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MIRAGE: The minimum information required for a glycomics experiment

MIRAGE: The minimum information required for a glycomics experiment Glycobiology vol. 24 no. 5 pp. 402–406, 2014 doi:10.1093/glycob/cwu018 Advance Access publication on March 20, 2014 MIRAGE: The minimum information required for a glycomics experiment 2 3 William S York , Sanjay Agravat , Kiyoko FAoki- diverse methods, including mass spectrometry (MS), 4 5,6 7 Kinoshita , Ryan McBride , Matthew P Campbell , chromatography, glycan array-binding assays, nuclear mag- 8 9 10 Catherine E Costello , Anne Dell , Ten Feizi , Stuart netic resonance (NMR) and other rapidly developing tech- 9 11 12 M Haslam , Niclas Karlsson , Kay-Hooi Khoo , nologies. The acceptance of these guidelines by scientists 13 10 14 Daniel Kolarich , Yan Liu , Milos Novotny , Nicolle conducting research on biological systems in which glycans 7 5,6 15 HPacker , James C Paulson , Erdmann Rapp , have a significant role will facilitate the evaluation and repro- 2 16 17 Rene Ranzinger , Pauline M Rudd , David F Smith , duction of glycomics experiments and data that is reported 18 2 2 Weston B Struwe , Michael Tiemeyer , Lance Wells , in scientific journals and uploaded to glycomics databases. 7 1,19 Joseph Zaia , and Carsten Kettner As a first step, MIRAGE guidelines for glycan analysis by 2 MS have been recently published (Kolarich D, Rapp E, Complex Carbohydrate Research Center, University of Georgia, 315 Struwe WB, Haslam SM, Zaia J., et al. 2013. The minimum Riverbend Road, Athens, GA 30602, USA; Center for Comprehensive Informatics, Emory University, 1784 N. Decatur Rd, Atlanta, GA 30322, USA; information required for a glycomics experiment (MIRAGE) Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 project – Improving the standards for reporting mass Tangi-machi, Hachioji, Tokyo 192-8577, Japan; Department of Cell and spectrometry-based glycoanalytic data. Mol. Cell Proteomics. Molecular Biology; Department of Physiological Chemistry, The Scripps 12:991–995), allowing them to be implemented and evaluated Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA; in the context of real-world glycobiology research. In this Biomolecular Frontiers Research Centre, Macquarie University, Sydney, NSW 2109, Australia; Center for Biomedical Mass Spectrometry, Department of paper, we set out the historical context, organization structure Biochemistry, Boston University, School of Medicine, 670 Albany Street, Suite and overarching objectives of the MIRAGE initiative. 504, Boston, MA 02118, USA; Department of Life Sciences, Imperial College London, London SW7 2AZ, UK; Glycosciences Laboratory Department of Medicine, Imperial College London, London W12 0NN, UK; Medical Biochemistry, University of Gothenburg, PO Box 440, 405 30 Gothenburg, Sweden; Institute of Biological Chemistry, Academia Sinica, 128, Academia Background Road Sec. 2, Nankang, Taipei 115, Taiwan; Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Advances in our ability to identify and quantify complex glycans Germany; Department of Chemistry, Indiana University, 800 E. Kirkwood 15 and glycoconjugates has led to an increasing awareness of the key Avenue, Bloomington, IN 47405, USA; Bioprocess Engineering, Max Planck roles that these molecules play in a wide range of physiological Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany; NIBRT GlycoScience Group, NIBRT – National Institute for and pathological processes, including cell adherence, cell–cell Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, interactions, molecular trafficking, biosynthetic quality control, Blackrock, Co. Dublin, Ireland; Department of Biochemistry, School of signal transduction and host–pathogen recognition. Various types Medicine, Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA; of glycans and glycoconjugates are thus becoming recognized as Department of Chemistry, Chemistry Research Laboratory, University of essential participants in almost all biological processes. Structural Oxford, Oxford OX1 3TA, UK; and Beilstein-Institut, Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany analysis of glycoconjugates is technically challenging, requiring sophisticated analytical and computational techniques applied at The MIRAGE (minimum information required for a glyco- the interface of biology and chemistry. Although recent technical mics experiment) initiative was founded in Seattle, WA, in advances in this area have led to the emergence of glycomics as a November 2011 in order to develop guidelines for reporting distinct discipline, progress is slowed by the unavailability of the qualitative and quantitative results obtained by diverse robust, generally applicable software tools required to process, an- types of glycomics analyses, including the conditions and tech- notate, archive and mine the data now being generated in this niques that were applied to prepare the glycans for analysis domain. and generate the primary data along with the tools and para- The complexity of glycans and the diversity of their structures meters that were used to process and annotate this data. and molecular contexts have necessitated the development of a These guidelines must address a broad range of issues, as gly- wide range of experimental techniques and instrumentation for comics data are inherently complex and are generated using their analysis. Although mass spectrometry (MS) is the most fre- quently applied methodology for glycan analysis, array-based ligand-binding assays, high-performance liquid chromatography, capillary electrophoresis (CE), nuclear magnetic resonance To whom correspondence should be addressed: Tel: +49-(0)69-7167-3221; Fax: +49-(0)69-7167-3219; e-mail: ckettner@beilstein-institut.de (NMR) and several other techniques are now being routinely © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by- nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 402 Minimum information required for a glycomics experiment used for this purpose. Recent advances in analytical method- detailed than the Athens Guidelines. However, the two sets of ology and instrumentation make it possible to produce glycomics guidelines are mutually consistent and complementary. data