Nicholas Bostic | 2026 I.S. Symposium
Name: Nicholas Bostic
Title: Potential Biomarker Discovery for Dilated Cardiomyopathy in Patients with Propionic Acidemia Using a Targeted Approach from Cardiovascular Literature
Major: Biochemistry and Molecular Biology
Minor: Religious Studies
Advisor: Paul Edmiston
Propionic acidemia (PA) is a rare inherited metabolic disorder caused by reduced activity of propionyl-CoA carboxylase (PCC), leading to an accumulation of metabolic intermediates. The PA missense variant in the PCCB gene (c.1606A>G; p.Asn536Asp), a common mutation in the Amish population and is associated with the development of dilated cardiomyopathy (DCM), a condition characterized by ventricular dilation and impaired ejection fraction that can progress to heart failure. Early detection of DCM in PA patients remains difficult because reliable biomarkers have not yet been established. This study aimed to find potential blood serum potential biomarkers for DCM in PA patients using a targeted suspect screening, developed from a comprehensive library of other metabolomic studies. A cardio-literature suspect list (CSL) comprising of 241 suspects was developed from cardiovascular linked metabolomics. The CSL was screened against 86 serum blood samples from Amish patients with PA (77 serum samples) and PA+ DCM (9 serum samples). Of the 241 suspects, 187 features were detected in the serum dataset and 138 features passed quality filtering for statistical analysis. 18 features showed statistical significance between the two cohorts. Nine potential biomarker identities were confirmed by matching their MS/MS spectra with a standards MS/MS spectra, including urate, homoarginine, gamma-glutamylleucine, N-acetyl-neuraminic acid, 3-methylglutaroylcarnitine, 3-methylhistidine, methylguanosine, succinate, and gamma-glutamylvaline. Additionally, nine other unidentified potential biomarkers were found to be significant. These results demonstrate that a literature-guided suspect screening approach can effectively identify potential biomarkers in metabolomics studies, using other metabolomic literature to guide the targeted approach.
Posted in Symposium 2026 on May 1, 2026.
