Paper

Spatio-Temporal Multi-Omics Profiling of Mechanisms and Biomarkers in Inhaled Drug-Induced Lung Toxicity

Lindgren, Julia, Borde, Annika, Hamm, Gregory, Franzén, Lovisa, Costyson, Amanda, Di Poto, Cristina, Miele, Eric, Oag, Steve, Iannetta, Anthony A, Keith, Benjamin P, Azim, Adnan, Prasse, Antje, Johansson, Julia, Williams, Eleanor C, Ostridge, Kristoffer, Allman, Erik L, Jarnuczak, Andrew, Touza, Julia Liz, Terrillon, Sonia, Sand, Elin, Anderberg, Rozita H, Jones, Stewart, Lindvall, Martina Olsson, Majumder, Muntasir Mamun, Fitzpatrick, Paul, Ollerstam, Anna, Hornberg, Jorrit J, Ståhl, Patrik L, Mohorianu, Irina, Chen, Jeff, Tan, Jennifer, Hess, Sonja, Setyo, Laura, Corkill, Dominic, Åberg, Per

2025

Overview

Comprehensive understanding and early detection of drug-induced lung toxicity remain critical challenges in respiratory drug development. In this study, we propose a multi-omics framework that integrates spatial and temporal tissue-specific transcriptomic signatures with proteomics from minimally invasive biofluids to understand mechanisms and identify safety biomarkers associated with lung toxicity. Using this framework, we identified a panel of candidate biomarkers in bronchoalveolar lavage fluid and plasma, including LCN2/NGAL, RETNLA, SP-D, SPP1/osteopontin, and MMP7, that correlate with histopathological features (e.g., inflammation and epithelial remodeling). We confirmed that these molecular biomarkers were consistently dysregulated across a range of inhaled lung toxicants, human disease (IPF), and environmental exposures (smoke, Alternaria), demonstrating broad applicability across different toxic exposures and translatability. Collectively, this study establishes a robust workflow for mechanism-guided biomarker discovery and proposes a panel of candidates for monitoring drug-induced lung injury in humans.

• Publisher: Cold Spring Harbor Laboratory
• Subject: Systems Biology