with increased depth, speed and efficiency, resulting in the The MIRAGE guidelines provide reviewers with specific, generation of extremely large and diverse datasets. However, the technical descriptions of the metadata required to evaluate the reporting and/or distribution of information obtained during a glycomics analysis, and can thus be used by a qualified review- glycomics experiment pose unique challenges to the analyst. er as a basis for making judgments regarding the validity of This includes the identification and presentation of relevant specific conclusions in the manuscript. However, they are not metadata that allows the results to be objectively evaluated and intended to substitute for the review process itself or to define interpreted in a biological context and reproduced in the labora- acceptance criteria for submitted manuscripts. tories of other scientists. The criteria for acceptance of glycomics data for inclusion It is important to note that glycomics cannot be viewed as a into a database are likely to be somewhat different than those straightforward extension of proteomics. Glycomics and pro- for acceptance in a scientific journal. For example, the curator- teomics experiments share the same basic goal, i.e. the identifi- ial process for inclusion of a dataset in a database may not cation and quantification (where possible) of specific molecular include review by an expert. In such cases, rigorous guidelines structures in a particular biological context. However, the com- for the inclusion of metadata are crucial, as these metadata are a plex and often branched structures of glycans, in combination necessary prerequisite for the (automated or manual) selection with the non-template-driven mechanisms leading to their bio- of relevant, trusted data from the database for comparison to synthesis, have made the emergence of glycomics as a discip- new datasets or inclusion in data-mining investigations. We line dependent on the ongoing development of new analytical expect that the MIRAGE guidelines (developed by analysts, approaches and computational tools that are not required for pro- biologists and bioinformaticians with glycomics expertise) will teomics. The quality and information content of the annotated serve as a convenient foundation to define the information that data generated by such tools can vary considerably, depending has to be stored in a database to provide comprehensive and re- on the exact experimental conditions used to generate primary producible datasets to its users. data, the suitability and configuration of the computational tools used to process this data, the quality of any databases that are invoked during the data processing and the validity of any MIRAGE assumptions that are made when assigning glycan structures in the presence of incomplete analytical data. In 2006, participants at the Workshop on Analytical and The validity of glycan structure assignments can be assessed Bioinformatic Glycomics, agreed that there is an urgent need to only if the relevant experimental parameters, computational develop infrastructure, including standardized protocols for the methods and underlying assumptions used to make the assign- exchange and reporting of structural glycan data and metadata to ments are described. In addition glycan analysis is often per- implement “a worldwide network of databases containing experi- formed not just using one method or technique but by utilizing mental and analytical data relevant to the structures and functions several orthogonal methods including array-based ligand- of glycans” (Packer et al. 2008). A subsequent NIH workshop binding assays, liquid chromatography (LC), CE, NMR, various organized by the Consortium for Functional Glycomics in 2009 typesofMSsuch asmassprofiling and tandem MS or hyphe- extended and refined these requirements, emphasizing the need to nated analytical methods such as GC–MS or LC–MS. Therefore, “Define specific criteria that make it possible for experts and non- any information derived from each technique used has to be experts to rapidly assess the depth and quality of a structural char- reported to provide a comprehensive and meaningful overview acterization that is described in a publication or structural database on the structure assignment, since each technique will provide entry.” (Workshop on Analytic and Bioinformatic Glycomics additional information consolidating the structural assignment or 2009). In July 2011, an international group of scientists attending illustrating exclusion of alternative structures. the 2nd Beilstein Symposium on Glyco-Bioinformatics in The MIRAGE guidelines provide a framework that allows this Potsdam (Germany) established the MIRAGE initiative under the information to be identified and presented in a consistent manner auspices of the Beilstein-Institut (http://www.beilstein-institut.de). in order to enhance the value of structural analyses that are disse- MIRAGE (i.e. the “Minimum Information Required for A minated by both scientific journals and databases. Scientificjour- Glycomics Experiment”) integrates worldwide efforts to develop nals can use the MIRAGE guidelines as the foundation for reporting guidelines for glycomics analytic data with the goal of developing their own checklists and guidelines for publishing facilitating the interpretation, evaluation and reproduction of these glycomics data. In fact, the recently published MIRAGE guide- data. These guidelines are intended to improve the quality of gly- lines for glycan analysis by MS (Kolarich et al. 2013)wereeval- comics datasets published in journals and stored in databases. uated by members of the glycobiology community (including Glycomics analysis offers unique challenges that necessitate representatives of several journals such as Glycobiology and reporting and archiving standards that are distinct from those Molecular and Cellular Proteomics (MCP)) at a workshop in already established for proteomics (such as the MIAPE standard; Athens, Georgia in August 2012 before establishing guidelines Taylor et al. 2007, 2008). The MIRAGE standards thus serve as for publishing mass spectral (MS) based glycomics data, later critical elements of the infrastructure required to integrate relevant