UniCarb-DB: An MS/MS Experimental Glycomic Fragmentation Database.

Glycosylation is a unique posttranslational modification that dynamically shapes the surface of cells. Glycans attached to proteins or lipids in a cell or tissue are studied as a whole and collectively designated as a glycome. UniCarb-DB is a glycomic spectral library of tandem mass spectrometry (MS/MS) fragment data. The current version of the database consists of over 1500 entries and over 1000 unique structures. Each entry contains parent ion information with associated MS/MS spectra, metadata about the original publication, experimental conditions, and biological origin. Each structure is also associated with the GlyTouCan glycan structure repository allowing easy access to other glycomic resources. The database can be directly utilized by mass spectrometry (MS) experimentalists through the conversion of data generated by MS into structural information. Flexible online search tools along with a downloadable version of the database are easily incorporated in either commercial or open-access MS software. This chapter highlights UniCarb-DB online search tool to browse differences of isomeric structures between spectra, a peak matching search between user-generated MS/MS spectra and spectra stored in UniCarb-DB and more advanced MS tools for combined quantitative and qualitative glycomics.

The international glycan repository GlyTouCan version 3.0.

Glycans serve important roles in signaling events and cell-cell communication, and they are recognized by lectins, viruses and bacteria, playing a variety of roles in many biological processes. However, there was no system to organize the plethora of glycan-related data in the literature. Thus GlyTouCan (https://glytoucan.org) was developed as the international glycan repository, allowing researchers to assign accession numbers to glycans. This also aided in the integration of glycan data across various databases. GlyTouCan assigns accession numbers to glycans which are defined as sets of monosaccharides, which may or may not be characterized with linkage information. GlyTouCan was developed to be able to recognize any level of ambiguity in glycans and uniquely assign accession numbers to each of them, regardless of the input text format. In this manuscript, we describe the latest update to GlyTouCan in version 3.0, its usage, and plans for future development.

BioHackathon 2015: Semantics of data for life sciences and reproducible research.

We report on the activities of the 2015 edition of the BioHackathon, an annual event that brings together researchers and developers from around the world to develop tools and technologies that promote the reusability of biological data. We discuss issues surrounding the representation, publication, integration, mining and reuse of biological data and metadata across a wide range of biomedical data types of relevance for the life sciences, including chemistry, genotypes and phenotypes, orthology and phylogeny, proteomics, genomics, glycomics, and metabolomics. We describe our progress to address ongoing challenges to the reusability and reproducibility of research results, and identify outstanding issues that continue to impede the progress of bioinformatics research. We share our perspective on the state of the art, continued challenges, and goals for future research and development for the life sciences Semantic Web.

Towards a standardized bioinformatics infrastructure for N- and O-glycomics.

The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N- and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.

GlyTouCan: an accessible glycan structure repository.

Rapid and continued growth in the generation of glycomic data has revealed the need for enhanced development of basic infrastructure for presenting and interpreting these datasets in a manner that engages the broader biomedical research community. Early in their growth, the genomic and proteomic fields implemented mechanisms for assigning unique gene and protein identifiers that were essential for organizing data presentation and for enhancing bioinformatic approaches to extracting knowledge. Similar unique identifiers are currently absent from glycomic data. In order to facilitate continued growth and expanded accessibility of glycomic data, the authors strongly encourage the glycomics community to coordinate the submission of their glycan structures to the GlyTouCan Repository and to make use of GlyTouCan identifiers in their communications and publications. The authors also deeply encourage journals to recommend a submission workflow in which submitted publications utilize GlyTouCan identifiers as a standard reference for explicitly describing glycan structures cited in manuscripts.

Implementation of GlycanBuilder to draw a wide variety of ambiguous glycans.

GlyTouCan version 1.0 was released in 2015 as the international glycan structure repository, and a new sequence format called WURCS (Web3 Unique Representation of Carbohydrate Structures) was proposed during the early stages of the GlyTouCan project. GlyTouCan uses WURCS as its base representation for glycans because existing formats were insufficient in their flexibility to represent any and all glycans universally. Therefore, in order to obtain WURCS strings for existing or new glycan structures, conversion tools or glycan structure editors that can export WURCS became necessary. GlycanBuilder was an obvious choice to extend due to its wide usage by the community. However, GlycanBuilder was limited because it was originally developed to support mammalian glycans. It also did not support the newly proposed monosaccharide symbol standard called Symbol Nomenclature for Glycans (SNFG). Therefore in this work, we implemented a new version of GlycanBuilder to greatly increase its usability. The glycan rendering system was refactored so that cyclic glycans, nested repeating units, monosaccharide compositions and cross-linked glycan structures can be represented. Both import and export utilities for WURCS were also implemented and SNFG symbols were incorporated to allow glycans to be exported as graphics using the latest glycan symbol nomenclature. This new version of GlycanBuilder called "GlycanBuilder2", is able to support a wide variety of ambiguous glycans, including structures containing monosaccharides from bacteria and plants. These glycans can also be displayed using the new SNFG symbols. This tool can aid researchers in communicating about the complex, diverse, and ambiguous structures of glycans more rapidly. Moreover, the new GlycanBuilder can now easily output WURCS sequences from glycans drawn on the canvas. Most importantly, because GlyTouCan employs WURCS as the basic format for registration and searching of glycan information, a wider variety of glycans can now be readily registered and queried in GlyTouCan.

WURCS 2.0 Update To Encapsulate Ambiguous Carbohydrate Structures.

Accurate representation of structural ambiguity is important for storing carbohydrate structures containing varying levels of ambiguity in the literature and databases. Although many representations for carbohydrates have been developed in the past, a generalized but discrete representation format did not exist. We had previously developed the Web3 Unique Representation of Carbohydrate Structures (WURCS) in an attempt to define a generalizable and unique linear representation for carbohydrate structures. However, it lacked sufficient rules to uniquely describe ambiguous structures. In this work, we updated WURCS to handle such ambiguous monosaccharide structures. In particular, to handle structural ambiguity around (potential) carbonyl groups incidental to the carbohydrate analysis, we defined a representation of backbone carbons containing atomic-level ambiguity. As a result, we show that WURCS 2.0 can represent a wider variety of carbohydrate structures containing ambiguous monosaccharides, such as those whose ring closure is undefined or whose anomeric information is only known. This new format provides a representation of carbohydrates that was not possible before, and it is currently being used by the International Glycan Structure Repository GlyTouCan.

GlyTouCan 1.0--The international glycan structure repository.

Glycans are known as the third major class of biopolymers, next to DNA and proteins. They cover the surfaces of many cells, serving as the 'face' of cells, whereby other biomolecules and viruses interact. The structure of glycans, however, differs greatly from DNA and proteins in that they are branched, as opposed to linear sequences of amino acids or nucleotides. Therefore, the storage of glycan information in databases, let alone their curation, has been a difficult problem. This has caused many duplicated efforts when integration is attempted between different databases, making an international repository for glycan structures, where unique accession numbers are assigned to every identified glycan structure, necessary. As such, an international team of developers and glycobiologists have collaborated to develop this repository, called GlyTouCan and is available at http://glytoucan.org/, to provide a centralized resource for depositing glycan structures, compositions and topologies, and to retrieve accession numbers for each of these registered entries. This will thus enable researchers to reference glycan structures simply by accession number, as opposed to by chemical structure, which has been a burden to integrate glycomics databases in the past.