Examining and Fine-tuning the Selection of Glycan Compositions with GlyConnect Compozitor

Abstract

A key point in achieving accurate intact glycopeptide identification is the definition of the glycan composition file that is used to match experimental with theoretical masses by a glycoproteomics search engine. At present, these files are mainly built from searching the literature and/or querying data sources focused on posttranslational modifications. Most glycoproteomics search engines include a default composition file that is readily used when processing MS data. We introduce here a glycan composition visualizing and comparative tool associated with the GlyConnect database and called GlyConnect Compozitor. It offers a web interface through which the database can be queried to bring out contextual information relative to a set of glycan compositions. The tool takes advantage of compositions being related to one another through shared monosaccharide counts and outputs interactive graphs summarizing information searched in the database. These results provide a guide for selecting or deselecting compositions in a file in order to reflect the context of a study as closely as possible. They also confirm the consistency of a set of compositions based on the content of the GlyConnect database. As part of the tool collection of the [email protected] initiative, Compozitor is hosted at https://glyconnect.expasy.org/compozitor/ where it can be run as a web application. It is also directly accessible from the GlyConnect database. A key point in achieving accurate intact glycopeptide identification is the definition of the glycan composition file that is used to match experimental with theoretical masses by a glycoproteomics search engine. At present, these files are mainly built from searching the literature and/or querying data sources focused on posttranslational modifications. Most glycoproteomics search engines include a default composition file that is readily used when processing MS data. We introduce here a glycan composition visualizing and comparative tool associated with the GlyConnect database and called GlyConnect Compozitor. It offers a web interface through which the database can be queried to bring out contextual information relative to a set of glycan compositions. The tool takes advantage of compositions being related to one another through shared monosaccharide counts and outputs interactive graphs summarizing information searched in the database. These results provide a guide for selecting or deselecting compositions in a file in order to reflect the context of a study as closely as possible. They also confirm the consistency of a set of compositions based on the content of the GlyConnect database. As part of the tool collection of the [email protected] initiative, Compozitor is hosted at https://glyconnect.expasy.org/compozitor/ where it can be run as a web application. It is also directly accessible from the GlyConnect database. One of the most interesting current challenges in proteomics research is estimating the extent of protein diversity as recently summarized in (1Aebersold R. Agar J.N. Amster I.J. Baker M.S. Bertozzi C.R. Boja E.S. Costello C.E. Cravatt B.F. Fenselau C. Garcia B.A. Ge Y. Gunawardena J. Hendrickson R.C. Hergenrother P.J. Huber C.G. Ivanov A.R. Jensen O.N. Jewett M.C. Kelleher N.L. Kiessling L.L. Krogan N.J. Larsen M.R. Loo J.A. Ogorzalek Loo R.R. Lundberg E. MacCoss M.J. Mallick P. Mootha V.K. Mrksich M. Muir T.W. Patrie S.M. Pesavento J.J. Pitteri S.J. Rodriguez H. Saghatelian A. Sandoval W. Schlüter H. Sechi S. Slavoff S.A. Smith L.M. Snyder M.P. Thomas P.M. Uhlén M. Van Eyk J.E. Vidal M. Walt D.R. White F.M. Williams E.R. Wohlschlager T. Wysocki V.H. Yates N.A. Young N.L. Zhang B. How many human proteoforms are there?.Nat. Chem. Biol. 2018; 14: 206-214Crossref PubMed Scopus (363) Google Scholar). To encompass all molecular forms of a protein following genetic variation, alternative splicing and posttranslational processing, the term “proteoform” was recently proposed (2Smith L.M. Kelleher N.L. Consortium for Top Down Proteomics Proteoform: a single term describing protein complexity.Nat. Methods. 2013; 10: 186-187Crossref PubMed Scopus (884) Google Scholar) and rapidly adopted by the community. Yet, the array of posttranslational modifications is and the of many that glycoproteomics to on a a include R.C. B. intact glycopeptide identification by database 2018; PubMed Scopus Google R. W. M. M. Larsen M.R. in 2018; PubMed Scopus Google Scholar) or M.S. J.J. with 10: PubMed Scopus Google Scholar) These on proteomics to as protein identification by searching PubMed Scopus Google Scholar) and Baker of a database to glycopeptide identification from Chem. PubMed Scopus Google Scholar) or glycoproteomics in as in H. J. and glycoproteomics and PubMed Scopus Google Scholar). 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Zhang H. T. S. R. M. A. E. S. T. Y. B. R. R. H. S. A. R. P.M. R. E.S. J. P. A. C. S. S. J. T. S. A. S. M. P. C. P. Y. S. R. M. C. C. B. A. M. C. B. C. J. J. B. A. E. H. E. S. A. Y. R. W. H. S. E. study on of of results from PubMed Scopus Google Scholar) and the of the in and in and to in the file that be another is a that the of the To on the of is in the comparative of of the in and in and in is a on the with The in associated with is with the of and are in the of the from is is is in the GlyConnect database in D.R. B. of from and PubMed Scopus Google Scholar). These the of closely a to the of We a tool to and data based on the of a single of glycan the tool and can Compozitor a of through interactive To it offers a on the content of the GlyConnect database and the of at the of a a a or a it the of a composition file to a search in a The content of file can be from with and the of the GlyConnect database. The is the of data. The Compozitor interface was to in that the of a the of associated the of a glycan a of be it be to and the with the of the As as part of the [email protected] initiative, also to the tool from of

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