Title: Integrative Multiomics Profiling of Glycosylation and Metabolic Alterations in Severe Traumatic Brain Injury: Biomarker Discovery and Clinical Implications
Abstract:
Traumatic brain injury (TBI) presents significant global health challenges, with limited diagnostic and prognostic tools to monitor progression and inform clinical interventions. Emerging evidence highlights the crucial role of glycosylation and extracellular vesicle (EV)-mediated metabolic processes in TBI pathology. Here, we present a comprehensive, integrative multiomics analysis, employing advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, to profile glycomic and metabolomic alterations following severe TBI (sTBI).
We investigated dynamic changes in immunoglobulin G (IgG) and non-IgG N-glycosylation patterns in patient serum, identifying significant post-injury alterations, including increased sialylation and decreased bisection, galactosylation, and fucosylation at days 1, 3, and 5 post-injury. These glycan signatures suggest an active role in modulating immune responses post-TBI, potentially as prognostic biomarkers. Complementarily, we explored serum O-glycome changes, uncovering a pronounced abundance of Core 1 O-glycans (T antigen) and sialyl-T antigen—glycan species implicated in inflammatory responses and previously linked to disease progression, immune evasion, and blood-brain barrier compromise.
Additionally, leveraging optimized methodologies for small extracellular vesicle (sEV) isolation from patient serum and cerebrospinal fluid (CSF), we conducted comprehensive metabolic and glycomic profiling of sEVs. Metabolomic analyses revealed significant disruptions in glucose metabolism, amino acid synthesis, nucleotide pathways, and neurotransmitter metabolism within sEVs, reflecting systemic metabolic responses and injury severity. Glycomic profiling of sEV-derived N-glycans revealed a progressive reduction in sialylation over time in serum and CSF, highlighting potential markers correlating with injury progression and central nervous system pathology.
Collectively, these integrated glycomic and metabolomic insights underscore the critical importance of glycans and sEV-derived metabolites as powerful, noninvasive biomarkers capable of refining TBI diagnostics, prognostics, and therapeutic interventions. This multidimensional approach provides a novel framework applicable to TBI and broader neuroinflammatory and neurodegenerative disorders.
Bio:
Prof. Yehia Mechref is globally a distinguished figure in the field of biomolecular mass spectrometry at Texas Tech University, where he serves as the Robert A. Welch Endowed Chair in Chemistry, the Paul W. Horn Distinguished Professor, the Associate Vice President for Research and Innovation, and the Director of the Center for Biotechnology and Genomics. His groundbreaking work in analyzing proteins and glycans is revolutionizing the way diseases are diagnosed and treated globally. Prof. Mechref, who holds a B.Sc. from the American University of Beirut and a Ph.D. from Oklahoma State University, leads the Mechref Omics Lab. His leadership and extensive network of over 300 global collaborations emphasize his pivotal role in pushing the boundaries of scientific knowledge. With an impressive track record of 46 review articles, 26 book chapters, and 257 research papers, he is a prolific contributor to scientific literature, boasting an h-index of 74 on Google Scholar. His involvement in editorial duties, scientific committees, and the receipt of numerous awards for academic achievement and mentoring further affirm his significant impact and influence in the realms of chemistry, biochemistry, and cancer research internationally.
Keywords: mass spectrometry; Glycomics; Glycoproteomics; Metabolomics; TBI