[
International Worm Meeting,
2021]
Neuropeptides are a class of bioactive peptides that obtain their biological activity after cleavage from larger precursor proteins. Once released, these peptides are able to regulate standard physiological functions such as digestion and reproduction but also exert long-term effects in more complex processes, including behavioral adaptation, memory processes and aging. Hence, neuropeptides are often an interesting entry point in an effort to study and better understand these types of behavior. Current strategies for studying relative differences in the neuropeptidome often rely on RNA sequencing, which remains completely blind to the real abundancies of actual neuropeptides, as these result from extensive post-translational processing. On the other hand, current mass spectrometric methods for neuropeptide identification are discovery-driven and lack robustness and reproducibility, hampering quantitative studies. We here present a mass spectrometry-based approach for the relative quantification of the neuropeptidome in C. elegans, using a parallel reaction monitoring method. Our current method can detect and quantify 288 mature neuropeptides, this corresponds to 67% of the (known and predicted) neuropeptidome of C. elegans. When applied to wild type controls, our method identified 178 neuropeptides with a 96% overlap between samples. Insofar as we are aware, we hereby are able to provide the most extensive method to map the peptidome of an animal. We are validating the method for differential studies, delivering a promising avenue to finally enable the detection and differential analysis of neuropeptidomic variations over different conditions.