TDEaseNexus: A Traceable, Open-Source AI Agent Platform for Top-Down Proteomics Data Analysis

Top-down proteomics (TDP) data analysis methods are continually evolving to extract increasingly comprehensive information from the highly complex datasets. However, researchers often need to coordinate multiple processing tools, write custom scripts, and rely on expert knowledge to fully interpret experimental results. To streamline the workflows and lower technical barriers, we present TDEaseNexus, an open-source desktop platform that unifies workflow execution, proteoform characterization, and interactive visualization through a natural-language AI agent. Through its AI-native interface and modular structure, researchers can execute adaptable TDP pipelines and perform label-free quantification, post-translational modification characterization, and positional-isomer quantification by stating their analytical goals. Domain-specific Skills and a Rust-based mass spectrometry toolkit provide deterministic calculations for modification searches, precursor-mass calibration, and spectral evidence analysis. The resulting analytical outputs can be inspected through interactive visualizations, while all analysis steps are automatically recorded for data provenance. As an open-source platform distributed with its complete analytical stack (https://github.com/Computational-TDMS/TDEaseNexus), TDEaseNexus facilitates routine TDP data interpretation and record-keeping, with the potential to broaden access to the development of new computational TDP methods.