPC clusters, to cloud-based resources like JetStream or Amazon Web Services. CloudForest will meet many of the outstanding needs of empirical phylogenomic studies, such as (1) visualizing variation across gene trees, (2) revealing structure in sets of trees (forests), (3) conducting hypothesis tests regarding the causes of gene-tree variation, and (4) detecting genes that may have outlying (and potentially aberrant) histories. By addressing these challenges in a consistent way across computing platforms, CloudForest will allow biologists to make efficient use of any computational resource at their disposal with workflows appropriate for addressing a variety of important, unresolved questions in both evolutionary biology and other applied fields. This project also aims to advance broader goals by (1) supporting broad educational and training opportunities for researchers from around the world in the use of advanced computing solutions, (2) actively promoting the involvement and achievements of researchers from underrepresented groups in computational biology, (3) providing unique, interdisciplinary training opportunities for graduate students at the intersection of computing, math, and biology, (4) contributing to the development of an interactive and visually rich website for learning about phylogenetics and phylogenomics, and (5) facilitating applied phylogenetic research that will advance human health and well-being. A public facing web site for this project can be found at https://github.com/jwilgenb/CloudForest.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.