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      eNanoMapper: harnessing ontologies to enable data integration for nanomaterial risk assessment

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          Abstract

          Engineered nanomaterials (ENMs) are being developed to meet specific application needs in diverse domains across the engineering and biomedical sciences (e.g. drug delivery). However, accompanying the exciting proliferation of novel nanomaterials is a challenging race to understand and predict their possibly detrimental effects on human health and the environment. The eNanoMapper project (www.enanomapper.net) is creating a pan-European computational infrastructure for toxicological data management for ENMs, based on semantic web standards and ontologies. Here, we describe the development of the eNanoMapper ontology based on adopting and extending existing ontologies of relevance for the nanosafety domain. The resulting eNanoMapper ontology is available at http://purl.enanomapper.net/onto/enanomapper.owl. We aim to make the re-use of external ontology content seamless and thus we have developed a library to automate the extraction of subsets of ontology content and the assembly of the subsets into an integrated whole. The library is available (open source) at http://github.com/enanomapper/slimmer/. Finally, we give a comprehensive survey of the domain content and identify gap areas. ENM safety is at the boundary between engineering and the life sciences, and at the boundary between molecular granularity and bulk granularity. This creates challenges for the definition of key entities in the domain, which we also discuss.

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          Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

          It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.
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            Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment.

            Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein-nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references).
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              Uberon, an integrative multi-species anatomy ontology

              We present Uberon, an integrated cross-species ontology consisting of over 6,500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://uberon.org
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                Author and article information

                Contributors
                hastings@ebi.ac.uk
                jeliazkova.nina@gmail.com
                gowen@ebi.ac.uk
                g_tsiliki@hotmail.com
                muntisa@gmail.com
                steinbeck@ebi.ac.uk
                egon.willighagen@gmail.com
                Journal
                J Biomed Semantics
                J Biomed Semantics
                Journal of Biomedical Semantics
                BioMed Central (London )
                2041-1480
                21 March 2015
                21 March 2015
                2015
                : 6
                : 10
                Affiliations
                [ ]European Molecular Biology Laboratory – European Bioinformatics Institute (EMBL-EBI), Cambridge, United Kingdom
                [ ]IdeaConsult Ltd., 4.A.Kanchev str., Sofia, Bulgaria
                [ ]National Technical University of Athens (NTUA), Athens, Greece
                [ ]Computer Science Faculty, University of A Coruña, A Coruña, Spain
                [ ]Department of Bioinformatics – BiGCaT, NUTRIM, Maastricht University, Maastricht, Netherlands
                Article
                5
                10.1186/s13326-015-0005-5
                4374589
                25815161
                7f55b63d-96f2-4a3b-839f-0731cf2ac76e
                © Hastings et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.

                History
                : 3 November 2014
                : 27 February 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Bioinformatics & Computational biology
                nanomaterial,safety,ontology
                Bioinformatics & Computational biology
                nanomaterial, safety, ontology

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