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22 Publications visible to you, out of a total of 22

Abstract (Expand)

Maximum Likelihood (ML) based phylogenetic inference constitutes a challenging optimization problem. Given a set of aligned input sequences, phylogenetic inference tools strive to determine the treerive to determine the tree topology, the branch-lengths, and the evolutionary parameters that maximize the phylogenetic likelihood function. However, there exist compelling reasons to not push optimization to its limits, by means of early, yet adequate stopping criteria. Since input sequences are typically subject to stochastic and systematic noise, one should exhibit caution regarding (over-)optimization and the inherent risk of overfitting the model to noisy input data. To this end, we propose, implement, and evaluate four statistical early stopping criteria in RAxML-NG that evade excessive and compute-intensive (over-)optimization. These generic criteria can seamlessly be integrated into other phylo-genetic inference tools while not decreasing tree accuracy. The first two criteria quantify input data-specific sampling noise to derive a stopping threshold. The third, employs the Kishino-Hasegawa (KH) test to statistically assess the significance of differences between intermediate trees before , and after major optimization steps in RAxML-NG. The optimization terminates early when improvements are insignificant. The fourth method utilizes multiple testing correction in the KH test. We show that all early stopping criteria infer trees that are statistically equivalent compared to inferences without early stopping. In conjunction with a necessary simplification of the standard RAxML-NG tree search heuristic, the average inference times on empirical and simulated datasets are ∼3.5 and ∼1.8 times faster, respectively, than for standard RAxML-NG v.1.2. The four stopping criteria have been implemented in RAxML-NG and are available as open source code under GNU GPL at https://github.com/togkousa/raxml-ng .

Authors: Anastasis Togkousidis, Alexandros Stamatakis, Olivier Gascuel

Date Published: 8th Jul 2024

Publication Type: Journal

Abstract (Expand)

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method, and the choice of genomic regions 1–3. Here, we address these issues by analyzing genomes of 363 bird species 4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a remarkable degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous–Paleogene (K–Pg) boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that challenge modeling due to extreme GC content, variable substitution rates, incomplete lineage sorting, or complex evolutionary events such as ancient hybridization. Assessment of the impacts of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates, and relative brain size following the K–Pg extinction event, supporting the hypothesis that emerging ecological opportunities catalyzed the diversification of modern birds. The resulting phylogenetic estimate offers novel insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

Authors: Josefin Stiller, Shaohong Feng, Al-Aabid Chowdhury, Iker Rivas-González, David A. Duchêne, Qi Fang, Yuan Deng, Alexey Kozlov, Alexandros Stamatakis, Santiago Claramunt, Jacqueline M. T. Nguyen, Simon Y. W. Ho, Brant C. Faircloth, Julia Haag, Peter Houde, Joel Cracraft, Metin Balaban, Uyen Mai, Guangji Chen, Rongsheng Gao, Chengran Zhou, Yulong Xie, Zijian Huang, Zhen Cao, Zhi Yan, Huw A. Ogilvie, Luay Nakhleh, Bent Lindow, Benoit Morel, Jon Fjeldså, Peter A. Hosner, Rute R. da Fonseca, Bent Petersen, Joseph A. Tobias, Tamás Székely, Jonathan David Kennedy, Andrew Hart Reeve, Andras Liker, Martin Stervander, Agostinho Antunes, Dieter Thomas Tietze, Mads Bertelsen, Fumin Lei, Carsten Rahbek, Gary R. Graves, Mikkel H. Schierup, Tandy Warnow, Edward L. Braun, M. Thomas P. Gilbert, Erich D. Jarvis, Siavash Mirarab, Guojie Zhang

Date Published: 1st Apr 2024

Publication Type: Journal

Abstract (Expand)