called “Athens Guidelines” (Wells and Hart 2013) (see also scientific knowledge into a worldwide glycomics bioinformatics instructions to authors for Glycobiology). The MIRAGE guide- system capable of addressing diverse needs of the scientificcom- lines are not strictly enforced by the editors of MCP or munity. In this context, success of the MIRAGE project repre- Glycobiology, as the MIRAGE guidelines are considerably more sents a critical step toward fulfilling the recommendations of the 403 WS York et al. NAS Committee on Assessing the Importance and Impact of linked immuno-sorbent assays, saturation-transfer difference Glycomics and Glycosciences (Walt et al. 2012), which include NMR and isothermal titration calorimetry. the development of a “well-documented glycan structure data- The bioinformatics subgroup is charged with integrating data base that can be linked back to the original experimental data.” processing parameters into the guidelines for each laboratory method and defining separate guidelines for exchanging the in- formation defined in the guidelines between different software systems and databases. Coordination and consulting The second component of MIRAGE is the co-ordination group, which is concerned with the general organization of The MIRAGE project is steered by an international panel of meeting, community participation and dissemination of the scientists with expertise in diverse disciplines, including medi- documents to both the members of MIRAGE and the broader cinal and developmental glycobiology, carbohydrate chemistry, scientific community. The third component of MIRAGE is the glycoanalytics and glyco-bioinformatics, ensuring that the advisory board, which is composed of internationally recognized guidelines will encompass the most frequently used and rele- glycoscientists who support MIRAGE and have agreed to devote vant technologies. the time required to oversee the efforts of the first two groups. The MIRAGE project incorporates three organizational com- ponents: the working group, the coordinating group and the ad- visory board (Figure 1). The working group defines the tasks, makes general decisions and integrates detailed guidelines, Process of guideline development which are developed by subgroups focusing on structural ana- The aim of reporting guidelines is to support the scientific com- lysis, interaction analysis and bioinformatics. munity in publishing experimental data of high quality with The efforts of the structural analysis subgroup have already respect to integrity, comprehensiveness and reproducibility by led to the publication of guidelines for reporting glycoanalytic providing a framework to recommend details that should be mass spectral (MS) data (Kolarich et al. 2013). This guideline reported along with the data. It is critical for the success of has an organizational structure similar to that of the these guidelines that they do not appear to dictate how experi- MIAPE-MS guideline for proteins (Taylor et al. 2007) but the ments and analysis should be designed or implemented. In content is significantly different, addressing the specific order to gain general acceptance, MIRAGE thus shares several requirements of glycan analytics. Future work will encompass essential prerequisites with other guideline initiatives such as diverse sample preparation techniques and alternative techni- MIAPE (Taylor et al. 2007). These are: ques for the identification of glycan structures, such as LC, HPLC, CE or NMR. (i) Sufficiency: the guidelines should adequately describe The interaction analysis subgroup considers methods to define information about the experimental data and the experi- the biological interactions of glycans and glycoconjugates with mental conditions and methods used to generate the data other macromolecules, such as glycan-binding proteins, glycan- to enable individuals to understand, critically evaluate, potentiated signal receptors or microbes such as bacteria and interpret and reproduce the data. viruses. Initial efforts have focused on evaluating and describing (ii) Practicability: the guidelines should be concise, under- glycan microarray analyses and the data generated by these standable and limited to specific parameters that have a experiments. Future work will encompass diverse technologies significant effect on the outcome of an experiment, fa- such as surface plasmon resonance, flow cytometry, enzyme- cilitating compliance by scientists who use them. Fig. 1. MIRAGE incorporates three organizational components: the working group, the coordinating group and the advisory board. 404 Minimum information required for a glycomics experiment (iii) Stability: the guidelines must be stable over a time period Conclusion that is adequate to ensure consistency and comparability in The MIRAGE project has been established to define data report- data reporting. Nevertheless, the guidelines must accom- ing guidelines for glycomics databases and publications. They de- modate technical and scientific advances that should be scribe the essential information necessary to understand and considered when a new technique is sufficiently mature reproduce a glycomics experiment without dictating how the ex- and robust for widespread use. periment itself should be performed. Adoption of these guidelines by scientific journals in the form of checklists or additions to the author instructions will increase the quality and reproducibility of Scientific journals will play a crucial role in encouraging ac- the published results. In addition, adoption of the guidelines by ceptance of the guidelines by recommending that authors refer glycomics databases will facilitate methods for processing and to the guidelines when submitting their data. In many cases, the mining of the data produced by glycoanalytic experiments. status of the guidelines may change from a simple recommen- At the moment of writing this paper a guideline for glycomics dation to a requirement that must be considered by all partici- MS experiments has been released and published (Kolarich et al. pants in the publication process (including authors, reviewers, 2013). Further guidelines for other techniques used for glyco- curators and editors). mics experiments, such as glycan array