Community Phylogenetics: Assessing Tree Reconstruction Methods and the Utility of DNA Barcodes

AbstractMaximum likelihood and maximum parsimony are two key methods for phylogenetic tree reconstruction. Under certain conditions, each of these two methods can perform more or less efficiently than the other. We show that a neural network can efficiently distinguish between four-taxon alignments that were evolved under conditions conducive to long-branch attraction, or long-branch repulsion. The feedback from the neural network can be used to select the most efficient tree reconstruction method yielding increased accuracy, when compared to a rigid choice of reconstruction methods. When applied to the contentious case of Strepsiptera evolution, our method agrees with the current scientific view.

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Scalable Models of Antibody Evolution and Benchmarking of Clonal Tree Reconstruction Methods

10.1101/2020.09.17.302505 ◽

2020 ◽

Author(s):

Chao Zhang ◽

Andrey V. Bzikadze ◽

Yana Safonova ◽

Siavash Mirarab

Keyword(s):

B Cell ◽

High Throughput Sequencing ◽

Phylogenetic Reconstruction ◽

Affinity Maturation ◽

Alternative Methods ◽

Tree Reconstruction ◽

Tree Expansion ◽

Reconstruction Methods ◽

Adequate Accuracy ◽

Better Than

AbstractAffinity maturation (AM) of antibodies through somatic hypermutations (SHMs) enables the immune system to evolve to recognize diverse pathogens. The accumulation of SHMs leads to the formation of clonal trees of antibodies produced by B cells that have evolved from a common naive B cell. Recent advances in high-throughput sequencing have enabled deep scans of antibody repertoires, paving the way for reconstructing clonal trees. However, it is not clear if clonal trees, which capture micro-evolutionary time scales, can be reconstructed using traditional phylogenetic reconstruction methods with adequate accuracy. In fact, several clonal tree reconstruction methods have been developed to fix supposed shortcomings of phylogenetic methods. Nevertheless, no consensus has been reached regarding the relative accuracy of these methods, partially because evaluation is challenging. Benchmarking the performance of existing methods and developing better methods would both benefit from realistic models of clonal tree evolution specifically designed for emulating B cell evolution. In this paper, we propose a model for modeling B cell clonal tree evolution and use this model to benchmark several existing clonal tree reconstruction methods. Our model, designed to be extensible, has several features: by evolving the clonal tree and sequences simultaneously, it allows modelling selective pressure due to changes in affinity binding; it enables scalable simulations of millions of cells; it enables several rounds of infection by an evolving pathogen; and, it models building of memory. In addition, we also suggest a set of metrics for comparing clonal trees and for measuring their properties. Our benchmarking results show that while maximum likelihood phylogenetic reconstruction methods can fail to capture key features of clonal tree expansion if applied naively, a very simple postprocessing of their results, where super short branches are contracted, leads to inferences that are better than alternative methods.

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The Shape of Modern Tree Reconstruction Methods

Systematic Biology ◽

10.1093/sysbio/syt103 ◽

2014 ◽

Vol 63 (3) ◽

pp. 436-441 ◽

Cited By ~ 8

Author(s):

Thérèse A. Holton ◽

Mark Wilkinson ◽

Davide Pisani

Keyword(s):

Tree Reconstruction ◽

Reconstruction Methods

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Hybrid tree reconstruction methods

Journal of Experimental Algorithmics ◽

10.1145/347792.347812 ◽

1999 ◽

Vol 4 ◽

pp. 5 ◽

Cited By ~ 3

Author(s):

D. Huson ◽

S. Nettles ◽

K. Rice ◽

T. Warnow ◽

S. Yooseph

Keyword(s):

Tree Reconstruction ◽

Reconstruction Methods

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Effects of taxon sampling and tree reconstruction methods on phylodiversity metrics

Ecology and Evolution ◽

10.1002/ece3.5425 ◽

2019 ◽

Vol 9 (17) ◽

pp. 9479-9499 ◽

Cited By ~ 4

Author(s):

Johanna R. Jantzen ◽

William M. Whitten ◽

Kurt M. Neubig ◽

Lucas C. Majure ◽

Douglas E. Soltis ◽

...

Keyword(s):

Taxon Sampling ◽

Tree Reconstruction ◽

Reconstruction Methods

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Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM β-Lactamases

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02930-15 ◽

2016 ◽

Vol 60 (5) ◽

pp. 2709-2717 ◽

Cited By ~ 13

Author(s):

Catharina Zeil ◽

Michael Widmann ◽

Silvia Fademrecht ◽

Constantin Vogel ◽

Jürgen Pleiss

Keyword(s):

Network Analysis ◽

Sequence Space ◽

Large Scale ◽

Current Version ◽

Tree Reconstruction ◽

Functional Protein ◽

Scale Free ◽

Reconstruction Methods ◽

Free Network ◽

Connected Sequence

ABSTRACTThe Lactamase Engineering Database (www.LacED.uni-stuttgart.de) was developed to facilitate the classification and analysis of TEM β-lactamases. The current version contains 474 TEM variants. Two hundred fifty-nine variants form a large scale-free network of highly connected point mutants. The network was divided into three subnetworks which were enriched by single phenotypes: one network with predominantly 2be and two networks with 2br phenotypes. Fifteen positions were found to be highly variable, contributing to the majority of the observed variants. Since it is expected that a considerable fraction of the theoretical sequence space is functional, the currently sequenced 474 variants represent only the tip of the iceberg of functional TEM β-lactamase variants which form a huge natural reservoir of highly interconnected variants. Almost 50% of the variants are part of a quartet. Thus, two single mutations that result in functional enzymes can be combined into a functional protein. Most of these quartets consist of the same phenotype, or the mutations are additive with respect to the phenotype. By predicting quartets from triplets, 3,916 unknown variants were constructed. Eighty-seven variants complement multiple quartets and therefore have a high probability of being functional. The construction of a TEM β-lactamase network and subsequent analyses by clustering and quartet prediction are valuable tools to gain new insights into the viable sequence space of TEM β-lactamases and to predict their phenotype. The highly connected sequence space of TEM β-lactamases is ideally suited to network analysis and demonstrates the strengths of network analysis over tree reconstruction methods.

