To enable our deep learning approach, we downloaded TDP data files from MassIVE and the Proteomics Data Exchange. Full details on the training data used are provided in the Supplemental Methods (SM1). Additional data files were downloaded to test the full workflow and were not included in either the training or testing of the neural network. For these workflow tests, we first selected three averaged MS2 spectra from top-down proteomics experiments: ultraviolet photodissociation (UVPD)-fragmented carbonic anhydrase II on an Orbitrap Fusion Lumos, electron-transfer dissociation (ETD)-fragmented carbonic anhydrase II on a 21 T FT-ICR, and electron-capture dissociation (ECD)-fragmented apomyoglobin on an Agilent 6560c Q-ToF. These spectra were selected to provide a rich dataset of top-down fragments that could be compared between instruments and fragmentation methods. Beyond these isolated spectra, we also selected a set of six replicate E. coli top-down LC-MS/MS injections to assess speed, reproducibility, and performance of IsoDec in the context of a top-down proteomics database search with data with multiple mixed MS1 and MS2 scans.