III: AF: Medium: Collaborative Research: Enabling Phylogenetic Inference for Modern Data Sets

III：AF：媒介：协作研究：为现代数据集启用系统发育推断

• 批准号: 1564137
• 负责人: Frederick Matsen
• 金额: $ 82.49万
• 依托单位: Fred Hutchinson Cancer Research Center
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1564137&HistoricalAwards=false
• 关键词: III; AF; Medium; Collaborative; Research

Many important subjects in biological and biomedical research require a robust means of phylogenetic tree inference: for models of viral transmission, for gene function inference, and for assessment of genetic diversity in the human microbiome, to name a few. These applications also depend on a rigorous means of assessing tree inference uncertainty; the Bayesian framework provides a principled means of assessing and integrating out this uncertainty. The currently available Bayesian algorithmic tools are not capable of performing inferences on large modern data sets, which also may be continually changing as new sequencing results become available. In particular, state-of-the-art methods are almost exclusively based on random-walk Markov chain Monte Carlo (MCMC) using uniformly selected local moves, even though most of these local moves will substantially worsen even a mediocre tree. Convergence problems with this approach are well documented, and thus current methods are limited to around 1000 sequences, a number much smaller than the size of microbial and immune data sets relevant to modern biomedicine. In addition, all current methods require inference to be started from scratch each time the sequence data changes. The broader impacts of this work will extend in three directions: enabling novel applications of Bayesian phylogenetics, stimulating new areas of computer science research, and attracting new talent to the field.Applications of phylogenetics, in particular Bayesian phylogenetics, are being significantly held back by computational limitations. High-throughput sequencing technologies can return millions of sequences for studies of the human microbiome, viruses, oceanic microbes and antibody-making B Cells but theses cannot be handled with current methods. The models also need to be more realistic, without assumptions of independent interactions. Understanding the shape of multidimensional phylogenetic likelihood surfaces in detail might help to improve the topology. The teams will also investigate when an optimal tree on a taxon sets contains the optimal tree on a taxon subset. These will help to expand the approach to phylogenetic inference. These algorithmic insights will be incorporated into publicly available inference packages with a goal to provide inference on an order of magnitude more taxa than currently possible.

生物学和生物医学研究中的许多重要课题需要强大的系统发育树推断方法：病毒传播模型、基因功能推断以及人类微生物组遗传多样性评估等。这些应用程序还依赖于评估树推理不确定性的严格方法；贝叶斯框架提供了一种评估和整合这种不确定性的原则方法。当前可用的贝叶斯算法工具无法对大型现代数据集进行推理，随着新的测序结果的出现，这些数据集也可能会不断变化。特别是，最先进的方法几乎完全基于使用统一选择的局部移动的随机游走马尔可夫链蒙特卡罗（MCMC），尽管这些局部移动中的大多数即使是平庸的树也会大大恶化。这种方法的收敛问题已有详细记录，因此当前的方法仅限于大约 1000 个序列，这个数字远小于与现代生物医学相关的微生物和免疫数据集的大小。此外，当前所有方法都需要在每次序列数据发生变化时从头开始推理。这项工作的更广泛影响将延伸到三个方向：推动贝叶斯系统发育学的新颖应用、刺激计算机科学研究的新领域以及吸引新人才进入该领域。系统发育学的应用，特别是贝叶斯系统发育学，正受到以下因素的严重阻碍：计算限制。 高通量测序技术可以返回数百万个序列，用于人类微生物组、病毒、海洋微生物和抗体制造 B 细胞的研究，但目前的方法无法处理这些数据。 模型还需要更加现实，而不需要独立交互的假设。 详细了解多维系统发育似然面的形状可能有助于改进拓扑。 该团队还将调查分类单元集上的最优树何时包含分类单元子集上的最优树。 这些将有助于扩展系统发育推断的方法。这些算法见解将被纳入公开可用的推理包中，目标是提供比目前多一个数量级的分类单元的推理。