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High-resolution scanning electron microscopy (HRSEM) of mitochondria from various rat tissues

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100102158 ◽

1988 ◽

Vol 46 ◽

pp. 14-15

Author(s):

P.J. Lea ◽

M.J. Hollenberg

Keyword(s):

Electron Microscopy ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Rat Hepatocytes ◽

Three Dimensions ◽

Objective Lens ◽

Rat Tissues ◽

Thin Sections ◽

Reconstruction Methods ◽

Scanning Electron

Our current understanding of mitochondrial ultrastructure has been derived primarily from thin sections using transmission electron microscopy (TEM). This information has been extrapolated into three dimensions by artist's impressions (1) or serial sectioning techniques in combination with computer processing (2). The resolution of serial reconstruction methods is limited by section thickness whereas artist's impressions have obvious disadvantages.In contrast, the new techniques of HRSEM used in this study (3) offer the opportunity to view simultaneously both the internal and external structure of mitochondria directly in three dimensions and in detail.The tridimensional ultrastructure of mitochondria from rat hepatocytes, retinal (retinal pigment epithelium), renal (proximal convoluted tubule) and adrenal cortex cells were studied by HRSEM. The specimens were prepared by aldehyde-osmium fixation in combination with freeze cleavage followed by partial extraction of cytosol with a weak solution of osmium tetroxide (4). The specimens were examined with a Hitachi S-570 scanning electron microscope, resolution better than 30 nm, where the secondary electron detector is located in the column directly above the specimen inserted within the objective lens.

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3-D reconstruction and analysis of mammalian mitotic spindle structure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123295 ◽

1992 ◽

Vol 50 (1) ◽

pp. 578-579

Author(s):

Kent McDonald ◽

David Mastronarde ◽

Rubai Ding ◽

Eileen O'Toole ◽

J. Richard McIntosh

Keyword(s):

Cross Sections ◽

Mitotic Spindle ◽

Experimental Studies ◽

Video Camera ◽

Three Dimensions ◽

Mitotic Spindles ◽

Black And White ◽

Reconstruction Methods ◽

Spindle Structure ◽

Tissue Culture Line

Mammalian spindles are generally large and may contain over a thousand microtubules (MTs). For this reason they are difficult to reconstruct in three dimensions and many researchers have chosen to study the smaller and simpler spindles of lower eukaryotes. Nevertheless, the mammalian spindle is used for many experimental studies and it would be useful to know its detailed structure.We have been using serial cross sections and computer reconstruction methods to analyze MT distributions in mitotic spindles of PtK cells, a mammalian tissue culture line. Images from EM negatives are digtized on a light box by a Dage MTI video camera containing a black and white Saticon tube. The signal is digitized by a Parallax 1280 graphics device in a MicroVax III computer. Microtubules are digitized at a magnification such that each is 10-12 pixels in diameter.

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Structural Studies on the Eukaryotic Ribosome

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100180033 ◽

1990 ◽

Vol 48 (1) ◽

pp. 256-257

Author(s):

Adriana Verschoor ◽

Ronald Milligan ◽

Suman Srivastava ◽

Joachim Frank

Keyword(s):

Chick Embryo ◽

3D Reconstruction ◽

Single Particle ◽

Mass Density ◽

Particle Surface ◽

Uranyl Acetate ◽

Electron Microscopic ◽

Eukaryotic Ribosome ◽

Negative Stain ◽

Reconstruction Methods

We have studied the eukaryotic ribosome from two vertebrate species (rabbit reticulocyte and chick embryo ribosomes) in several different electron microscopic preparations (Fig. 1a-d), and we have applied image processing methods to two of the types of images. Reticulocyte ribosomes were examined in both negative stain (0.5% uranyl acetate, in a double-carbon preparation) and frozen hydrated preparation as single-particle specimens. In addition, chick embryo ribosomes in tetrameric and crystalline assemblies in frozen hydrated preparation have been examined. 2D averaging, multivariate statistical analysis, and classification methods have been applied to the negatively stained single-particle micrographs and the frozen hydrated tetramer micrographs to obtain statistically well defined projection images of the ribosome (Fig. 2a,c). 3D reconstruction methods, the random conical reconstruction scheme and weighted back projection, were applied to the negative-stain data, and several closely related reconstructions were obtained. The principal 3D reconstruction (Fig. 2b), which has a resolution of 3.7 nm according to the differential phase residual criterion, can be compared to the images of individual ribosomes in a 2D tetramer average (Fig. 2c) at a similar resolution, and a good agreement of the general morphology and of many of the characteristic features is seen.Both data sets show the ribosome in roughly the same ’view’ or orientation, with respect to the adsorptive surface in the electron microscopic preparation, as judged by the agreement in both the projected form and the distribution of characteristic density features. The negative-stain reconstruction reveals details of the ribosome morphology; the 2D frozen-hydrated average provides projection information on the native mass-density distribution within the structure. The 40S subunit appears to have an elongate core of higher density, while the 60S subunit shows a more complex pattern of dense features, comprising a rather globular core, locally extending close to the particle surface.

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