experiments or LC separ- The development of a MIRAGE guideline is a multistep ation in combination with or without MS, are in currently in process. Maturation of the document through this process preparation and will be finished in summer 2014. increases its visibility and encourages consensus among Future activities of the MIRAGE project will be not just to stakeholders, facilitating its acceptance by the community. create guidelines for other types of experiments but also to Although this multistep development is time consuming and promote existing guidelines with scientific journals to accom- laborious, it has been proven to be an effective process for plish the integration of these guidelines by the journals. developing the MS guidelines (Kolarich et al. 2013), which have gained broad support from the MS and scientific pub- lishing communities. Funding The Beilstein-Institut, a non-profit foundation established under Transparency as a premise for a successful guideline civil law and located in Frankfurt am Main, Germany, has pro- proposition vided funding for advancement of the MIRAGE initiative. This work has also been supported by several other funding agen- The successful development and administration of any cies: DK and ER are both supported by the Max Planck reporting standard involves balancing specifications that are Society, and in addition, DK is funded by the Marie Curie grant sufficient to ensure the integrity and reproducibility of the PCIG09-GA-2011-293847. Both, ER and PMR have a grant reported data with the need for flexibility in designing and from the European Union’s Seventh Framework Programme implementing experiments and the free dissemination of (FP7-Health-F5-2011, grant agreement no 278535 “High valuable experimental results (Klipp et al. 2007). Any re- Glycan”); in addition, PMR has a grant from the European striction of scientific freedom regarding the generation or de- Union’s Seventh Framework Programme (FP7/2007-2013, scription of data should be avoided. Although scientific grant no. 259896); AD and SH are supported by the advances become valuable to the community only when new Biotechnology and Biological Sciences Research Council techniques and the data they generate are effectively commu- (grants BB/K016164/1 and BB/I017011/1); MC and NP are nicated to others, innovation required for such advances supported by the Australian Government project NeCTAR must not be stifled by standards aimed at improving the infor- financed by the Education Investment Fund; JZ and CC are mation content of scientificreports. supported by the NIH/NIGMS grant P41GM104603; WY, RR, With these human aspects in mind, it is clear that development MT and LW are supported as part of the NIH/NIGMS funded of the MIRAGE guidelines should be a highly transparent process National Center for Glycomics and Glycoproteomics that respects the viewpoints of the many different stakeholders and (8P41GM103490). NK’s contribution to this initiative is sup- thereby encourages maximum participation and continued support ported by The Swedish Foundation for International by the community. The parallel development of similar guidelines Cooperation in Research and Higher Education. TF and YL are by different groups would lead to confusion and must be avoided. supported by a Wellcome Trust Biomedical Resource grant Therefore, once a new MIRAGE guideline has been reviewed by WT099197MA. Funding to pay the Open Access publication the advisory committee, it is made available to the general public charges for this article was provided by Beilstein-Institut. via the MIRAGE project web site (http://glycomics.ccrc.uga.edu/ MIRAGE/index.php). This site also provides information about the mission and history of the MIRAGE group, along with References descriptions of the diverse projects and their progress. In addition, several hundred international researchers working on glycan ana- Klipp E, Liebermeister W, Helbig A, Kowald A, Schaber J. 2007. Nat. Biotech. 25:390. lysis, structure and function are proactively approached via email Kolarich D, Rapp E, Struwe WB, Haslam SM, Zaia J, McBride R, Agravat S, for advice, for example, to obtain feedback on draft versions of the Campbell MP, Kato M, Ranzinger R, et al. 2013. The minimum information guidelines. The MIRAGE committee recognizes the need for required for a glycomics experiment (MIRAGE) project – Improving the broadly based input, and welcomes all comments, advice and help standards for reporting mass spectrometry-based glycoanalytic data. Mol. in developing the guidelines. Cell Proteomics. 12:991–995. doi: 10.1074/mcp.O112.026492. 405 WS York et al. Packer NH, von der Lieth CW, Aoki-Kinoshita KF, Lebrilla CB, Paulson JC, information about a proteomics experiment (MIAPE). Nat. Biotechnol. Raman R, Rudd P, Sasisekharan R, Taniguchi N, York WS. 2008. Frontiers in 25:887–893. glycomics: Bioinformatics and biomarkers in disease. An NIH White Paper pre- Walt DA, Aoki-Kinoshita AF, Bendiak B, Bertozzi CR, Boons GJ, Darvill A, pared from discussions by the focus groups at a workshop on the NIH campus, Hart G, Kiessling LL, Lowe J, Moon RJ, et al. 2012. Transforming gly- Bethesda MD (September 11–13, 2006). Proteomics.8:8–20. coscience: A roadmap for the future. Washington, DC: The National Taylor CF, Field D, Sansone SA, Aerts J, Apweiler R, Ashburner M, Ball CA, Academies Press. http://www.ncbi.nlm.nih.gov/books/NBK109958/ Binz PA, Bogue M, Booth T, et al. 2008. Promoting coherent minimum Wells L, Hart GW. 2013. Glycomics: Building upon proteomics to advance reporting guidelines for biological and biomedical investigations: The glycosciences. Mol Cell Proteomics. 12:833–835. MIBBI project. Nat Biotechnol. 26:889–896. Workshop on Analytic and Bioinformatic Glycomics, Bethesda, MA, USA, Taylor CF, Paton NW, Lilley KS, Binz PA, Julian RK, Jr, Jones AR, Zhu W, April 16–18, 2009. http://glycomics.scripps.edu/SubgroupWorkshop/Work Apweiler R, Aebersold R, Deutsch EW, et al. 2007. The minimum shopApril2009Rpt.pdf. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Glycobiology Pubmed Central

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Pubmed Central
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© The Author 2014. Published by Oxford University Press.
