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      Addressing uncertainty in genome-scale metabolic model reconstruction and analysis

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          Abstract

          The reconstruction and analysis of genome-scale metabolic models constitutes a powerful systems biology approach, with applications ranging from basic understanding of genotype-phenotype mapping to solving biomedical and environmental problems. However, the biological insight obtained from these models is limited by multiple heterogeneous sources of uncertainty, which are often difficult to quantify. Here we review the major sources of uncertainty and survey existing approaches developed for representing and addressing them. A unified formal characterization of these uncertainties through probabilistic approaches and ensemble modeling will facilitate convergence towards consistent reconstruction pipelines, improved data integration algorithms, and more accurate assessment of predictive capacity.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13059-021-02289-z.

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          Structural absorption by barbule microstructures of super black bird of paradise feathers

          Many studies have shown how pigments and internal nanostructures generate color in nature. External surface structures can also influence appearance, such as by causing multiple scattering of light (structural absorption) to produce a velvety, super black appearance. Here we show that feathers from five species of birds of paradise (Aves: Paradisaeidae) structurally absorb incident light to produce extremely low-reflectance, super black plumages. Directional reflectance of these feathers (0.05–0.31%) approaches that of man-made ultra-absorbent materials. SEM, nano-CT, and ray-tracing simulations show that super black feathers have titled arrays of highly modified barbules, which cause more multiple scattering, resulting in more structural absorption, than normal black feathers. Super black feathers have an extreme directional reflectance bias and appear darkest when viewed from the distal direction. We hypothesize that structurally absorbing, super black plumage evolved through sensory bias to enhance the perceived brilliance of adjacent color patches during courtship display.
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            antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline

            Abstract Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, β-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically.
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              A protocol for generating a high-quality genome-scale metabolic reconstruction.

              Network reconstructions are a common denominator in systems biology. Bottom-up metabolic network reconstructions have been developed over the last 10 years. These reconstructions represent structured knowledge bases that abstract pertinent information on the biochemical transformations taking place within specific target organisms. The conversion of a reconstruction into a mathematical format facilitates a myriad of computational biological studies, including evaluation of network content, hypothesis testing and generation, analysis of phenotypic characteristics and metabolic engineering. To date, genome-scale metabolic reconstructions for more than 30 organisms have been published and this number is expected to increase rapidly. However, these reconstructions differ in quality and coverage that may minimize their predictive potential and use as knowledge bases. Here we present a comprehensive protocol describing each step necessary to build a high-quality genome-scale metabolic reconstruction, as well as the common trials and tribulations. Therefore, this protocol provides a helpful manual for all stages of the reconstruction process.
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                Author and article information

                Contributors
                dsegre@bu.edu
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                18 February 2021
                18 February 2021
                2021
                : 22
                : 64
                Affiliations
                [1 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Biomedical Engineering and Biological Design Center, , Boston University, ; Boston, MA USA
                [2 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Bioinformatics Program, , Boston University, ; Boston, MA USA
                [3 ]GRID grid.5947.f, ISNI 0000 0001 1516 2393, Department of Biotechnology and Food Science, , NTNU - Norwegian University of Science and Technology, ; Trondheim, Norway
                [4 ]Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway
                [5 ]GRID grid.5947.f, ISNI 0000 0001 1516 2393, K.G. Jebsen Center for Genetic Epidemiology, , NTNU - Norwegian University of Science and Technology, ; Trondheim, Norway
                [6 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Biology and Department of Physics, , Boston University, ; Boston, MA USA
                Author information
                http://orcid.org/0000-0003-4859-1914
                Article
                2289
                10.1186/s13059-021-02289-z
                7890832
                33602294
                6a5cf48b-2500-40d7-bba8-1f514940dca1
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 22 July 2020
                : 4 February 2021
                Funding
                Funded by: US Department of Energy, Biological and Environmental Research (US)
                Award ID: DE-AC02-05CH11231
                Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: R01GM121950
                Award ID: T32GM008764
                Funded by: FundRef http://dx.doi.org/10.13039/100000072, National Institute of Dental and Craniofacial Research;
                Award ID: R01DE024468
                Funded by: FundRef http://dx.doi.org/10.13039/100000155, Division of Environmental Biology;
                Award ID: 1457695
                Funded by: FundRef http://dx.doi.org/10.13039/100000141, Division of Ocean Sciences;
                Award ID: 1635070
                Funded by: FundRef http://dx.doi.org/10.13039/100004412, Human Frontier Science Program;
                Award ID: RGP0020/2016
                Funded by: SINTEF
                Funded by: Research Council of Norway
                Award ID: 248885
                Award Recipient :
                Categories
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                © The Author(s) 2021

                Genetics
                Genetics

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