Nonbifurcating Phylogenetic Tree Inference via the Adaptive LASSO.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang C
PROVIDER: S-EPMC8300927 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bayesian inference of phylogeny with MCMC plays a key role in the study of evolution. Yet, this method still suffers from a practical challenge identified more than two decades ago: designing tree topology proposals that efficiently sample tree spaces. In this article, I introduce the concept of adaptive tree proposals for unrooted topologies, that is tree proposals adapting to the posterior distribution as it is estimated. I use this concept to elaborate two adaptive variants of existing proposals and an adaptive proposal based on a novel design philosophy in which the structure of the proposal is informed by the posterior distribution of trees. I investigate the performance of these proposals by first presenting a metric that captures the performance of each proposal within a mixture of proposals. Using this metric, I compare the performance of the adaptive proposals to the performance of standard and parsimony-guided proposals on 11 empirical datasets. Using adaptive proposals led to consistent performance gains and resulted in up to 18-fold increases in mixing efficiency and 6-fold increases in convergence rate without increasing the computational cost of these analyses.
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Project description:Methodological advancements, including propensity score methods, have resulted in improved unbiased estimation of treatment effects from observational data. Traditionally, a "throw in the kitchen sink" approach has been used to select covariates for inclusion into the propensity score, but recent work shows including unnecessary covariates can impact both the bias and statistical efficiency of propensity score estimators. In particular, the inclusion of covariates that impact exposure but not the outcome, can inflate standard errors without improving bias, while the inclusion of covariates associated with the outcome but unrelated to exposure can improve precision. We propose the outcome-adaptive lasso for selecting appropriate covariates for inclusion in propensity score models to account for confounding bias and maintaining statistical efficiency. This proposed approach can perform variable selection in the presence of a large number of spurious covariates, that is, covariates unrelated to outcome or exposure. We present theoretical and simulation results indicating that the outcome-adaptive lasso selects the propensity score model that includes all true confounders and predictors of outcome, while excluding other covariates. We illustrate covariate selection using the outcome-adaptive lasso, including comparison to alternative approaches, using simulated data and in a survey of patients using opioid therapy to manage chronic pain.
| S-EPMC5591052 | biostudies-literature
Project description:Effect modification occurs when the effect of the treatment on an outcome varies according to the level of other covariates and often has important implications in decision-making. When there are tens or hundreds of covariates, it becomes necessary to use the observed data to select a simpler model for effect modification and then make valid statistical inference. We propose a two-stage procedure to solve this problem. First, we use Robinson's transformation to decouple the nuisance parameters from the treatment effect of interest and use machine learning algorithms to estimate the nuisance parameters. Next, after plugging in the estimates of the nuisance parameters, we use the lasso to choose a low-complexity model for effect modification. Compared to a full model consisting of all the covariates, the selected model is much more interpretable. Compared to the univariate subgroup analyses, the selected model greatly reduces the number of false discoveries. We show that the conditional selective inference for the selected model is asymptotically valid given the rate assumptions in classical semiparametric regression. Extensive simulation studies are conducted to verify the asymptotic results and an epidemiological application is used to demonstrate the method.
| S-EPMC9491375 | biostudies-literature
Project description:MotivationIn 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.ResultsHere, 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 implementationThe 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 informationSupplementary data are available at Bioinformatics online.
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Project description:Reconstructing the evolution of tumors is a key aspect towards the identification of appropriate cancer therapies. The task is challenging because tumors evolve as heterogeneous cell populations. Single-cell sequencing holds the promise of resolving the heterogeneity of tumors; however, it has its own challenges including elevated error rates, allelic drop-out, and uneven coverage. Here, we develop a new approach to mutation detection in individual tumor cells by leveraging the evolutionary relationship among cells. Our method, called SCI?, jointly calls mutations in individual cells and estimates the tumor phylogeny among these cells. Employing a Markov Chain Monte Carlo scheme enables us to reliably call mutations in each single cell even in experiments with high drop-out rates and missing data. We show that SCI? outperforms existing methods on simulated data and applied it to different real-world datasets, namely a whole exome breast cancer as well as a panel acute lymphoblastic leukemia dataset.
| S-EPMC6279798 | biostudies-other
Project description:Graphical models are a popular approach to find dependence and conditional independence relationships between gene expressions. Directed acyclic graphs (DAGs) are a special class of directed graphical models, where all the edges are directed edges and contain no directed cycles. The DAGs are well known models for discovering causal relationships between genes in gene regulatory networks. However, estimating DAGs without assuming known ordering is challenging due to high dimensionality, the acyclic constraints, and the presence of equivalence class from observational data. To overcome these challenges, we propose a two-stage adaptive Lasso approach, called NS-DIST, which performs neighborhood selection (NS) in stage 1, and then estimates DAGs by the Discrete Improving Search with Tabu (DIST) algorithm within the selected neighborhood. Simulation studies are presented to demonstrate the effectiveness of the method and its computational efficiency. Two real data examples are used to demonstrate the practical usage of our method for gene regulatory network inference.
