Lost in Tree Space (LiTS)

我们建议对两种现象进行研究，这两种现象可能会让我们在进行系统发育推理时迷失在树的空间中。一个是基因树与物种树的不协调，需要协调，第二个现象是树空间中存在梯田，需要进一步审查。因此，我们的首要目标是进行研究，以更好地了解我们为什么迷失在树空间中，以及如何以更有针对性和计算效率的方式更好地在树空间中导航。我们建议的具体项目是建立在前两个资助期两个实验室之间非常成功的合作以及通过前一笔资助金资助的初级研究人员各自积累的经验的基础上的。更具体地说，我们将开发方法和算法，并将它们作为开源工具用于(I)采样、枚举和总结树空间中的梯田上的树，(Ii)在存在梯田的情况下以最大似然和简约性更有效地搜索树空间和评估树拓扑，以及(Iii)进行可扩展、高效和准确的基因树物种树协调。生物学意义：我们工作的生物学意义被以下事实所突显：仅有几种易于使用的基于似然的基因树物种树协调工具存在。尽管我们目前只有一个GeneRax的原型实现，缺乏许多理想的功能，但它已经被一些早期采用者使用。考虑到RAxML-NG和IQ-TREE的庞大用户基础，它们在搜索效率上的每一次改进都意味着可以节省数千个CPU小时。此外，如(Dobrin，Zwickl，and Sanderson 2018)所示，目前过多的系统基因组数据集包含梯田。换句话说，这不是搜索空间的奇异理论属性，而是经验数据的实际问题，需要解决和更好地研究。如果我们关于准阶地的初步发现得到证实，阶地的存在将影响更大比例的经验系统发育分析，因为梯田状结构的出现将不依赖于特定的分支连接模式。由于梯田是在缺失序列的情况下出现的，人们可以假设，对完整的基因组进行测序将完全解决这个问题。然而，情况并非如此。由于物种的生物多样性和基因的缺失导致并不是所有的基因都存在于所有的生物体中，因此缺失的序列是大型系统基因组比对的固有特性。因此，缺失的数据仍然是一个重要的问题，需要系统地解释系统基因组学软件。如果我们试图解决包含极其多样化的物种和包含不同基因集合的基因组的生命之树，这一点尤其重要。

We propose to conduct research on two phenomena that can get us lost in tree space when conducting phylogenetic inferences. One is that of gene tree versus species tree discordance that requires reconciliation and the second phenomenon is the existence of terraces in tree spaces requiring further scrutiny. Thus, our overarching goal is to conduct research to better understand why we are lost in tree space and how we can better navigate through tree space in a more targeted as well as computationally efficient manner. The specific projects, we propose build upon the highly successful collaboration between the two labs from the two preceding funding periods as well as on the respective experience accumulated by the junior researchers that were funded through the preceding grant. More specifically, we will develop methods and algorithms and make them available as open source tools to (i) sample, enumerate, and summarize trees residing on a terrace in tree space, (ii) more efficiently search tree space and evaluate tree topologies in the presence of terraces under maximum likelihood and parsimony, and (iii) conduct scalable, efficient, and accurate gene tree species tree reconciliations. Biological significance: The biological significance of our work is underlined by the fact that only a handful of easy to use likelihood-based gene tree species tree reconciliation tools exist. Despite the fact, that we only have a prototype implementation of GeneRax available at present that lacks numerous desirable features, it is already being used by some early adopters. Given the large user base of RAxML-NG and IQ-TREE, every improvement in their search efficiency means that thousands of CPU hours can be saved. In addition, as shown in (Dobrin, Zwickl, and Sanderson 2018) a plethora of current phylogenomic datasets contains terraces. In other words, this is not an exotic theoretical property of search spaces, but a real problem with empirical data that needs to be addressed and better studied. If our initial findings on quasi-terraces are confirmed the existence of terraces will affect a substantially larger fraction of empirical phylogenetic analyses as the occurrence of terrace-like structures will not depend on a specific branch linkage model. As terraces occur in the presence of missing sequences one could assume that sequencing complete genomes would solve the problem entirely. However, this is not the case. Since biological diversity of species and gene deletions are responsible for the fact that not all of the genes are present in all organisms, missing sequences are inherent property of large phylogenomic alignments. Therefore, missing data remains an important issue to be systematically accounted for by phylogenomic software. This is specially important if we attempt to resolve the Tree of Live comprising extremely diverse species with genomes containing different collections of genes.