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Warnow, T.

Publications and source records attributed to Warnow, T..

26 records · Page 2Linked to original sources

An improved mode of running PASTA

PASTA is a method for estimating alignments and trees that has been able to provide excellent accuracy on large sequence datasets. By design, PASTA operates using iteration, in which the tree from the previous iteration is used to inform a divide-and-conquer strategy during which a new alignment is computed on the sequence dataset, and then a new maximum likelihood tree is estimated on the new alignment. In its default setting, PASTA runs for three iterations and returns that alignment/tree pair from the last iteration. Here we use both biological and simulated nucleotide datasets to show that returning the alignment/tree pair that has the best maximum likelihood score improves on the default usage.

bioinformatics↗

Advancing Divide-and-Conquer Phylogeny Estimation

One of the Grand Challenges in Science is the construction of the Tree of Life, an evolutionary tree containing several million species, spanning all life on earth. However, the construction of the Tree of Life is enormously computationally challenging, as all the current most accurate methods are either heuristics for NP-hard optimization problems or Bayesian MCMC methods that sample from tree space. One of the most promising approaches for improving scalability and accuracy for phylogeny estimation uses divide-and-conquer: a set of species is divided into overlapping subsets, trees are constructed on the subsets, and then merged together using a "supertree method". Here, we present Exact-RFS-2, the first polynomial-time algorithm to find an optimal supertree of two trees, using the Robinson-Foulds Supertree (RFS) criterion (a major approach in supertree estimation that is related to maximum likelihood supertrees), and we prove that finding the RFS of three input trees is NP-hard. We also present GreedyRFS (a greedy heuristic that operates by repeatedly using Exact-RFS-2 on pairs of trees, until all the trees are merged into a single supertree). We evaluate Exact-RFS-2 and GreedyRFS, and show that they have better accuracy than the current leading heuristic for RFS. Exact-RFS-2 and GreedyRFS are available in open source form on Github at github.com/yuxilin51/GreedyRFS.

bioinformatics↗

FastMulRFS: Statistically consistent polynomial time species tree estimation under gene duplication

MotivationSpecies tree estimation is a basic part of biological research but can be challenging because of gene duplication and loss (GDL), which results in genes that can appear more than once in a given genome. All common approaches in phylogenomic studies either reduce available data or are error-prone, and thus, scalable methods that do not discard data and have high accuracy on large heterogeneous datasets are needed. ResultsWe present FastMulRFS, a polynomial-time method for estimating species trees without knowledge of orthology. We prove that FastMulRFS is statistically consistent under a generic model of GDL when adversarial GDL does not occur. Our extensive simulation study shows that FastMulRFS matches the accuracy of MulRF (which tries to solve the same optimization problem) and has better accuracy than prior methods, including ASTRAL-multi (the only method to date that has been proven statistically consistent under GDL), while being much faster than both methods. AvailabilityFastMulRFS is available on Github (https://github.com/ekmolloy/fastmulrfs).

evolutionary biology↗

Unblended Disjoint Tree Merging using GTM improves species tree estimation

Phylogeny estimation is an important part of much biological research, but large-scale tree estimation is infeasible using standard methods due to computational issues. Recently, an approach to large-scale phylogeny has been proposed that divides a set of species into disjoint subsets, computes trees on the subsets, and then merges the trees together using a computed matrix of pairwise distances between the species. The novel component of these approaches is the last step: Disjoint Tree Merger (DTM) methods. We present GTM (Guide Tree Merger), a polynomial time DTM method that adds edges to connect the subset trees, so as to provably minimize the topological distance to a computed guide tree. Thus, GTM performs unblended mergers, unlike the previous DTM methods. Yet, despite the potential limitation, our study shows that GTM has excellent accuracy, generally matching or improving on two previous DTMs, and is much faster than both. Thus, the GTM approach to the DTM problem is a useful new tool for large-scale phylogenomic analysis, and shows the surprising potential for unblended DTM methods. The software for GTM is available at https://github.com/vlasmirnov/GTM.

evolutionary biology↗

Polynomial-Time Statistical Estimation of Species Trees under Gene Duplication and Loss

Phylogenomics--the estimation of species trees from multilocus datasets--is a common step in many biological studies. However, this estimation is challenged by the fact that genes can evolve under processes, including incomplete lineage sorting (ILS) and gene duplication and loss (GDL), that make their trees different from the species tree. In this paper, we address the challenge of estimating the species tree under GDL. We show that species trees are identifiable under a standard stochastic model for GDL, and that the polynomial-time algorithm ASTRAL-multi, a recent development in the ASTRAL suite of methods, is statistically consistent under this GDL model. We also provide a simulation study evaluating ASTRAL-multi for species tree estimation under GDL. All scripts and datasets used in this study are available on the Illinois Data Bank: https://doi.org/10.13012/B2IDB-2626814_V1.