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0959-6658
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1460-2423
DOI
10.1093/glycob/cwu018
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Abstract

Glycobiology vol. 24 no. 5 pp. 402–406, 2014 doi:10.1093/glycob/cwu018 Advance Access publication on March 20, 2014 MIRAGE: The minimum information required for a glycomics experiment 2 3 William S York , Sanjay Agravat , Kiyoko FAoki- diverse methods, including mass spectrometry (MS), 4 5,6 7 Kinoshita , Ryan McBride , Matthew P Campbell , chromatography, glycan array-binding assays, nuclear mag- 8 9 10 Catherine E Costello , Anne Dell , Ten Feizi , Stuart netic resonance (NMR) and other rapidly developing tech- 9 11 12 M Haslam , Niclas Karlsson , Kay-Hooi Khoo , nologies. The acceptance of these guidelines by scientists 13 10 14 Daniel Kolarich , Yan Liu , Milos Novotny , Nicolle conducting research on biological systems in which glycans 7 5,6 15 HPacker , James C Paulson , Erdmann Rapp , have a significant role will facilitate the evaluation and repro- 2 16 17 Rene Ranzinger , Pauline M Rudd , David F Smith , duction of glycomics experiments and data that is reported 18 2 2 Weston B Struwe , Michael Tiemeyer , Lance Wells , in scientific journals and uploaded to glycomics databases. 7 1,19 Joseph Zaia , and Carsten Kettner As a first step, MIRAGE guidelines for glycan analysis by 2 MS have been recently published (Kolarich D, Rapp E, Complex Carbohydrate Research Center, University of Georgia, 315 Struwe WB, Haslam SM, Zaia J., et al. 2013. The minimum Riverbend Road, Athens, GA 30602, USA; Center for Comprehensive Informatics, Emory University, 1784 N. Decatur Rd, Atlanta, GA 30322, USA; information required for a glycomics experiment (MIRAGE) Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 project – Improving the standards for reporting mass Tangi-machi, Hachioji, Tokyo 192-8577, Japan; Department of Cell and spectrometry-based glycoanalytic data. Mol. Cell Proteomics. Molecular Biology; Department of Physiological Chemistry, The Scripps 12:991–995), allowing them to be implemented and evaluated Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA; in the context of real-world glycobiology research. In this Biomolecular Frontiers Research Centre, Macquarie University, Sydney, NSW 2109, Australia; Center for Biomedical Mass Spectrometry, Department of paper, we set out the historical context, organization structure Biochemistry, Boston University, School of Medicine, 670 Albany Street, Suite and overarching objectives of the MIRAGE initiative. 504, Boston, MA 02118, USA; Department of Life Sciences, Imperial College London, London SW7 2AZ, UK; Glycosciences Laboratory Department of Medicine, Imperial College London, London W12 0NN, UK; Medical Biochemistry, University of Gothenburg, PO Box 440, 405 30 Gothenburg, Sweden; Institute of Biological Chemistry, Academia Sinica, 128, Academia Background Road Sec. 2, Nankang, Taipei 115, Taiwan; Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Advances in our ability to identify and quantify complex glycans Germany; Department of Chemistry, Indiana University, 800 E. Kirkwood 15 and glycoconjugates has led to an increasing awareness of the key Avenue, Bloomington, IN 47405, USA; Bioprocess Engineering, Max Planck roles that these molecules play in a wide range of physiological Institute for Dynamics of Complex Technical Systems, 39106 Magdeburg, Germany; NIBRT GlycoScience Group, NIBRT – National Institute for and pathological processes, including cell adherence, cell–cell Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, interactions, molecular trafficking, biosynthetic quality control, Blackrock, Co. Dublin, Ireland; Department of Biochemistry, School of signal transduction and host–pathogen recognition. Various types Medicine, Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA; of glycans and glycoconjugates are thus becoming recognized as Department of Chemistry, Chemistry Research Laboratory, University of essential participants in almost all biological processes. Structural Oxford, Oxford OX1 3TA, UK; and Beilstein-Institut, Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany analysis of glycoconjugates is technically challenging, requiring sophisticated analytical and computational techniques applied at The MIRAGE (minimum information required for a glyco- the interface of biology and chemistry. Although recent technical mics experiment) initiative was founded in Seattle, WA, in advances in this area have led to the emergence of glycomics as a November 2011 in order to develop guidelines for reporting distinct discipline, progress is slowed by the unavailability of the qualitative and quantitative results obtained by diverse robust, generally applicable software tools required to process, an- types of glycomics analyses, including the conditions and tech- notate, archive and mine the data now being generated in this niques that were applied to prepare the glycans for analysis domain. and generate the primary data along with the tools and para- The complexity of glycans and the diversity of their structures meters that were used to process and annotate this data. and molecular contexts have necessitated the development of a These guidelines must address a broad range of issues, as gly- wide range of experimental techniques and instrumentation for comics data are inherently complex and are generated using their analysis. Although mass spectrometry (MS) is the most fre- quently applied methodology for glycan analysis, array-based ligand-binding assays, high-performance liquid chromatography, capillary electrophoresis (CE), nuclear magnetic resonance To whom correspondence should be addressed: Tel: +49-(0)69-7167-3221; Fax: +49-(0)69-7167-3219; e-mail: ckettner@beilstein-institut.de (NMR) and several other techniques are now being routinely © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by- nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 402 Minimum information required for a glycomics experiment used for this purpose. Recent advances in analytical method- detailed than the Athens Guidelines. However, the two sets of ology and instrumentation make it possible to