TDP-43 Degradome Foundation Atlas

This open-access repository presents the TDP-43 Degradome Foundation Atlas, a high-resolution, fully annotated dataset of proteolytic TDP-43 fragments with complete amino acid sequences and detailed biochemical metadata.TDP-43 is a central molecular driver of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), with cytoplasmic aggregation and C- and N-terminal fragmentation representing pathological hallmarks of disease. The Atlas captures TDP-43 as a dynamic ensemble of peptide fragments generated through physiological turnover, stress-related processing, and disease-associated cleavage. Version 1 includes the wild-type protein and can be expanded to selected disease-relevant variants. This provides a structured peptide-level framework for mechanistic and translational research on TDP-43.This dataset is suitable for classical biomarker discovery as well as for computational and AI-driven approaches in neurodegeneration. The structured, labelled format makes it particularly valuable for:Training supervised models to detect or predict proteolytic cleavage sitesFeature extraction from intrinsically disordered and RNA-binding protein sequencesModelling relationships between fragmentation, phase separation, and aggregationClustering fragment profiles by mutation or disease contextIntegrating with transcriptomic, proteomic, or immunological datasets for multimodal analysesDataset Features:Systematically enumerated and annotated TDP-43 proteolytic fragmentsDetailed biochemical and biophysical peptide descriptorsTab-delimited ASCII / CSV format compatible with Python, R, SAS, and ML frameworksFully reproducible Python workflow for regeneration and expansionDesigned for iterative updates as new TDP-43 mutations and cleavage sites are identifiedThe dataset was generated using a transparent, reproducible computational pipeline based on open-source tools. All scripts are provided and documented, enabling full reproducibility and adaptation to future research needs.This Atlas is particularly relevant for researchers in neurodegeneration, proteomics, RNA biology, bioinformatics, neuroinflammation, and artificial intelligence who are developing tools to understand, predict, and therapeutically target TDP-43 fragmentation and aggregation pathways in human disease.