MOTIVATION: Sequence simulations along phylogenetic trees play an important role in numerous molecular evolution studies such as benchmarking algorithms for ancestral sequence reconstruction, multiple sequence alignment, and phylogeny inference. They are also used in phylogenetic model-selection tasks, including the inference of selective forces. Recently, Approximate Bayesian Computation (ABC)-based approaches have been developed for inferring parameters of complex evolutionary models, which rely on massive generation of simulated data. For all these applications, computationally efficient sequence simulators are essential. RESULTS: In this study, we investigate fast algorithms for simulating sequences along a phylogenetic tree, focusing on accelerating the speed-limiting component of the simulation process: handling insertion and deletion (indel) events. We demonstrate that data structures which efficiently store indel events along a tree can substantially accelerate the simulation process compared to a naive approach. To illustrate the utility of this efficient simulator, we integrated it into an ABC-based algorithm for inferring indel model parameters and applied it to study indel dynamics within Chiroptera. AVAILABILITY AND IMPLEMENTATION: The source code for the different simulation algorithms, alongside the data used, is available at: https://github.com/nimrodSerokTAU/evo-sim. The simulator has also been integrated into SpartaABC, a website for the inference of indel parameters, accessible at: https://spartaabc.tau.ac.il/.

MOTIVATION: Multiple sequence alignments (MSAs) are extensively used in biology, from phylogenetic reconstruction to structure and function prediction. Here, we suggest an out-of-the-box approach for the inference of MSAs, which relies on algorithms developed for processing natural languages. We show that our artificial intelligence (AI)-based methodology can be trained to align sequences by processing alignments that are generated via simulations, and thus different aligners can be easily generated for datasets with specific evolutionary dynamics attributes. We expect that natural language processing (NLP) solutions will replace or augment classic solutions for computing alignments, and more generally, challenging inference tasks in phylogenomics. RESULTS: The MSA problem is a fundamental pillar in bioinformatics, comparative genomics, and phylogenetics. Here, we characterize and improve BetaAlign, the first deep learning aligner, which substantially deviates from conventional algorithms of alignment computation. BetaAlign draws on NLP techniques and trains transformers to map a set of unaligned biological sequences to an MSA. We show that our approach is highly accurate, comparable and sometimes better than state-of-the-art alignment tools. We characterize the performance of BetaAlign and the effect of various aspects on accuracy; for example, the size of the training data, the effect of different transformer architectures, and the effect of learning on a subspace of indel-model parameters (subspace learning). We also introduce a new technique that leads to improved performance compared to our previous approach. Our findings further uncover the potential of NLP-based methods for sequence alignment, highlighting that AI-based algorithms can substantially challenge classic approaches in phylogenomics and bioinformatics. AVAILABILITY AND IMPLEMENTATION: Datasets used in this work are available on HuggingFace (Wolf et al. Transformers: state-of-the-art natural language processing. In: Proceedings of the 2020 Conference on Empirical Methods in Natural Language Processing: System Demonstrations. p.38-45. 2020) at: https://huggingface.co/dotan1111. Source code is available at: https://github.com/idotan286/SimulateAlignments.

MOTIVATION: Currently used methods for estimating branch support in phylogenetic analyses often rely on the classic Felsenstein's bootstrap, parametric tests, or their approximations. As these branch support scores are widely used in phylogenetic analyses, having accurate, fast, and interpretable scores is of high importance. RESULTS: Here, we employed a data-driven approach to estimate branch support values with a probabilistic interpretation. To this end, we simulated thousands of realistic phylogenetic trees and the corresponding multiple sequence alignments. Each of the obtained alignments was used to infer the phylogeny using state-of-the-art phylogenetic inference software, which was then compared to the true tree. Using these extensive data, we trained machine-learning algorithms to estimate branch support values for each bipartition within the maximum-likelihood trees obtained by each software. Our results demonstrate that our model provides fast and more accurate probability-based branch support values than commonly used procedures. We demonstrate the applicability of our approach on empirical datasets. AVAILABILITY AND IMPLEMENTATION: The data supporting this work are available in the Figshare repository at https://doi.org/10.6084/m9.figshare.25050554.v1, and the underlying code is accessible via GitHub at https://github.com/noaeker/bootstrap_repo.

MOTIVATION: In recent years, full-genome sequences have become increasingly available and as a result many modern phylogenetic analyses are based on very long sequences, often with over 100 000 sites. Phylogenetic reconstructions of large-scale alignments are challenging for likelihood-based phylogenetic inference programs and usually require using a powerful computer cluster. Current tools for alignment trimming prior to phylogenetic analysis do not promise a significant reduction in the alignment size and are claimed to have a negative effect on the accuracy of the obtained tree. RESULTS: Here, we propose an artificial-intelligence-based approach, which provides means to select the optimal subset of sites and a formula by which one can compute the log-likelihood of the entire data based on this subset. Our approach is based on training a regularized Lasso-regression model that optimizes the log-likelihood prediction accuracy while putting a constraint on the number of sites used for the approximation. We show that computing the likelihood based on 5% of the sites already provides accurate approximation of the tree likelihood based on the entire data. Furthermore, we show that using this Lasso-based approximation during a tree search decreased running-time substantially while retaining the same tree-search performance. AVAILABILITY AND IMPLEMENTATION: The code was implemented in Python version 3.8 and is available through GitHub (https://github.com/noaeker/lasso_positions_sampling). The datasets used in this paper were retrieved from Zhou et al. (2018) as described in section 3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.