Motivation: Genotype datasets typically contain a large number of single nucleotide polymorphisms for a comparatively small number of individuals. To identify similarities between individuals and to infer an individual’s origin or membership to a cultural group, dimensionality reduction techniques are routinely deployed. However, inherent (technical) difficulties such as missing or noisy data need to be accounted for when analyzing a lower dimensional representation of genotype data, and the uncertainty of such an analysis should be reported in all studies. However, to date, there exists no stability estimation technique for genotype data that can estimate this uncertainty. Results: Here, we present Pandora, a stability estimation framework for genotype data based on bootstrapping. Pandora computes an overall score to quantify the stability of the entire embedding, perindividual support values, and deploys a k-means clustering approach to assess the uncertainty of assignments to potential cultural groups. In addition to this bootstrap-based stability estimation, Pandora offers a sliding-window stability estimation for whole-genome data. Using published empirical and simulated datasets, we demonstrate the usage and utility of Pandora for studies that rely on dimensionality reduction techniques. Data and Code: Availability Pandora is available on GitHub https://github.com/tschuelia/Pandora. All Python scripts and data to reproduce our results are available on GitHub https://github.com/tschuelia/PandoraPaper.

Authors: Julia Haag, Alexander I. Jordan, Alexandros Stamatakis

Date Published: 15th Mar 2024

Publication Type: Journal

Abstract (Expand)

Estimating the statistical robustness of the inferred tree(s) constitutes an integral part of most phylogenetic analyses. Commonly, one computes and assigns a branch support value to each inner branch of the inferred phylogeny. The most widely used method for calculating branch support on trees inferred under Maximum Likelihood (ML) is the Standard, non-parametric Felsenstein Bootstrap Support (SBS). Due to the high computational cost of the SBS, a plethora of methods has been developed to approximate it, for instance, via the Rapid Bootstrap (RB) algorithm. There have also been attempts to devise faster, alternative support measures, such as the SH-aLRT (Shimodaira–Hasegawalike approximate Likelihood Ratio Test) or the UltraFast Bootstrap 2 (UFBoot2) method. Those faster alternatives exhibit some limitations, such as the need to assess model violations (UFBoot2) or meaningless low branch support intervals (SH-aLRT). Here, we present the Educated Bootstrap Guesser (EBG), a machine learning-based tool that predicts SBS branch support values for a given input phylogeny. EBG is on average 9.4 (σ = 5.5) times faster than UFBoot2. EBG-based SBS estimates exhibit a median absolute error of 5 when predicting SBS values between 0 and 100. Furthermore, EBG also provides uncertainty measures for all per-branch SBS predictions and thereby allows for a more rigorous and careful interpretation. EBG can predict SBS support values on a phylogeny comprising 1654 SARS-CoV2 genome sequences within 3 hours on a mid-class laptop. EBG is available under GNU GPL3.

Authors: Julius Wiegert, Dimitri Höhler, Julia Haag, Alexandros Stamatakis

Date Published: 6th Mar 2024

Publication Type: Journal

Abstract (Expand)

ABSTRACT Motivation Genomes are a rich source of information on the pattern and process of evolution across biological scales. How best to make use of that information is an active area of research inat information is an active area of research in phylogenetics. Ideally, phylogenetic methods should not only model substitutions along gene trees, which explain differences between homologous gene sequences, but also the processes that generate the gene trees themselves along a shared species tree. To conduct accurate inferences, one needs to account for uncertainty at both levels, that is, in gene trees estimated from inherently short sequences and in their diverse evolutionary histories along a shared species tree. Results We present AleRax, a software that can infer reconciled gene trees together with a shared species tree using a simple, yet powerful, probabilistic model of gene duplication, transfer, and loss. A key feature of AleRax is its ability to account for uncertainty in the gene tree and its reconciliation by using an efficient approximation to calculate the joint phylogenetic-reconciliation likelihood and sample reconciled gene trees accordingly. Simulations and analyses of empirical data show that AleRax is one order of magnitude faster than competing gene tree inference tools while attaining the same accuracy. It is consistently more robust than species tree inference methods such as SpeciesRax and ASTRAL-Pro 2 under gene tree uncertainty. Finally, AleRax can process multiple gene families in parallel thereby allowing users to compare competing phylogenetic hypotheses and estimate model parameters, such as DTL probabilities for genome-scale datasets with hundreds of taxa Availability and Implementation GNU GPL at https://github.com/BenoitMorel/AleRax and data are made available at https://cme.h-its.org/exelixis/material/alerax_data.tar.gz . Contact Benoit.Morel@h-its.org Supplementary information Supplementary material is available.

