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      Detecting Network Communities: An Application to Phylogenetic Analysis

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          Abstract

          This paper proposes a new method to identify communities in generally weighted complex networks and apply it to phylogenetic analysis. In this case, weights correspond to the similarity indexes among protein sequences, which can be used for network construction so that the network structure can be analyzed to recover phylogenetically useful information from its properties. The analyses discussed here are mainly based on the modular character of protein similarity networks, explored through the Newman-Girvan algorithm, with the help of the neighborhood matrix . The most relevant networks are found when the network topology changes abruptly revealing distinct modules related to the sets of organisms to which the proteins belong. Sound biological information can be retrieved by the computational routines used in the network approach, without using biological assumptions other than those incorporated by BLAST. Usually, all the main bacterial phyla and, in some cases, also some bacterial classes corresponded totally (100%) or to a great extent (>70%) to the modules. We checked for internal consistency in the obtained results, and we scored close to 84% of matches for community pertinence when comparisons between the results were performed. To illustrate how to use the network-based method, we employed data for enzymes involved in the chitin metabolic pathway that are present in more than 100 organisms from an original data set containing 1,695 organisms, downloaded from GenBank on May 19, 2007. A preliminary comparison between the outcomes of the network-based method and the results of methods based on Bayesian, distance, likelihood, and parsimony criteria suggests that the former is as reliable as these commonly used methods. We conclude that the network-based method can be used as a powerful tool for retrieving modularity information from weighted networks, which is useful for phylogenetic analysis.

          Author Summary

          Complex weighted networks have been applied to uncover organizing principles of complex biological, technological, and social systems. We propose herein a new method to identify communities in such structures and apply it to phylogenetic analysis. Recent studies using this theory in genomics and proteomics contributed to the understanding of the structure and dynamics of cellular complex interaction webs. Three main distinct molecular networks have been investigated based on transcriptional and metabolic activity, and on protein interaction. Here we consider the evolutionary relationship between proteins throughout phylogeny, employing the complex network approach to perform a comparative study of the enzymes related to the chitin metabolic pathway. We show how the similarity index of protein sequences can be used for network construction, and how the underlying structure is analyzed by the computational routines of our method to recover useful and sound information for phylogenetic studies. By focusing on the modular character of protein similarity networks, we were successful in matching the identified networks modules to main bacterial phyla, and even some bacterial classes. The network-based method reported here can be used as a new powerful tool for identifying communities in complex networks, retrieving useful information for phylogenetic studies.

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          The structure and synthesis of the fungal cell wall.

          The fungal cell wall is a dynamic structure that protects the cell from changes in osmotic pressure and other environmental stresses, while allowing the fungal cell to interact with its environment. The structure and biosynthesis of a fungal cell wall is unique to the fungi, and is therefore an excellent target for the development of anti-fungal drugs. The structure of the fungal cell wall and the drugs that target its biosynthesis are reviewed. Based on studies in a number of fungi, the cell wall has been shown to be primarily composed of chitin, glucans, mannans and glycoproteins. The biosynthesis of the various components of the fungal cell wall and the importance of the components in the formation of a functional cell wall, as revealed through mutational analyses, are discussed. There is strong evidence that the chitin, glucans and glycoproteins are covalently cross-linked together and that the cross-linking is a dynamic process that occurs extracellularly. (c) 2006 Wiley Periodicals, Inc.
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            Exploring genetic interactions and networks with yeast.

            The development and application of genetic tools and resources has enabled a partial genetic-interaction network for the yeast Saccharomyces cerevisiae to be compiled. Analysis of the network, which is ongoing, has already provided a clear picture of the nature and scale of the genetic interactions that robustly sustain biological systems, and how cellular buffering is achieved at the molecular level. Recent studies in yeast have begun to define general principles of genetic networks, and also pave the way for similar studies in metazoan model systems. A comparative understanding of genetic-interaction networks promises insights into some long-standing genetic problems, such as the nature of quantitative traits and the basis of complex inherited disease.
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              Insect chitin synthases: a review.

              Chitin is the most widespread amino polysaccharide in nature. The annual global amount of chitin is believed to be only one order of magnitude less than that of cellulose. It is a linear polymer composed of N-acetylglucosamines that are joined in a reaction catalyzed by the membrane-integral enzyme chitin synthase, a member of the family 2 of glycosyltransferases. The polymerization requires UDP-N-acetylglucosamines as a substrate and divalent cations as co-factors. Chitin formation can be divided into three distinct steps. In the first step, the enzymes' catalytic domain facing the cytoplasmic site forms the polymer. The second step involves the translocation of the nascent polymer across the membrane and its release into the extracellular space. The third step completes the process as single polymers spontaneously assemble to form crystalline microfibrils. In subsequent reactions the microfibrils combine with other sugars, proteins, glycoproteins and proteoglycans to form fungal septa and cell walls as well as arthropod cuticles and peritrophic matrices, notably in crustaceans and insects. In spite of the good effort by a hardy few, our present knowledge of the structure, topology and catalytic mechanism of chitin synthases is rather limited. Gaps remain in understanding chitin synthase biosynthesis, enzyme trafficking, regulation of enzyme activity, translocation of chitin chains across cell membranes, fibrillogenesis and the interaction of microfibrils with other components of the extracellular matrix. However, cumulating genomic data on chitin synthase genes and new experimental approaches allow increasingly clearer views of chitin synthase function and its regulation, and consequently chitin biosynthesis. In the present review, I will summarize recent advances in elucidating the structure, regulation and function of insect chitin synthases as they relate to what is known about fungal chitin synthases and other glycosyltransferases.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, USA )
                1553-734X
                1553-7358
                May 2011
                May 2011
                5 May 2011
                : 7
                : 5
                : e1001131
                Affiliations
                [1 ]Institute of Physics, Federal University of Bahia, Campus Universitário de Ondina, Salvador, Bahia, Brazil
                [2 ]Institute of Mathematics, Federal University of Bahia, Campus Universitário de Ondina, Salvador, Bahia, Brazil
                [3 ]National Institute for Space Research, São José dos Campos, São Paulo, Brazil
                [4 ]Mediterranean Institute of Advanced Studies, IMEDEA (CSIC-UIB), Esporles (Islas Baleares), Spain
                [5 ]Department of Biological Sciences, State University of Feira de Santana, Feira de Santana, Bahia, Brazil
                [6 ]Institute of Biology, Federal University of Bahia, Campus Universitário de Ondina, Salvador, Bahia, Brazil
                King's College London, United Kingdom
                Author notes

                Conceived and designed the experiments: RFSA ICRN LBLS TPL AGN STRP CNEH. Performed the experiments: RFSA ICRN LBLS CNdS MVCD STRP. Analyzed the data: RFSA ICRN LBLS CNdS MVCD TPL AGN STRP CNEH. Wrote the paper: RFSA TPL AGN STRP CNEH.

                Article
                10-PLCB-RA-2861R3
                10.1371/journal.pcbi.1001131
                3088654
                21573202
                07dda859-e358-4e27-a622-8eabf1b830cb
                Andrade et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 22 September 2010
                : 4 April 2011
                Page count
                Pages: 13
                Categories
                Research Article
                Computational Biology/Evolutionary Modeling
                Computational Biology/Genomics
                Evolutionary Biology/Bioinformatics

                Quantitative & Systems biology
                Quantitative & Systems biology

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