produce glycomics guidelines are mutually consistent and complementary. data with increased depth, speed and efficiency, resulting in the The MIRAGE guidelines provide reviewers with specific, generation of extremely large and diverse datasets. However, the technical descriptions of the metadata required to evaluate the reporting and/or distribution of information obtained during a glycomics analysis, and can thus be used by a qualified review- glycomics experiment pose unique challenges to the analyst. er as a basis for making judgments regarding the validity of This includes the identification and presentation of relevant specific conclusions in the manuscript. However, they are not metadata that allows the results to be objectively evaluated and intended to substitute for the review process itself or to define interpreted in a biological context and reproduced in the labora- acceptance criteria for submitted manuscripts. tories of other scientists. The criteria for acceptance of glycomics data for inclusion It is important to note that glycomics cannot be viewed as a into a database are likely to be somewhat different than those straightforward extension of proteomics. Glycomics and pro- for acceptance in a scientific journal. For example, the curator- teomics experiments share the same basic goal, i.e. the identifi- ial process for inclusion of a dataset in a database may not cation and quantification (where possible) of specific molecular include review by an expert. In such cases, rigorous guidelines structures in a particular biological context. However, the com- for the inclusion of metadata are crucial, as these metadata are a plex and often branched structures of glycans, in combination necessary prerequisite for the (automated or manual) selection with the non-template-driven mechanisms leading to their bio- of relevant, trusted data from the database for comparison to synthesis, have made the emergence of glycomics as a discip- new datasets or inclusion in data-mining investigations. We line dependent on the ongoing development of new analytical expect that the MIRAGE guidelines (developed by analysts, approaches and computational tools that are not required for pro- biologists and bioinformaticians with glycomics expertise) will teomics. The quality and information content of the annotated serve as a convenient foundation to define the information that data generated by such tools can vary considerably, depending has to be stored in a database to provide comprehensive and re- on the exact experimental conditions used to generate primary producible datasets to its users. data, the suitability and configuration of the computational tools used to process this data, the quality of any databases that are invoked during the data processing and the validity of any MIRAGE assumptions that are made when assigning glycan structures in the presence of incomplete analytical data. In 2006, participants at the Workshop on Analytical and The validity of glycan structure assignments can be assessed Bioinformatic Glycomics, agreed that there is an urgent need to only if the relevant experimental parameters, computational develop infrastructure, including standardized protocols for the methods and underlying assumptions used to make the assign- exchange and reporting of structural glycan data and metadata to ments are described. In addition glycan analysis is often per- implement “a worldwide network of databases containing experi- formed not just using one method or technique but by utilizing mental and analytical data relevant to the structures and functions several orthogonal methods including array-based ligand- of glycans” (Packer et al. 2008). A subsequent NIH workshop binding assays, liquid chromatography (LC), CE, NMR, various organized by the Consortium for Functional Glycomics in 2009 typesofMSsuch asmassprofiling and tandem MS or hyphe- extended and refined these requirements, emphasizing the need to nated analytical methods such as GC–MS or LC–MS. Therefore, “Define specific criteria that make it possible for experts and non- any information derived from each technique used has to be experts to rapidly assess the depth and quality of a structural char- reported to provide a comprehensive and meaningful overview acterization that is described in a publication or structural database on the structure assignment, since each technique will provide entry.” (Workshop on Analytic and Bioinformatic Glycomics additional information consolidating the structural assignment or 2009). In July 2011, an international group of scientists attending illustrating exclusion of alternative structures. the 2nd Beilstein Symposium on Glyco-Bioinformatics in The MIRAGE guidelines provide a framework that allows this Potsdam (Germany) established the MIRAGE initiative under the information to be identified and presented in a consistent manner auspices of the Beilstein-Institut (http://www.beilstein-institut.de). in order to enhance the value of structural analyses that are disse- MIRAGE (i.e. the “Minimum Information Required for A minated by both scientific journals and databases. Scientificjour- Glycomics Experiment”) integrates worldwide efforts to develop nals can use the MIRAGE guidelines as the foundation for reporting guidelines for glycomics analytic data with the goal of developing their own checklists and guidelines for publishing facilitating the interpretation, evaluation and reproduction of these glycomics data. In fact, the recently published MIRAGE guide- data. These guidelines are intended to improve the quality of gly- lines for glycan analysis by MS (Kolarich et al. 2013)wereeval- comics datasets published in journals and stored in databases. uated by members of the glycobiology community (including Glycomics analysis offers unique challenges that necessitate representatives of several journals such as Glycobiology and reporting and archiving standards that are distinct from those Molecular and Cellular Proteomics (MCP)) at a workshop in already established for proteomics (such as the MIAPE standard; Athens, Georgia in August 2012 before establishing guidelines Taylor et al. 2007, 2008). The MIRAGE standards thus serve as for publishing mass spectral (MS) based