- Carbohydrates in diagnosis and therapy
- Bridging the gap between analysis and storage of glycan data
- Structure–function relationships of carbohydrates
Unravelling Glycan Complexity
Beilstein Glyco-Bioinformatics Symposium 2015
22 – 26 June 2015
avendi-Hotel am Griebnitzsee, Potsdam, Germany
Scientific Organizers: Carsten Kettner, Martin Hicks and Peter Seeberger
The Glyco-Bioinformatics Symposium 2015 brought together glycochemists and biologists with experts in bioinformatics and computer sciences. The Scientific Program was very well attended and the speakers addressed a wide range of topics to draw a comprehensive picture of the complexity of glycans.
- Carbohydrate–protein interaction and glycoarrays
- Integration of glycomics with other -omics fields
- Software tools for analysis and data mining
As a distinct discipline glycomics has gained significant impact over the past decade. The proteomics and genomics communities increasingly perceive glycans as essential elements in physiological and pathological processes rather than as decorative elements of lipids and proteins.
Glycans are extremely complex and diverse in their structures and thus it has been necessary to develop a wide range of experimental techniques and instrumentation for their detection and analysis. With the advancement of techniques for the interactive and structural analysis of glycoconjugates their essential role in phenomena such as cell adherence, cell–cell interactions, molecular trafficking, biosynthetic quality control, signal transduction and host–pathogen recognition, became apparent.
However, analysis and interpretation using computational means could not keep step with the experimental and technical advances due to the initial lack of applicable software tools which are required for processing, annotating, storing and mining of data. In addition, the validation of glycan structure assignments is impeded by a common reporting procedure which does not allow for the comprehensive description of relevant experimental parameters, computational methods and underlying assumptions. This in turn makes the successful annotation of data from the literature as well as mining in databases an uncertain endeavor and furthermore hampers interpretation and reproduction of this data.
The Beilstein Glyco-Bioinformatics Symposia bring together glycochemists and biologists with experts in bioinformatics and computer sciences to lay the foundation for a concerted effort in establishing the area of glyco-bioinformatics. The previous symposia brought the stakeholders in the area of glycomics together and provided a platform to discuss the role of bioinformatics in this emerging field. One important outcome was the founding of a new working group called MIRAGE (Minimum Information Required for a Glycomics Experiment) which is under the auspices of the Beilstein-Institut. With the involvement of the scientific community this group of internationally renowned scientists develops publication guidelines for the reporting of glycomics data as well as data exchange formats with the aim of setting up a framework to integrate glyco-bioinformatics in a comprehensive platform that will serve biologists, chemists and all interested in glycosciences.
This symposium aims to bring together scientists that “produce” the data with those scientists that “use” the data and make it available to the community. In particular, speakers of the symposia will contribute to unravel the complexity of glycans and deliver insights into the diverse physiological and structural manifestations of sugars by covering aspects such as: carbohydrates in diagnosis and therapy, bridging the gap between analysis and storage of glycan data, structure–function relationships of carbohydrates, carbohydrate–protein interaction and glycoarrays and software tools for analysis and data mining.
by Weston B. Struwe, University of Oxford, UK
The 4th Beilstein Glyco-Bioinformatics Symposium took place in Potsdam, Germany, and addressed several key issues facing the field of glycobiology. Presentations covered a range of disciplines from biology to computer science which provided a unique venue to discuss these challenges through an interdisciplinary approach. Researchers were offered an opportunity to not only present new research but also a unique environment to converse with other experts in the field and promote collaborations worldwide. The unique style of the Beilstein Symposia fosters a comfortable atmosphere which only furthers the exchange of ideas, knowledge and expertise to advance research in the glycosciences.
The 2015 meeting was entitled Unravelling Glycan Complexity and brought together chemists, biologists, bioinformaticians and computer scientists from 16 countries to promote the area of glyco-informatics. Presentations were innovative and highlighted key findings that emphasised the importance of glycan three-dimensional structure as it relates to interacting partners, appreciation for indistinct and dynamic genetic factors that contribute to systems glycobiology, understanding challenges and limitations in existing analytical methods and in oligosaccharide synthesis as well as demonstrations of the latest bioinformatics tools. Glycomics remains an important subject area among other –OMICS fields and its continued success is driven by pioneering and progressing research which was reflected in this year’s meeting.