| S-EPMC5322863 | biostudies-literature
Project description:BackgroundThe nonparametric bootstrap is widely used to measure the branch support of phylogenetic trees. However, bootstrapping is computationally expensive and remains a bottleneck in phylogenetic analyses. Recently, an ultrafast bootstrap approximation (UFBoot) approach was proposed for maximum likelihood analyses. However, such an approach is still missing for maximum parsimony.ResultsTo close this gap we present MPBoot, an adaptation and extension of UFBoot to compute branch supports under the maximum parsimony principle. MPBoot works for both uniform and non-uniform cost matrices. Our analyses on biological DNA and protein showed that under uniform cost matrices, MPBoot runs on average 4.7 (DNA) to 7 times (protein data) (range: 1.2-20.7) faster than the standard parsimony bootstrap implemented in PAUP*; but 1.6 (DNA) to 4.1 times (protein data) slower than the standard bootstrap with a fast search routine in TNT (fast-TNT). However, for non-uniform cost matrices MPBoot is 5 (DNA) to 13 times (protein data) (range:0.3-63.9) faster than fast-TNT. We note that MPBoot achieves better scores more frequently than PAUP* and fast-TNT. However, this effect is less pronounced if an intensive but slower search in TNT is invoked. Moreover, experiments on large-scale simulated data show that while both PAUP* and TNT bootstrap estimates are too conservative, MPBoot bootstrap estimates appear more unbiased.ConclusionsMPBoot provides an efficient alternative to the standard maximum parsimony bootstrap procedure. It shows favorable performance in terms of run time, the capability of finding a maximum parsimony tree, and high bootstrap accuracy on simulated as well as empirical data sets. MPBoot is easy-to-use, open-source and available at http://www.cibiv.at/software/mpboot .
| S-EPMC5796505 | biostudies-literature
Project description:MotivationDifferential network inference is a fundamental and challenging problem to reveal gene interactions and regulation relationships under different conditions. Many algorithms have been developed for this problem; however, they do not consider the differences between the importance of genes, which may not fit the real-world situation. Different genes have different mutation probabilities, and the vital genes associated with basic life activities have less fault tolerance to mutation. Equally treating all genes may bias the results of differential network inference. Thus, it is necessary to consider the importance of genes in the models of differential network inference.ResultsBased on the Gaussian graphical model with adaptive gene importance regularization, we develop a novel importance-penalized joint graphical Lasso method, IPJGL, for differential network inference. The presented method is validated by the simulation experiments as well as the real datasets. Furthermore, to precisely evaluate the results of differential network inference, we propose a new metric named APC2 for the differential levels of gene pairs. We apply IPJGL to analyze the TCGA colorectal and breast cancer datasets and find some candidate cancer genes with significant survival analysis results, including SOST for colorectal cancer and RBBP8 for breast cancer. We also conduct further analysis based on the interactions in the Reactome database and confirm the utility of our method.AvailabilityR source code of importance-penalized joint graphical lasso is freely available at https://github.com/Wu-Lab/IPJGL.Supplementary informationSupplementary materials are available at Bioinformatics online.
| S-EPMC8756181 | biostudies-literature
Project description:Recently, an increasing number of studies sequence multiple biopsies of primary tumors, and even paired metastatic tumors to understand heterogeneity and the evolutionary trajectory of cancer progression. Although several algorithms are available to infer the phylogeny, most tools rely on accurate measurements of mutation allele frequencies from deep sequencing, which is often hard to achieve for clinical samples (especially FFPE samples). In this study, we present a novel and easy-to-use method, PTI (Phylogenetic Tree Inference), which use an iterative top-down approach to infer the phylogenetic tree structure of multiple tumor biopsies from same patient using just the presence or absence of somatic mutations without their allele frequencies. Therefore PTI can be used in a wide range of cases even when allele frequency data is not available. Comparison with existing state-of-the-art methods, such as LICHeE, Treeomics, and BAMSE, shows that PTI achieves similar or slightly better performance within a short run time. Moreover, this method is generally applicable to infer phylogeny for any other data sets (such as epigenetics) with a similar zero and one feature-by-sample matrix.
| S-EPMC7020887 | biostudies-literature
Project description:Sampling across tree space is one of the major challenges in Bayesian phylogenetic inference using Markov chain Monte Carlo (MCMC) algorithms. Standard MCMC tree moves consider small random perturbations of the topology, and select from candidate trees at random or based on the distance between the old and new topologies. MCMC algorithms using such moves tend to get trapped in tree space, making them slow in finding the globally most probable trees (known as "convergence") and in estimating the correct proportions of the different types of them (known as "mixing"). Here, we introduce a new class of moves, which propose trees based on their parsimony scores. The proposal distribution derived from the parsimony scores is a quickly computable albeit rough approximation of the conditional posterior distribution over candidate trees. We demonstrate with simulations that parsimony-guided moves correctly sample the uniform distribution of topologies from the prior. We then evaluate their performance against standard moves using six challenging empirical data sets, for which we were able to obtain accurate reference estimates of the posterior using long MCMC runs, a mix of topology proposals, and Metropolis coupling. On these data sets, ranging in size from 357 to 934 taxa and from 1740 to 5681 sites, we find that single chains using parsimony-guided moves usually converge an order of magnitude faster than chains using standard moves. They also exhibit better mixing, that is, they cover the most probable trees more quickly. Our results show that tree moves based on quick and dirty estimates of the posterior probability can significantly outperform standard moves. Future research will have to show to what extent the performance of such moves can be improved further by finding better ways of approximating the posterior probability, taking the trade-off between accuracy and speed into account. [Bayesian phylogenetic inference; MCMC; parsimony; tree proposal.].
| S-EPMC7440752 | biostudies-literature