Distinguishing and Biochemical Phenotype Analysis of Epilepsy Patients Using a Novel Serum Profiling Platform

Abstract

Diagnosis of non-symptomatic epilepsy includes a history of two or more seizures and brain imaging to rule out structural changes like trauma, tumor, infection. Such analysis can be problematic. It is important to develop capabilities to help identify non-symptomatic epilepsy in order to better monitor and understand the condition. This understanding could lead to improved diagnostics and therapeutics. Serum mass peak profiling was performed using electrospray ionization mass spectrometry (ESI-MS). A comparison of sera mass peaks between epilepsy and control groups was performed via leave one [serum sample] out cross-validation (LOOCV). MS/MS peptide analysis was performed on serum mass peaks to compare epilepsy patient and control groups. LOOCV identified significant differences between the epilepsy patient group and control group (p = 10−22). This value became non-significant (p = 0.10) when the samples were randomly allocated between the groups and reanalyzed by LOOCV. LOOCV was thus able to distinguish a non-symptomatic epilepsy patient group from a control group based on physiological differences and underlying phenotype. MS/MS was able to identify potential peptide/protein changes involved in this epilepsy versus control comparison, with 70% of the top 100 proteins indicating overall neurologic function. Specifically, peptide/protein sera changes suggested neuro-inflammatory, seizure, ion-channel, synapse, and autoimmune pathways changing between epilepsy patients and controls.

Keywords

• epilepsy
• monitoring
• serum profiling
• phenotype analysis
• mass spectrometry