The Glyco-Bioinformatics Symposia focus on contemporary analytical challenges in glycoscience and aims to address important needs among researchers. This year the stage was brilliantly set by the inaugural talk from Hans Vliegenthart who not only discussed the fine details of glycan structures but also how they relate to non-glycan moieties and the significance of glycoconjugate presentation. The importance of structure in a range of biological processes and the ability to dissect glycoconjugate structures, particularly by mass spectrometry, was further iterated in talks by Anne Dell, Joe Zaia, Catherine Costello, Peter Hufnagel and Kevin Pagel. Current capabilities, limitations and accurate data interpretation were emphasized as well as a comprehensive assessment of novel techniques, including ion mobility, new dissociation modes, high-resolution analysis and MS-imaging provided an excellent outlook for enhanced methods.
The discussions of glycan structure-function relationships continued through a series of talks examining carbohydrate interactions monitored by glycan/lectin microarrays and associated considerations in their design. Peter Seeberger discussed modern commercially available automated synthesis platforms and Todd Lowary described “boutique” arrays that accurately represent glycan structures used for diagnostics. The use of shotgun glycan microarrays and the incorporation of existing metadata derived from genetic and/or structural analyses, termed metadata-assisted glycan sequencing (MAGS), was presented by David Smith which aids to more accurately characterize glycan binders.
Glycan recognition in a range of biological systems from drug design to predicting glycan binding of bacterial proteins was presented, but interestingly underlying each talk was the application of innovative strategies to interrogate these interactions. The use of molecular dynamics to probe the effects of glycan conformation and protein desolvation in bacterial adhesion was presented by Stefani Barbirz revealing how water can fine tune complex formation. The design and development of carbohydrate mimics for successfully targeting so-called “undruggable target” lectins was described by Beat Ernst and showed how high-affinity antagonists can be designed to inhibit difficult targets in a series of human diseases. The development and application of Metabolic Sia Engineering (MSE) from Rüdiger Horstkorte showed how cellular uptake and incorporation of synthetic precursors disrupts polysialylation which has potential for cancer treatment.
Adam Godzik presented how homology modelling and understanding protein networks can be used to discover new glycan processing enzymes and carbohydrate binding models on bacterial cell surfaces.
The application of surface plasma resonance imaging (SPRi) towards deciphering the molecular mechanisms between cell-surface glycosaminoglycans and target proteins was described by Sylvie Ricard-Blum. These interaction networks are curated in the MatrixDB database and focuses on extracellular matrix components. Jim Paulson presented the development and use of sialic acid coated liposomes with high-affinity to certain immune cells capable of stimulating target cells or delivery of chemo-therapeutic drugs.
Realizing glycan modifications and the interplay with proteomics/genomics is on the forefront of glycomics and several talks described these systems-based approaches. Lara Mahal explained how the use of lectin microarrays, data integration and microRNA network analysis of (glyco)gene expression may be used to predict regulation and interrogate the glycome. Work from Pauline Rudd illustrated how high-throughput glycan analysis in conjunction with genome-wide association studies can delineate genome-glycome relationships. The interplay of glycosylation and DNA transcription was further discussed by Gerry Hart in studies of O-GlcNAc modifications and the relationship with phosphorylation in diabetes.
Ultimately, the continued success of glycobiology hinges on these pioneering methods capable of interrogating glycan structure-function relationships in cellular processes but is also underpinned by inventive computational tools to fully grasp these complex datasets. Several talks explained the latest developments in software tools and databases tailored specifically for existing analytical methods. Nicki Packer compared existing genomics and proteomics tools currently available and how the glycomics community can improve and link existing databases. The importance of developers working together with researchers to ensure the success of new tools was stressed as well as the merits of data sharing and cross-referencing datasets. Kiyoko Aoki-Kinoshita presented the Integrated Database Project of Japan as well as GlyTouCan, a glycan structure repository with unique accession numbers assigned to known glycan structures. Furthermore, the recent formation of GlycoRDF, a standardized ontology for storing glycan related data in RDF (Resource Description Framework) format was described which was also highlighted throughout the meeting.