glycomics data, later critical elements of the infrastructure required to integrate relevant called “Athens Guidelines” (Wells and Hart 2013) (see also scientific knowledge into a worldwide glycomics bioinformatics instructions to authors for Glycobiology). The MIRAGE guide- system capable of addressing diverse needs of the scientificcom- lines are not strictly enforced by the editors of MCP or munity. In this context, success of the MIRAGE project repre- Glycobiology, as the MIRAGE guidelines are considerably more sents a critical step toward fulfilling the recommendations of the 403 WS York et al. NAS Committee on Assessing the Importance and Impact of linked immuno-sorbent assays, saturation-transfer difference Glycomics and Glycosciences (Walt et al. 2012), which include NMR and isothermal titration calorimetry. the development of a “well-documented glycan structure data- The bioinformatics subgroup is charged with integrating data base that can be linked back to the original experimental data.” processing parameters into the guidelines for each laboratory method and defining separate guidelines for exchanging the in- formation defined in the guidelines between different software systems and databases. Coordination and consulting The second component of MIRAGE is the co-ordination group, which is concerned with the general organization of The MIRAGE project is steered by an international panel of meeting, community participation and dissemination of the scientists with expertise in diverse disciplines, including medi- documents to both the members of MIRAGE and the broader cinal and developmental glycobiology, carbohydrate chemistry, scientific community. The third component of MIRAGE is the glycoanalytics and glyco-bioinformatics, ensuring that the advisory board, which is composed of internationally recognized guidelines will encompass the most frequently used and rele- glycoscientists who support MIRAGE and have agreed to devote vant technologies. the time required to oversee the efforts of the first two groups. The MIRAGE project incorporates three organizational com- ponents: the working group, the coordinating group and the ad- visory board (Figure 1). The working group defines the tasks, makes general decisions and integrates detailed guidelines, Process of guideline development which are developed by subgroups focusing on structural ana- The aim of reporting guidelines is to support the scientific com- lysis, interaction analysis and bioinformatics. munity in publishing experimental data of high quality with The efforts of the structural analysis subgroup have already respect to integrity, comprehensiveness and reproducibility by led to the publication of guidelines for reporting glycoanalytic providing a framework to recommend details that should be mass spectral (MS) data (Kolarich et al. 2013). This guideline reported along with the data. It is critical for the success of has an organizational structure similar to that of the these guidelines that they do not appear to dictate how experi- MIAPE-MS guideline for proteins (Taylor et al. 2007) but the ments and analysis should be designed or implemented. In content is significantly different, addressing the specific order to gain general acceptance, MIRAGE thus shares several requirements of glycan analytics. Future work will encompass essential prerequisites with other guideline initiatives such as diverse sample preparation techniques and alternative techni- MIAPE (Taylor et al. 2007). These are: ques for the identification of glycan structures, such as LC, HPLC, CE or NMR. (i) Sufficiency: the guidelines should adequately describe The interaction analysis subgroup considers methods to define information about the experimental data and the experi- the biological interactions of glycans and glycoconjugates with mental conditions and methods used to generate the data other macromolecules, such as glycan-binding proteins, glycan- to enable individuals to understand, critically evaluate, potentiated signal receptors or microbes such as bacteria and interpret and reproduce the data. viruses. Initial efforts have focused on evaluating and describing (ii) Practicability: the guidelines should be concise, under- glycan microarray analyses and the data generated by these standable and limited to specific parameters that have a experiments. Future work will encompass diverse technologies significant effect on the outcome of an experiment, fa- such as surface plasmon resonance, flow cytometry, enzyme- cilitating compliance by scientists who use them. Fig. 1. MIRAGE incorporates three organizational components: the working group, the coordinating group and the advisory board. 404 Minimum information required for a glycomics experiment (iii) Stability: the guidelines must be stable over a time period Conclusion that is adequate to ensure consistency and comparability in The MIRAGE project has been established to define data report- data reporting. Nevertheless, the guidelines must accom- ing guidelines for glycomics databases and publications. They de- modate technical and scientific advances that should be scribe the essential information necessary to understand and considered when a new technique is sufficiently mature reproduce a glycomics experiment without dictating how the ex- and robust for widespread use. periment itself should be performed. Adoption of these guidelines by scientific journals in the form of checklists or additions to the author instructions will increase the quality and reproducibility of Scientific journals will play a crucial role in encouraging ac- the published results. In addition, adoption of the guidelines by ceptance of the guidelines by recommending that authors refer glycomics databases will facilitate methods for processing and to the guidelines when submitting their data. In many cases, the mining of the data produced by glycoanalytic experiments. status of the guidelines may change from a simple recommen- At the moment of writing this paper a guideline for glycomics dation to a requirement that must be considered by all partici- MS experiments has been released and published (Kolarich et al. pants in the publication process (including authors, reviewers, 2013). Further