Authors: Benoit Morel, Tom A. Williams, Alexandros Stamatakis, Gergely J. Szöllősi

Date Published: 7th Oct 2023

Publication Type: Journal

Abstract (Expand)

Abstract Phylogenetic inferences under the maximum likelihood criterion deploy heuristic tree search strategies to explore the vast search space. Depending on the input dataset, searches from differentt, searches from different starting trees might all converge to a single tree topology. Often, though, distinct searches infer multiple topologies with large log-likelihood score differences or yield topologically highly distinct, yet almost equally likely, trees. Recently, Haag et al. introduced an approach to quantify, and implemented machine learning methods to predict, the dataset difficulty with respect to phylogenetic inference. Easy multiple sequence alignments (MSAs) exhibit a single likelihood peak on their likelihood surface, associated with a single tree topology to which most, if not all, independent searches rapidly converge. As difficulty increases, multiple locally optimal likelihood peaks emerge, yet from highly distinct topologies. To make use of this information, we introduce and implement an adaptive tree search heuristic in RAxML-NG, which modifies the thoroughness of the tree search strategy as a function of the predicted difficulty. Our adaptive strategy is based upon three observations. First, on easy datasets, searches converge rapidly and can hence be terminated at an earlier stage. Second, overanalyzing difficult datasets is hopeless, and thus it suffices to quickly infer only one of the numerous almost equally likely topologies to reduce overall execution time. Third, more extensive searches are justified and required on datasets with intermediate difficulty. While the likelihood surface exhibits multiple locally optimal peaks in this case, a small proportion of them is significantly better. Our experimental results for the adaptive heuristic on 9,515 empirical and 5,000 simulated datasets with varying difficulty exhibit substantial speedups, especially on easy and difficult datasets (53% of total MSAs), where we observe average speedups of more than 10×. Further, approximately 94% of the inferred trees using the adaptive strategy are statistically indistinguishable from the trees inferred under the standard strategy (RAxML-NG).

Authors: Anastasis Togkousidis, Oleksiy M Kozlov, Julia Haag, Dimitri Höhler, Alexandros Stamatakis

Date Published: 1st Oct 2023

Publication Type: Journal

Abstract (Expand)

Abstract Taxonomic assignment of operational taxonomic units (OTUs) is an important bioinformatics step in analyzing environmental sequencing data. Pairwise alignment and phylogenetic‐placement methodsogenetic‐placement methods represent two alternative approaches to taxonomic assignments, but their results can differ. Here we used available colpodean ciliate OTUs from forest soils to compare the taxonomic assignments of VSEARCH (which performs pairwise alignments) and EPA‐ng (which performs phylogenetic placements). We showed that when there are differences in taxonomic assignments between pairwise alignments and phylogenetic placements at the subtaxon level, there is a low pairwise similarity of the OTUs to the reference database. We then showcase how the output of EPA‐ng can be further evaluated using GAPPA to assess the taxonomic assignments when there exist multiple equally likely placements of an OTU, by taking into account the sum over the likelihood weights of the OTU placements within a subtaxon, and the branch distances between equally likely placement locations. We also inferred the evolutionary and ecological characteristics of the colpodean OTUs using their placements within subtaxa. This study demonstrates how to fully analyze the output of EPA‐ng, by using GAPPA in conjunction with knowledge of the taxonomic diversity of the clade of interest.

Authors: Isabelle Ewers, Lubomír Rajter, Lucas Czech, Frédéric Mahé, Alexandros Stamatakis, Micah Dunthorn

Date Published: 1st Sep 2023

Publication Type: Journal

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