René Ranzinger expressed the need for a common infrastructure and also current problems in glyco-bioinformatics including what information ought to be stored, how to support software development and the existence of common support funds. Will York talked about implications in quantitative data analysis and the use of REQUIEM (RElative QUantitation Including Everything Meaningful) analysis for comparative analysis between samples.
René Ranzinger, Will York and Carsten Kettner presented an update of the Minimal Information Required for a Glycomics Experiment (MIRAGE) Project designed to help facilitate the reproducibility of glycomics experiments through reporting guidelines in scientific journals and promote the implementation of congruent data formats to be adopted worldwide.
The Beilstein Glyco-Bioinformatics Symposia provokes discussions on current issues in glycoscience and challenges attendees how to tackle these needs among researchers with an emphasis on bioinformatics.The outlook for the development of dedicated repositories and tools to interrogate glycomics datasets has widely been realized by the glycomics community. This sentiment was recently echoed in the detailed 2012 report from the National Academy of Sciences entitled Transforming Glycoscience: A Roadmap for the Future. The Beilstein-Institut has been at the forefront of this effort having hosted the bi-annual Glyco-Bioinformatics Symposia since 2009. As by design the beautiful setting of the symposia helped stimulate discussions outside the oral and poster sessions, which without doubt cultivated new relationships that will spur continued growth in the field for years to come.
Tuesday, 23 June
The Definition of Glycan Structures
Hans Vliegenthart, Utrecht University
Anne Dell, Imperial College London
Poster Session #1
(Posters 1 - 3)
Nutrient Sensing by O-GlcNAcylation Modulates Nearly All Aspects of Cellular Physiology
Gerald Hart, Johns Hopkins University
The MIRAGE Presentation
The MIRAGE Working group
Sweet Systems: Mapping the Glycome Using Systems-based Approaches
Lara Mahal, New York University
Glycan Array and Other Tools Produced by Automated Glycan Assembly
Peter Seeberger, MPI of Colloids and Interfaces
On Defining a Human Metaglycome Using Automated Metadata Glycan Sequencing (MAGS) on Shotgun Glycan Microarrays
David Smith, Emory University
Poster Session #2
(Posters 4 - 6)
'Boutique' Glycan Arrays as Research Tools and Diagnostics
Todd Lowary, University of Alberta
Sialic Acid Metabolic Engineering: A Potential Strategy for Cancer Therapy
Rüdiger Horstkorte, Universität Halle-Wittenberg
Sofware Session #1
(Presentations 1 - 3)
Wednesday, 24 June
Latest Development in Semantic Web Technologies Applied to Glycosciences
Kiyoko Aoki-Kinoshita, Soka University
From Glycoanalytics to Glycostructures to Glycoknowledge
Nicolle Packer, Macquarie University
A Common Glyco-Bioinformatics Infrastructure
René Ranzinger, Univeristy of Georgia
Poster Session #3
(Posters 7 - 12)
State-of-the-Art Glycoanalytics for Big Data Sets, Biomarker Discovery and the Pharmaceutical Industry
Pauline Rudd, NIBRT
Bioinformatics for Integrated omics of Glycans and Glycoproteins
Joe Zaia, Boston University
Thursday, 25 June
The Need for Expandable Formats and Tools for MS in Glycan Databases
Catherine Costello, Boston University
Teaching an Old Dog New Tricks
Will York, University of Georgia
Improving N- and O-glycopeptide Identification by LC-MSMS: A Systematic Investigation of CID Q-TOF-MS/MS Collision Energies
Peter Hufnagel, Bruker Daltonik GmbH
Separation of Carbohydrate and Glycoprotein Isomers Using Ion Mobility MS
Kevin Pagel, Free University Berlin
Structure-function Studies of Glycans Using MS
Sabine Flitsch, The University of Manchester
Software Session #2
(Presentations 4 - 6)
Complex Carbohydrate Recognition by Proteins: Fundamental Insights from Bacteriophage Cell Adhesion Systems
Stefanie Barbirtz, University of Potsdam
Targeting Immune Cells with Siglec Ligand Decorated Nanoparticles
James Paulson, The Scripps Research Institute
Druggability of Lectins - Mission Possible?
