Glycan Compositions with GlyConnect Compozitor to Enhance Glycopeptide Identification

Mariethoz, Julien; Hayes, Catherine A.; Lisacek, Frédérique

doi:10.1007/978-1-0716-1641-3_7

Cited by 5 publications

(7 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a test of the model, we considered the monosaccharide composition of HMOs as a crude grouping of structures. We entered the compositions of the sub-population defined above into GlyConnect Compozitor 78 , 79 , a tool that roughly simulates the incremental addition of monosaccharides from a nucleotide sugar to an acceptor. The network of compositions is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

McDonald

Mariethoz

Davey

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

Human milk oligosaccharides (HMOs) form the third most abundant component of human milk and are known to convey several benefits to the neonate, including protection from viral and bacterial pathogens, training of the immune system, and influencing the gut microbiome. As HMO production during lactation is driven by enzymes that are common to other glycosylation processes, we adapted a model of mucin-type GalNAc-linked glycosylation enzymes to act on free lactose. We identified a subset of 11 enzyme activities that can account for 206 of 226 distinct HMOs isolated from human milk and constructed a biosynthetic reaction network that identifies 5 new core HMO structures. A comparison of monosaccharide compositions demonstrated that the model was able to discriminate between two possible groups of intermediates between major subnetworks, and to assign possible structures to several previously uncharacterised HMOs. The effect of enzyme knockouts is presented, identifying β-1,4-galactosyltransferase and β-1,3-N-acetylglucosaminyltransferase as key enzyme activities involved in the generation of the observed HMO glycosylation patterns. The model also provides a synthesis chassis for the most common HMOs found in lactating mothers.

show abstract

Section: Resultsmentioning

confidence: 99%

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

McDonald

Mariethoz

Davey

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a test of the model, we considered the monosaccharide composition of HMOs as a crude grouping of structures. We entered the compositions of the sub-population defined above into GlyConnect Compozitor [58,59], a tool that roughly simulates the incremental addition of monosaccharides from a nucleotide sugar to an acceptor. The network of compositions is shown in Fig.…”

Section: Hmo Compositions Vs Structuresmentioning

confidence: 99%

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

McDonald

Mariethoz

Davey

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Human milk oligosaccharides (HMOs) form the third most abundant component of human milk and are known to convey several benefits to the neonate, including protection from viral and bacterial pathogens, training of the immune system, and influencing the gut microbiome. As HMO production during lactation is driven by enzymes that are common to other glycosylation processes, we adapted a model of mucin-type GalNAc-linked glycosylation enzymes to act on free lactose. We identified a subset of 11 enzyme activities that can account for 206 of 226 distinct HMOs isolated from human milk, and constructed a biosynthetic reaction network that identifies 5 new core HMO structures. A comparison of monosaccharide compositions demonstrated that the model was able to discriminate between two possible groups of intermediates between major subnetworks, and to assign possible structures to several previously uncharacterised HMOs. The effect of enzyme knockouts is presented, identifying β-1,4-galactosyltransferase and β-1,3-N-acetylglucosaminyltransferase as key enzyme activities involved in the generation of the observed HMO glycosylation patterns. The model also provides a synthesis chassis for the most common HMOs found in lactating mothers.

show abstract

“…More specifically, a virtual node is added to a network when the continuity of a path is disrupted and only one step is missing. Precise definitions can be found in (Robin et al, 2020) and examples of use in (Mariethoz et al, 2021). The comparison of all the real nodes (compositions) in the GlyConnect database with all the virtual nodes generated in Compozitor graphs it is possible to distinguish:…”

Section: Virtual Nodesmentioning

confidence: 99%

What is a consistent glycan composition dataset?

2023

Self Cite

View full text Add to dashboard Cite

Introduction: One of the main challenges in bioinformatics has been and still is, the comparison of entities through the development of algorithms for similarity scoring and data clustering according to biologically relevant aspects. Glycoinformatics also faces this challenge, in particular regarding the automated comparison of protein and/or tissue glycomes, that remains a relatively uncharted territory.Methods: Low and high throughput experimental glycomic and glycoproteomic results were collected, revealing a bias toward N-linked glycomes. Then, N-glycomes were considered and represented as networks of related glycan compositions as opposed to lists of glycans. They were processed and compared through a java application generating graphs and another producing a similarity matrix based on graph content. Several scoring schemes (e.g., Jaccard index or cosine) were tested and evaluated using the Matthews Correlation Coefficient, in order to capture a meaningful protein and tissue N-glycome similarity.Results: Assuming that a glycome corresponds to a well-connected graph of glycan compositions, graph comparison has revealed gaps that can be interpreted as inconsistencies. The outcome of systematic graph comparison is both formal and practical. In principle, it is shown that the idiosyncrasy of current glycome data limits the definition of appropriate estimates for systematically comparing N-glycomes. Yet, several potentially interesting criteria could be identified in a series of use cases detailed in the study.Discussion: Differentially expressed glycomes are usually compared manually, but the resulting work tends to remain in publications due to the lack of dedicated tools. Even manually, cross-comparison is challenging mostly because different sets of features are used from one study to the other. The work presented here enables laying down guidelines for developing a software tool comparing glycomes based on appropriate definitions of similarity and suitable methods for its evaluation and implementation.

show abstract

Glycan Compositions with GlyConnect Compozitor to Enhance Glycopeptide Identification

Cited by 5 publications

References 52 publications

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

What is a consistent glycan composition dataset?

Contact Info

Product

Resources

About