pepsickle rapidly and accurately predicts proteasomal cleavage sites for improved neoantigen identification.

MOTIVATION: Proteasomal cleavage is a key component in protein turnover, as well as antigen processing and presentation. Although tools for proteasomal cleavage prediction are available, they vary widely in their performance, options and availability. RESULTS: Herein, we present pepsickle, an open-source tool for proteasomal cleavage prediction with better in vivo prediction performance (area under the curve) and computational speed than current models available in the field and with the ability to predict sites based on both constitutive and immunoproteasome profiles. Post hoc filtering of predicted patient neoepitopes using pepsickle significantly enriches for immune-responsive epitopes and may improve current epitope prediction and vaccine development pipelines. AVAILABILITY AND IMPLEMENTATION: pepsickle is open source and available at https://github.com/pdxgx/pepsickle. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Responses to Song Playback Differ in Sleeping versus Anesthetized Songbirds.

Vocal learning in songbirds is mediated by a highly localized system of interconnected forebrain regions, including recurrent loops that traverse the cortex, basal ganglia, and thalamus. This brain-behavior system provides a powerful model for elucidating mechanisms of vocal learning, with implications for learning speech in human infants, as well as for advancing our understanding of skill learning in general. A long history of experiments in this area has tested neural responses to playback of different song stimuli in anesthetized birds at different stages of vocal development. These studies have demonstrated selectivity for different song types that provide neural signatures of learning. In contrast to the ease of obtaining responses to song playback in anesthetized birds, song-evoked responses in awake birds are greatly reduced or absent, indicating that behavioral state is an important determinant of neural responsivity. Song-evoked responses can be elicited during sleep as well as anesthesia, and the selectivity of responses to song playback in adult birds is highly similar between anesthetized and sleeping states, encouraging the idea that anesthesia and sleep are similar. In contrast to that idea, we report evidence that cortical responses to song playback in juvenile zebra finches (Taeniopygia guttata) differ greatly between sleep and urethane anesthesia. This finding indicates that behavioral states differ in sleep versus anesthesia and raises questions about relationships between developmental changes in sleep activity, selectivity for different song types, and the neural substrate for vocal learning.