Project description:This data is a re-analysis of samples used in a prior study (doi:10.1371/journal.pone.0123295) evaluating plasma candidate biomarkers of chronic domoic acid toxicosis (DAT) in California sea lions (Zalophus californianus). The previous study used 2D-gel electrophoresis to analyze plasma from a training (n = 32; 12 DAT and 20 non-DAT) and validation set (n = 20; 7 DAT and 13 non-DAT). Using spot intensity followed by in-gel digestion and LC-MS/MS, decreased ApoE was identified and qualified as a classifier of chronic DAT. The current analysis is from 31 of these samples (14 DAT and 17 non-DAT), since some samples were no longer available or had been through too many freeze/thaw cycles and were no longer suitable for robust analysis. This subset of 31 undepleted plasma samples was analyzed using shotgun proteomics with a tribrid mass spectrometer, and searching was performed with the recently completed California sea lion genome (https://www.ncbi.nlm.nih.gov/genome/annotation_euk/Zalophus_californianus/100/). Using MS1-based label-free methods we were able to identify candidate markers of chronic DAT, such as decreasing ApoE, ApoC-III and ApoB-100. We expect other analytical pipelines could be used to analyze this data, and we deliberately collected the MS1 and MS2 at high resolution to enable spectral library creation for approaches such as data-independent acquisition, which may be used in follow-up studies.
Project description:Since 1998, California sea lion stranding events associated with domoic acid toxicosis (DAT) have consistently increased and there are no practical non-lethal clinical tests for the diagnosis of domoic acid toxicosis that can be utilized in a large-scale rehabilitation facility. Proteomic analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid (CSF) from stranded sea lions with acute DAT, chronic DAT, or without DAT. A total of 2005 protein families were identified across 40 CSF samples (FDR<0.01) using the annotated California sea lion genome. Of these proteins, 83 were significantly different in abundance across the three groups (p<0.05). Comparisons between all sea lions with DAT versus those without DAT indicated that 119 proteins were significantly different between both groups (p<0.05); whereas, 47 proteins were significantly different between acute DAT and chronic DAT (p<0.05). Significant proteins were assessed as classifiers using ROC curves. Compared to sea lions with non-DAT, those with either acute or chronic DAT displayed higher levels of 14-3-3 proteins and malate dehydrogenase, and lower levels of 5’-3’ exonuclease PLD3, neurosecretory protein VGF, disintegrin and metalloproteinase domain-containing protein, and calsyntenin-1. When comparing acute DAT versus chronic DAT, 4 proteins were identified as good classifiers. Elevated levels of beta-synuclein was detected in acute DAT, and was identified as a high classifier for both comparisons. Many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions, as well as markers to discriminate between acute or chronic DAT, and should be considered priority for future validation studies as biomarkers.
