A deep-learning framework reveals whole-body perturbations at cell level
Abstract
Abstract Many diseases, including obesity, have systemic effects that perturb multiple organ systems throughout the body 1,2 . However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking. Here we developed MouseMapper, a suite of foundation-model-based deep-learning algorithms enabling multi-system analysis of disease across the entire mouse body. MouseMapper enables whole-body quantitative analysis of nerves and immune cells, resolving fine axonal branches and immune-cell clusters while automatically segmenting 31 organs and tissues. We used MouseMapper to study diet-induced obesity, and identified structural alterations of the infraorbital branch of the trigeminal ganglia. This structural impairment in infraorbital nerves was associated with functional sensory deficits in whisker sensing. Furthermore, we identified proteomic changes in the trigeminal ganglion affecting axon remodelling and complement pathways both in mice and humans. MouseMapper also generated detailed three-dimensional inflammation maps by characterizing immune cell cluster compositions across tissues. The MouseMapper framework demonstrates robust generalizability across different imaging resolutions and datasets. Our study provides a powerful, scalable approach for identifying and quantifying systemic pathologies, bridging molecular insights from animal models to human conditions.
Article Details
Authors (41)
Doris Kaltenecker
Izabela Horvath
Rami Al-Maskari
Ying Chen
Zeynep Ilgin Kolabas
Luciano Hoeher
Mihail Todorov
David-Paul Minde
Saketh Kapoor
Sena Gül Turhan
Louis B. Kuemmerle
Hanno Steinke
Tim Wohlgemuth
Mayar Ali
Florian Kofler
Pauline Morigny
Julia Geppert
Denise Jeridi
Bastian Wittmann
Jie Luo
Suprosanna Shit
Carolina Cigankova
Victor Miro Kolenic
Nilsu Gür
Eren Aydeniz
Alara Yücecan
Melissa Ertürk
Laurent H. A. Simons
Chenchen Pan
Marie Piraud
Daniel Rueckert
Maria Rohm
Farida Hellal
Markus Elsner
Harsharan Singh Bhatia
Ingo Bechmann
Bjoern H. Menze
Stephan Herzig
Johannes Christian Paetzold
Mauricio Berriel Diaz
Ali Ertürk