guidelines for other techniques used for glyco- curators and editors). mics experiments, such as glycan array experiments or LC separ- The development of a MIRAGE guideline is a multistep ation in combination with or without MS, are in currently in process. Maturation of the document through this process preparation and will be finished in summer 2014. increases its visibility and encourages consensus among Future activities of the MIRAGE project will be not just to stakeholders, facilitating its acceptance by the community. create guidelines for other types of experiments but also to Although this multistep development is time consuming and promote existing guidelines with scientific journals to accom- laborious, it has been proven to be an effective process for plish the integration of these guidelines by the journals. developing the MS guidelines (Kolarich et al. 2013), which have gained broad support from the MS and scientific pub- lishing communities. Funding The Beilstein-Institut, a non-profit foundation established under Transparency as a premise for a successful guideline civil law and located in Frankfurt am Main, Germany, has pro- proposition vided funding for advancement of the MIRAGE initiative. This work has also been supported by several other funding agen- The successful development and administration of any cies: DK and ER are both supported by the Max Planck reporting standard involves balancing specifications that are Society, and in addition, DK is funded by the Marie Curie grant sufficient to ensure the integrity and reproducibility of the PCIG09-GA-2011-293847. Both, ER and PMR have a grant reported data with the need for flexibility in designing and from the European Union’s Seventh Framework Programme implementing experiments and the free dissemination of (FP7-Health-F5-2011, grant agreement no 278535 “High valuable experimental results (Klipp et al. 2007). Any re- Glycan”); in addition, PMR has a grant from the European striction of scientific freedom regarding the generation or de- Union’s Seventh Framework Programme (FP7/2007-2013, scription of data should be avoided. Although scientific grant no. 259896); AD and SH are supported by the advances become valuable to the community only when new Biotechnology and Biological Sciences Research Council techniques and the data they generate are effectively commu- (grants BB/K016164/1 and BB/I017011/1); MC and NP are nicated to others, innovation required for such advances supported by the Australian Government project NeCTAR must not be stifled by standards aimed at improving the infor- financed by the Education Investment Fund; JZ and CC are mation content of scientificreports. supported by the NIH/NIGMS grant P41GM104603; WY, RR, With these human aspects in mind, it is clear that development MT and LW are supported as part of the NIH/NIGMS funded of the MIRAGE guidelines should be a highly transparent process National Center for Glycomics and Glycoproteomics that respects the viewpoints of the many different stakeholders and (8P41GM103490). NK’s contribution to this initiative is sup- thereby encourages maximum participation and continued support ported by The Swedish Foundation for International by the community. The parallel development of similar guidelines Cooperation in Research and Higher Education. TF and YL are by different groups would lead to confusion and must be avoided. supported by a Wellcome Trust Biomedical Resource grant Therefore, once a new MIRAGE guideline has been reviewed by WT099197MA. Funding to pay the Open Access publication the advisory committee, it is made available to the general public charges for this article was provided by Beilstein-Institut. via the MIRAGE project web site (http://glycomics.ccrc.uga.edu/ MIRAGE/index.php). This site also provides information about the mission and history of the MIRAGE group, along with References descriptions of the diverse projects and their progress. In addition, several hundred international researchers working on glycan ana- Klipp E, Liebermeister W, Helbig A, Kowald A, Schaber J. 2007. Nat. Biotech. 25:390. lysis, structure and function are proactively approached via email Kolarich D, Rapp E, Struwe WB, Haslam SM, Zaia J, McBride R, Agravat S, for advice, for example, to obtain feedback on draft versions of the Campbell MP, Kato M, Ranzinger R, et al. 2013. The minimum information guidelines. The MIRAGE committee recognizes the need for required for a glycomics experiment (MIRAGE) project – Improving the broadly based input, and welcomes all comments, advice and help standards for reporting mass spectrometry-based glycoanalytic data. Mol. in developing the guidelines. Cell Proteomics. 12:991–995. doi: 10.1074/mcp.O112.026492. 405 WS York et al. Packer NH, von der Lieth CW, Aoki-Kinoshita KF, Lebrilla CB, Paulson JC, information about a proteomics experiment (MIAPE). Nat. Biotechnol. Raman R, Rudd P, Sasisekharan R, Taniguchi N, York WS. 2008. Frontiers in 25:887–893. glycomics: Bioinformatics and biomarkers in disease. An NIH White Paper pre- Walt DA, Aoki-Kinoshita AF, Bendiak B, Bertozzi CR, Boons GJ, Darvill A, pared from discussions by the focus groups at a workshop on the NIH campus, Hart G, Kiessling LL, Lowe J, Moon RJ, et al. 2012. Transforming gly- Bethesda MD (September 11–13, 2006). Proteomics.8:8–20. coscience: A roadmap for the future. Washington, DC: The National Taylor CF, Field D, Sansone SA, Aerts J, Apweiler R, Ashburner M, Ball CA, Academies Press. http://www.ncbi.nlm.nih.gov/books/NBK109958/ Binz PA, Bogue M, Booth T, et al. 2008. Promoting coherent minimum Wells L, Hart GW. 2013. Glycomics: Building upon proteomics to advance reporting guidelines for biological and biomedical investigations: The glycosciences. Mol Cell Proteomics. 12:833–835. MIBBI project. Nat Biotechnol. 26:889–896. Workshop on Analytic and Bioinformatic Glycomics, Bethesda, MA, USA, Taylor CF, Paton NW, Lilley KS, Binz PA, Julian RK, Jr, Jones AR, Zhu W, April 16–18, 2009. http://glycomics.scripps.edu/SubgroupWorkshop/Work Apweiler R, Aebersold R, Deutsch EW, et al. 2007. The minimum shopApril2009Rpt.pdf.

Journal

GlycobiologyPubmed Central

Published: Mar 20, 2014

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