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      ShadowCaster: Compositional Methods under the Shadow of Phylogenetic Models to Detect Horizontal Gene Transfers in Prokaryotes

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          Abstract

          Horizontal gene transfer (HGT) plays an important role for evolutionary innovations within prokaryotic communities and is a crucial event for their survival. Several computational approaches have arisen to identify HGT events in recipient genomes. However, this has been proven to be a complex task due to the generation of a great number of false positives and the prediction disagreement among the existing methods. Phylogenetic reconstruction methods turned out to be the most reliable ones, but they are not extensible to all genes/species and are computationally demanding when dealing with large datasets. In contrast, the so-called surrogate methods that use heuristic solutions either based on nucleotide composition patterns or phyletic distribution of BLAST hits can be applied easily to the genomic scale, but they fail in identifying common HGT events. Here, we present ShadowCaster, a hybrid approach that sequentially combines nucleotide composition-based predictions by support vector machines (SVMs) under the shadow of phylogenetic models independent of tree reconstruction, to improve the detection of HGT events in prokaryotes. ShadowCaster successfully predicted close and distant HGT events in both artificial and bacterial genomes. ShadowCaster detected HGT related to heavy metal resistance in the genome of Rhodanobacter denitrificans with higher accuracy than the most popular state-of-the-art computational approaches, encompassing most of the predicted cases made by other methods. ShadowCaster is released at the GitHub platform as an open-source software under the GPLv3 license.

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          Most cited references22

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          Functional and evolutionary implications of gene orthology.

          Orthologues and paralogues are types of homologous genes that are related by speciation or duplication, respectively. Orthologous genes are generally assumed to retain equivalent functions in different organisms and to share other key properties. Several recent comparative genomic studies have focused on testing these expectations. Here we discuss the complexity of the evolution of gene-phenotype relationships and assess the validity of the key implications of orthology and paralogy relationships as general statistical trends and guiding principles.
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            Adaptive evolution of bacterial metabolic networks by horizontal gene transfer.

            Numerous studies have considered the emergence of metabolic pathways, but the modes of recent evolution of metabolic networks are poorly understood. Here, we integrate comparative genomics with flux balance analysis to examine (i) the contribution of different genetic mechanisms to network growth in bacteria, (ii) the selective forces driving network evolution and (iii) the integration of new nodes into the network. Most changes to the metabolic network of Escherichia coli in the past 100 million years are due to horizontal gene transfer, with little contribution from gene duplicates. Networks grow by acquiring genes involved in the transport and catalysis of external nutrients, driven by adaptations to changing environments. Accordingly, horizontally transferred genes are integrated at the periphery of the network, whereas central parts remain evolutionarily stable. Genes encoding physiologically coupled reactions are often transferred together, frequently in operons. Thus, bacterial metabolic networks evolve by direct uptake of peripheral reactions in response to changed environments.
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              Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands.

              There is a growing literature on the detection of Horizontal Gene Transfer (HGT) events by means of parametric, non-comparative methods. Such approaches rely only on sequence information and utilize different low and high order indices to capture compositional deviation from the genome backbone; the superiority of the latter over the former has been shown elsewhere. However even high order k-mers may be poor estimators of HGT, when insufficient information is available, e.g. in short sliding windows. Most of the current HGT prediction methods require pre-existing annotation, which may restrict their application on newly sequenced genomes. We introduce a novel computational method, Interpolated Variable Order Motifs (IVOMs), which exploits compositional biases using variable order motif distributions and captures more reliably the local composition of a sequence compared with fixed-order methods. For optimal localization of the boundaries of each predicted region, a second order, two-state hidden Markov model (HMM) is implemented in a change-point detection framework. We applied the IVOM approach to the genome of Salmonella enterica serovar Typhi CT18, a well-studied prokaryote in terms of HGT events, and we show that the IVOMs outperform state-of-the-art low and high order motif methods predicting not only the already characterized Salmonella Pathogenicity Islands (SPI-1 to SPI-10) but also three novel SPIs (SPI-15, SPI-16, SPI-17) and other HGT events. The software is available under a GPL license as a standalone application at http://www.sanger.ac.uk/Software/analysis/alien_hunter gsv@sanger.ac.uk Supplementary data are available at Bioinformatics online.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                07 July 2020
                July 2020
                : 11
                : 7
                : 756
                Affiliations
                [1 ]Departamento de Ciencias Biológicas, Universidad Técnica Particular de Loja, Loja 110108, Ecuador; nela.sanchez96@ 123456gmail.com
                [2 ]CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Porto, Portugal; gchapin@ 123456ciimar.up.pt (G.A.-C.); aantunes@ 123456ciimar.up.pt (A.A.)
                [3 ]Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
                [4 ]Grupo de Bio-Quimioinformática & Carrera de Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Agropecuarias, Universidad de Las Américas, Quito EC170125, Ecuador; vinicio.armijos@ 123456udla.edu.ec (V.A.-J.); eduardo.tejera@ 123456udla.edu.ec (E.T.)
                [5 ]Grupo de Bio-Quimioinformática & Escuela de Ciencias Físicas y Matemáticas, Universidad de Las Américas, Quito EC170125, Ecuador; yunierkis.perez@ 123456udla.edu.ec
                Author notes
                [* ]Correspondence: asanchez2@ 123456utpl.edu.ec ; Tel.: +593-07-370-1444
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-9908-2418
                https://orcid.org/0000-0003-2965-2515
                https://orcid.org/0000-0002-3710-0035
                https://orcid.org/0000-0002-1328-1732
                Article
                genes-11-00756
                10.3390/genes11070756
                7397055
                32645885
                c7f99a1b-ddb7-49f0-b095-63bf7dbf93f9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 June 2020
                : 30 June 2020
                Categories
                Article

                horizontal gene transfer,parametric method,implicit phylogenetic model,hybrid approach

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