More Like this

1. Ultrafast learning of four-node hybridization cycles in phylogenetic networks using algebraic invariants

   https://doi.org/10.1093/bioadv/vbae014  

   Wu, Zhaoxing ; Solís-Lemus, Claudia ; Ouangraoua, ed., Aida ( February 2024 , Bioinformatics Advances)

   The abundance of gene flow in the Tree of Life challenges the notion that evolution can be represented with a fully bifurcating process which cannot capture important biological realities like hybridization, introgression, or horizontal gene transfer. Coalescent-based network methods are increasingly popular, yet not scalable for big data, because they need to perform a heuristic search in the space of networks as well as numerical optimization that can be NP-hard. Here, we introduce a novel method to reconstruct phylogenetic networks based on algebraic invariants. While there is a long tradition of using algebraic invariants in phylogenetics, our work is the first to define phylogenetic invariants on concordance factors (frequencies of four-taxon splits in the input gene trees) to identify level-1 phylogenetic networks under the multispecies coalescent model.

   Our novel hybrid detection methodology is optimization-free as it only requires the evaluation of polynomial equations, and as such, it bypasses the traversal of network space, yielding a computational speed at least 10 times faster than the fastest-to-date network methods. We illustrate our method’s performance on simulated and real data from the genus Canis.

   We present an open-source publicly available Julia package PhyloDiamond.jl available at https://github.com/solislemuslab/PhyloDiamond.jl with broad applicability within the evolutionary community.

    

   more » « less
2. Ensuring electronic medical record simulation through better training, modeling, and evaluation

   https://doi.org/10.1093/jamia/ocz161  

   Zhang, Ziqi ; Yan, Chao ; Mesa, Diego A. ; Sun, Jimeng ; Malin, Bradley A. ( October 2019 , Journal of the American Medical Informatics Association)

   Electronic medical records (EMRs) can support medical research and discovery, but privacy risks limit the sharing of such data on a wide scale. Various approaches have been developed to mitigate risk, including record simulation via generative adversarial networks (GANs). While showing promise in certain application domains, GANs lack a principled approach for EMR data that induces subpar simulation. In this article, we improve EMR simulation through a novel pipeline that (1) enhances the learning model, (2) incorporates evaluation criteria for data utility that informs learning, and (3) refines the training process.

   We propose a new electronic health record generator using a GAN with a Wasserstein divergence and layer normalization techniques. We designed 2 utility measures to characterize similarity in the structural properties of real and simulated EMRs in the original and latent space, respectively. We applied a filtering strategy to enhance GAN training for low-prevalence clinical concepts. We evaluated the new and existing GANs with utility and privacy measures (membership and disclosure attacks) using billing codes from over 1 million EMRs at Vanderbilt University Medical Center.

   The proposed model outperformed the state-of-the-art approaches with significant improvement in retaining the nature of real records, including prediction performance and structural properties, without sacrificing privacy. Additionally, the filtering strategy achieved higher utility when the EMR training dataset was small.

   These findings illustrate that EMR simulation through GANs can be substantially improved through more appropriate training, modeling, and evaluation criteria.

    

   more » « less
3. Topiary: Pruning the manual labor from ancestral sequence reconstruction

   https://doi.org/10.1002/pro.4551  

   Orlandi, Kona N. ; Phillips, Sophia R. ; Sailer, Zachary R. ; Harman, Joseph L. ; Harms, Michael J. ( January 2023 , Protein Science)

