# Exploring the sepsis-delirium connection through glycoproteomics

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $236,437

## Abstract

ABSTRACT
Our proposal seeks to create and apply new glycoproteomics procedures that permit unbiased discovery of
alterations in protein glycosylation. This includes the creation of algorithms that assemble glycoproteoform
networks from multi-dimensional mass spectrometry (MS) datasets, the prediction of underlying glycan
information directly from intact glycoprotein MS spectral information, and statistical scoring with unique
glycoproteoform informatics tools. An innovative aspect of the proposed technologies is that they are intended
to permit evaluation of glycoproteins and prediction of glycan level information when glycosylation occurs at more
than one amino acid residue, a well-recognized bottleneck in the top-down mass spectrometry field. Our aims
also include the application of the algorithms to enable unsupervised "discovery" of glycoproteoforms biomarkers
in biofluids. We will use these new tools to monitor the blood-plasma/serum of patients that derive from the
DECODE-Sepsis and BRAIN-ICU programs with the intent to discover glycoproteoforms that correlate with
specific endotypes or clinical symptoms across the spectrum of sepsis disorders, including prediction of long-
term cognitive dysfunction. In particular, we seek to establish unique datasets that can be used to inform upon
sepsis that is tied to different anatomical regions or tied to complex mechanisms involved in both sepsis
(endothelial dysfunction and inflammatory responses) and sepsis-adjacent (i.e. immunosuppression) events.
Sepsis is life-threatening, leading to organ dysfunction due to a dysregulated host response to infection and is
an important global health problem that kills 11 million people each year and disables millions more. In the
United States, the CDC reports that 87% of sepsis or the infection causing sepsis starts outside the hospital.
These metrics highlight the urgent need for resources that can rapidly detect and stratify stages and mechanisms
associated with individual patients. Our targeted informatics workflow will be able to compile large volumes of
patient data to provide meaningful insight into the non-template driven regulation of glycosylation caused by
specific gene expression, providing both novel sub-phenotype and endotype knowledge that is absent in classic
non-glycoproteomics discovery. If our project aims are successful, we will not only have developed innovative
tools for glycomics and glycoproteomics, but also established clinical proteomics procedures for the discovery
and development of glycoprotein-based biomarkers.

## Key facts

- **NIH application ID:** 10511841
- **Project number:** 1R21GM147847-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Steven Matthew Patrie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,437
- **Award type:** 1
- **Project period:** 2022-08-05 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511841

## Citation

> US National Institutes of Health, RePORTER application 10511841, Exploring the sepsis-delirium connection through glycoproteomics (1R21GM147847-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10511841. Licensed CC0.

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