Beat Ernst, University of Basel
Software Session #3
(Presentations 7 and 8)
Domain and Fold Repertoire View of Bacteroides Adaptation to Carbohydrate Rich Environment
Adam Godzik, Sanford-Burnham Medical Research Institute
Protein-glycosaminoglycan Interaction Networks: Focus on Heparan Sulfate
Sylvie Ricard-Blum, Université Lyon
Oral Poster and Software Presentations
Siglec-8 – A Novel Target For Asthma
Blijke Kroezen, University of Basel
Elucidation of Molecular Mechanisms Behind the Interaction of Sulfated Hyaluronan with TGF-ß1 by In Silico and Experimental Approaches
Sergey Samsonov, TU Dresden
Preparation and Antixoidant Activity of Chitooligosaccharides Composed of Well-defined Glucosamine and N-acetoylglucosamine Units
Li Kecheng, Chinese Academy of Sciences, Qingdao
Mucin-type O-glycans Regulate Adipose Tissue-derived Stem Cells Differentiation and Peripheral Nerve Regeneration
Wen-Chieh Liao, Chung Shan Medical University, Taichung, China
Bacteriophage Tailspikes as Carbohydrate Binding Proteins in Experimental and Computational Approaches to Analyze Binding Affinities
Sonja Kunstmann, University of Potsdam
Identification of Isomeric Carbohydrates - Collision Cross Section Fingerprinting
Johanna Hofmann, Fritz Haber Institute of the Max Planck Society, Berlin
Usage of the GRITS Toolbox for the Interpretation of Glycomic Mass Spectrometric Data
D. Brent Weatherly, University of Georgia, Athens, USA
Higher Order Structure and Encoding of Mass Spectrometry Data for High-throughput Human Fc IgG N-glycosylation Analysis
Genadij Razdorov, University of Zagreb
Carbohydrate 3D Structures in the Protein Data Bank: a 2015 Update
Thomas Lütteke, University of Giessen
Screening O-Antigen Variants in Bacterial Strains by an ELISA-like Tailspike-adsorption Assay
Andreas Schmidt, University of Potsdam
Normalization and Batch Correction Methods for High-throughput Glycomics
Frano Vuckovic, Genos, Zagreb
A Simple Combinatorial Approach to Identify O-linked Glycosylation Patterns from Intact Protein Masses Determined by Mass Spectrometry
Stefan Senn, University of Salzburg
GlycoMarker: a Web Application to Extract Disease Biomarkers from Liquid Chromatography Profiles
Ian Walsh, NIBRT, Dublin
Integrated –Omics Approach to Glycoproteomics
Josh Klein, Boston University
Modular Synthesis System as a Tool to Explore the Glycogalaxy /
Infrastructure for an Extensible Synthesis Language and Chemical Quality Management
Frank Schuhmacher, Max Planck Institute of Colloids and Interfaces, Potsdam
SugarBind, the Pathogen Lectin-glycan Interaction Database
Julien Mariethoz, Swiss Institute of Bioinformatics, Geneva
MassyTools: A Data Processing Tool for High-throughput MALDI-MS Glycomics
Bas Jansen, Leiden University Medical Center, The Netherlands
Tackling the Challenge of Structure Searching Building: New Tools Powered by GlycoRDF
Matthew Campbell, Macquarie University, Sydney
An E-workflow for Glycoanalyitical Mass Spectrometric Data
Miguel Rojas-Macias, University of Gothenborg, Sweden
Characterization of Glycan Recognition by the Anti-HIV Lectins BanLec and Griffithsin by Native Mass Spectrometry
Weston Struwe, University of Oxford