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Abstract
There is an urgent need to apply effective, data-driven approaches to reliably predict engineered nanomaterial (ENM) toxicity. Here we introduce a predictive computational framework based on the molecular and phenotypic effects of a large panel of ENMs across multiple in vitro and in vivo models. Our methodology allows for the grouping of ENMs based on multi-omics approaches combined with robust toxicity tests. Importantly, we identify mRNA-based toxicity markers and extensively replicate them in multiple independent datasets. We find that models based on combinations of omics-derived features and material intrinsic properties display significantly improved predictive accuracy as compared to physicochemical properties alone.
Nanomaterials have a range of potential applications, however, toxicity remains a concern, limiting application and requiring extensive testing. Here, the authors report on a predictive framework made using a range of tests linking materials properties with toxicity, allowing the prediction of toxicity from physiochemical and biological properties.
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1 University of Eastern Finland, Institute of Biomedicine, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490)
2 Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254); Tampere University, BioMediTech Institute, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254); University of Helsinki, Institute of Biotechnology, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland (GRID:grid.7737.4)
3 Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254); Tampere University, BioMediTech Institute, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254); Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere, Finland (GRID:grid.502801.e)
4 Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
5 Finnish Institute of Occupational Health, Helsinki, Finland (GRID:grid.6975.d) (ISNI:0000 0004 0410 5926)
6 Technical University of Denmark, National Food Institute, Kgs. Lynby, Denmark (GRID:grid.5170.3) (ISNI:0000 0001 2181 8870)
7 University of Turku, and Åbo Akademi University, Turku Bioscience Centre, Turku, Finland (GRID:grid.452861.c) (ISNI:0000 0004 0542 0522)
8 Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
9 Royal College of Surgeons in Ireland, Department of Pharmaceutical and Medicinal Chemistry, Dublin, Ireland (GRID:grid.4912.e) (ISNI:0000 0004 0488 7120)
10 Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626)
11 Institute of Occupational Medicine, Edinburgh, UK (GRID:grid.410343.1) (ISNI:0000 0001 2224 0230)
12 CIC biomaGUNE, Soft Matter Nanotechnology Laboratory, San Sebastian, Spain (GRID:grid.424269.f) (ISNI:0000 0004 1808 1283)
13 Leitat Technological Center, Terrassa, Spain (GRID:grid.452632.4) (ISNI:0000 0004 1762 4290)
14 University of Plymouth, School of Biological and Marine Sciences, Plymouth, UK (GRID:grid.11201.33) (ISNI:0000 0001 2219 0747)
15 Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Division of Toxicology, Misvik Biology, Turku, Finland (GRID:grid.4714.6)
16 University College Dublin, Centre for BioNano Interactions, School of Chemistry and Chemical Biology, Dublin, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743)
17 Ludwig-Maximilians-Universität München, Walter Brendel Centre of Experimental Medicine, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X)
18 Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of Helsinki, Department of Bacteriology and Immunology, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)