   Ancestral sequence reconstruction (ASR) is a powerful tool to study the evolution of proteins and thus gain deep insight into the relationships among protein sequence, structure, and function. A major barrier to its broad use is the complexity of the task: it requires multiple software packages, complex file manipulations, and expert phylogenetic knowledge. Here we introducetopiary, a software pipeline that aims to overcome this barrier. To use topiary, users prepare a spreadsheet with a handful of sequences. Topiary then: (1) Infers the taxonomic scope for the ASR study and finds relevant sequences by BLAST; (2) Does taxonomically informed sequence quality control and redundancy reduction; (3) Constructs a multiple sequence alignment; (4) Generates a maximum‐likelihood gene tree; (5) Reconciles the gene tree to the species tree; (6) Reconstructs ancestral amino acid sequences; and (7) Determines branch supports. The pipeline returns annotated evolutionary trees, spreadsheets with sequences, and graphical summaries of ancestor quality. This is achieved by integrating modern phylogenetics software (Muscle5, RAxML‐NG, GeneRax, and PastML) with online databases (NCBI and the Open Tree of Life). In this paper, we introduce non‐expert readers to the steps required for ASR, describe the specific design choices made intopiary, provide a detailed protocol for users, and then validate the pipeline using datasets from a broad collection of protein families. Topiary is freely available for download:https://github.com/harmslab/topiary.

    

   more » « less
4. Fast Bayesian Inference of Phylogenies from Multiple Continuous Characters

   https://doi.org/10.1093/sysbio/syad067  

   Zhang, Rong ; Drummond, Alexei J. ; Mendes, Fábio K. ; Matschiner, ed., Michael ( December 2023 , Systematic Biology)

   Time-scaled phylogenetic trees are an ultimate goal of evolutionary biology and a necessary ingredient in comparative studies. The accumulation of genomic data has resolved the tree of life to a great extent, yet timing evolutionary events remain challenging if not impossible without external information such as fossil ages and morphological characters. Methods for incorporating morphology in tree estimation have lagged behind their molecular counterparts, especially in the case of continuous characters. Despite recent advances, such tools are still direly needed as we approach the limits of what molecules can teach us. Here, we implement a suite of state-of-the-art methods for leveraging continuous morphology in phylogenetics, and by conducting extensive simulation studies we thoroughly validate and explore our methods’ properties. While retaining model generality and scalability, we make it possible to estimate absolute and relative divergence times from multiple continuous characters while accounting for uncertainty. We compile and analyze one of the most data-type diverse data sets to date, comprised of contemporaneous and ancient molecular sequences, and discrete and continuous morphological characters from living and extinct Carnivora taxa. We conclude by synthesizing lessons about our method’s behavior, and suggest future research venues.

    

   more » « less
5. Phylogeny and multiple independent whole‐genome duplication events in the Brassicales

   https://doi.org/10.1002/ajb2.1514  

   Mabry, Makenzie E. ; Brose, Julia M. ; Blischak, Paul D. ; Sutherland, Brittany ; Dismukes, Wade T. ; Bottoms, Christopher A. ; Edger, Patrick P. ; Washburn, Jacob D. ; An, Hong ; Hall, Jocelyn C. ; et al ( August 2020 , American Journal of Botany)

   Whole‐genome duplications (WGDs) are prevalent throughout the evolutionary history of plants. For example, dozens of WGDs have been phylogenetically localized across the order Brassicales, specifically, within the family Brassicaceae. A WGD event has also been identified in the Cleomaceae, the sister family to Brassicaceae, yet its placement, as well as that of WGDs in other families in the order, remains unclear.

   Phylo‐transcriptomic data were generated and used to infer a nuclear phylogeny for 74 Brassicales taxa. Genome survey sequencing was also performed on 66 of those taxa to infer a chloroplast phylogeny. These phylogenies were used to assess and confirm relationships among the major families of the Brassicales and within Brassicaceae. Multiple WGD inference methods were then used to assess the placement of WGDs on the nuclear phylogeny.

   Well‐supported chloroplast and nuclear phylogenies for the Brassicales and the putative placement of the Cleomaceae‐specific WGD event Th‐ɑ are presented. This work also provides evidence for previously hypothesized WGDs, including a well‐supported event shared by at least two members of the Resedaceae family, and a possible event within the Capparaceae.

   Phylogenetics and the placement of WGDs within highly polyploid lineages continues to be a major challenge. This study adds to the conversation on WGD inference difficulties by demonstrating that sampling is especially important for WGD identification and phylogenetic placement. Given its economic importance and genomic resources, the Brassicales continues to be an ideal group for assessing WGD inference methods.

    

   more » « less