evolutionary biology↗

Statistically consistent divide-and-conquer pipelines for phylogeny estimation using NJMerge

BackgroundDivide-and-conquer methods, which divide the species set into over-lapping subsets, construct a tree on each subset, and then combine the subset trees using a supertree method, provide a key algorithmic framework for boosting the scalability of phylogeny estimation methods to large datasets. Yet the use of supertree methods, which typically attempt to solve NP-hard optimization problems, limits the scalability of such approaches.\n\nResultsIn this paper, we introduce a divide-and-conquer approach that does not require supertree estimation: we divide the species set into pairwise disjoint subsets, construct a tree on each subset using a base method, and then combine the subset trees using a distance matrix. For this merger step, we present a new method, called NJMerge, which is a polynomial-time extension of Neighbor Joining (NJ); thus, NJMerge can be viewed either as a method for improving traditional NJ or as a method for scaling the base method to larger datasets. We prove that NJMerge can be used to create divide-and-conquer pipelines that are statistically consistent under some models of evolution. We also report the results of an extensive simulation study evaluating NJMerge on multi-locus datasets with up to 1000 species. We found that NJMerge sometimes improved the accuracy of traditional NJ and substantially reduced the running time of three popular species tree methods (ASTRAL-III, SVDquartets, and \"concatenation\" using RAxML) without sacrificing accuracy. Finally, although NJMerge can fail to return a tree, in our experiments, NJMerge failed on only 11 out of 2560 test cases.\n\nConclusionsTheoretical and empirical results suggest that NJMerge is a valuable technique for large-scale phylogeny estimation, especially when computational resources are limited. NJMerge is freely available on Github (http://github.com/ekmolloy/njmerge).

evolutionary biology↗

Benchmarking Statistical Multiple Sequence Alignment

The estimation of multiple sequence alignments of protein sequences is a basic step in many bioinformatics pipelines, including protein structure prediction, protein family identification, and phylogeny estimation. Statistical co-estimation of alignments and trees under stochastic models of sequence evolution has long been considered the most rigorous technique for estimating alignments and trees, but little is known about the accuracy of such methods on biological benchmarks. We report the results of an extensive study evaluating the most popular protein alignment methods as well as the statistical co-estimation method BAli-Phy on 1192 protein data sets from established benchmarks as well as on 120 simulated data sets. Our study (which used more than 230 CPU years for the BAli-Phy analyses alone) shows that BAli-Phy is dramatically more accurate than the other alignment methods on the simulated data sets, but is among the least accurate on the biological benchmarks. There are several potential causes for this discordance, including model misspecification, errors in the reference alignments, and conflicts between structural alignment and evolutionary alignments; future research is needed to understand the most likely explanation for our observations. multiple sequence alignment, BAli-Phy, protein sequences, structural alignment, homology

bioinformatics↗

To include or not to include: The impact of gene filtering on species tree estimation methods

Species tree estimation from loci sampled from multiple genomes is now common, but is challenged by the heterogeneity across the genome due to multiple processes, such as gene duplication and loss, horizontal gene transfer, and incomplete lineage sorting. Although methods for estimating species trees have been developed that address gene tree heterogeneity due to incomplete lineage sorting, many of these methods operate by combining estimated gene trees and are hence vulnerable to gene tree quality. There is also the added concern that missing data, which is frequently encountered in genome-scale datasets, will impact species tree estimation.\n\nOur study addresses the impact of gene filtering on species trees inferred from multi-gene datasets. We address these questions using a large and heterogeneous collection of simulated datasets both with and without missing data. We compare several established coalescent-based methods (ASTRAL, ASTRID, MP-EST, and SVDquartets within PAUP*) as well as unpartitioned concatenation using maximum likelihood (RAxML).\n\nOur study shows that gene tree error and missing data impact all methods (and some methods degrade more than others), but the degree of incomplete lineage sorting and gene tree estimation error impacts the absolute and relative performance of methods as well as their response to gene filtering strategies. We find that filtering genes based on the degree of missing data is either neutral or else reduces the accuracy of all five methods examined, and so is not recommended. Filtering genes based on gene tree estimation error shows somewhat different trends. Under low levels of incomplete lineage sorting, removing genes with high gene tree estimation error can improve the accuracy of summary methods, but only if not too many genes are removed. Otherwise, filtering genes tends to increase error, especially under high levels of incomplete lineage sorting. Hence, while filtering genes based on missing data is not recommended, there are conditions under which removing high error gene trees can improve species tree estimation. This study provides insights into prior studies and suggests approaches for analyzing phylogenomic datasets.

evolutionary biology↗