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Quorum: glycopeptide discovery via mass spectrometry and spectral networking

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44GM125485-02A1
Agency Tracking Number: R44GM125485
Amount: $1,923,528.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 400
Solicitation Number: PA19-272
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-09-10
Award End Date (Contract End Date): 2022-07-31
Small Business Information
San Diego, CA 92109-5754
United States
DUNS: 031092123
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (619) 752-4821
Business Contact
Phone: (888) 416-9305
Research Institution

Glycosylation is a pervasive modification estimated to modify more than 50% of
human proteins and is a key component of host-pathogen interactions, adaptive and
innate immunity, and therapeutic development. Computational tools for glycoprotein
analysis make simplifying assumptions about possible glycan structures, limiting their
utility in many scenarios. This proposal aims to comprehensively characterize
glycoproteins, including novel and unexpected glycans, with Digital Proteomics’ Quorum
mass spectrometry data analysis software, and enable further glycoprotein
characterization through the development of antibodies targeting discovered
glycopeptides.The Quorum software builds on the spectral networking paradigm that posits that
structurally similar molecules produce similar mass spectra. In Quorum for glycopeptide
analysis, networked spectra represent different glycan structures on the same glycosite
of a protein. Similar to traditional approaches to glycopeptide identification, Quorum
matches glycopeptide spectra to a protein sequence database and glycan structure
database. Unlike traditional approaches, Quorum employs a rigorous false-discovery
rate calculation based on variant glycan structures in target-decoy analysis. In addition,
Quorum increases the identification rate of glycopeptides by propagating identifications
along edges in the network, enabling the discovery of glycan structures that are not in
the structure database and may be completely novel.Quorum will be benchmarked on glycoprotein standards, well-characterized
NIST monoclonal antibody reference material, and total IgG which will establish a
baseline for spectral network variant glycopeptide discovery. The Quorum software is
deployed to the cloud, as part of our extensible platform Quorum Cloud, where the
glycoprotein analysis is a plugin to generic spectral networking analysis. Enlisted testers
of the cloud platform have applications in glycoengineering, glycoenrichment assays,
and therapeutic development.Glycans are key modulators of protein stability and function, and play critical roles in
host-pathogen interactions, cancer metastasis, and immunology. Research into protein
glycosylation is hampered by inadequate tools to identify the full diversity of glycan structures on
a proteins. We are developing Quorum, a software tool to accurately characterize glycan
structures on proteins to provide important information for therapeutic and diagnostic

* Information listed above is at the time of submission. *

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