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.

Details

Title
Biomarkers of nanomaterials hazard from multi-layer data
Author
Fortino, Vittorio 1   VIAFID ORCID Logo  ; Kinaret, Pia Anneli Sofia 2 ; Fratello, Michele 3   VIAFID ORCID Logo  ; Serra, Angela 3   VIAFID ORCID Logo  ; Saarimäki, Laura Aliisa 3 ; Gallud, Audrey 4 ; Gupta, Govind 4 ; Vales, Gerard 5 ; Correia, Manuel 6 ; Rasool, Omid 7 ; Ytterberg, Jimmy 8 ; Monopoli, Marco 9 ; Skoog, Tiina 10   VIAFID ORCID Logo  ; Ritchie, Peter 11 ; Moya, Sergio 12 ; Vázquez-Campos, Socorro 13 ; Handy, Richard 14 ; Grafström, Roland 15 ; Tran, Lang 11 ; Zubarev, Roman 8   VIAFID ORCID Logo  ; Lahesmaa, Riitta 7 ; Dawson, Kenneth 16   VIAFID ORCID Logo  ; Loeschner, Katrin 6   VIAFID ORCID Logo  ; Larsen, Erik Husfeldt 6 ; Krombach, Fritz 17 ; Norppa, Hannu 5 ; Kere, Juha 10   VIAFID ORCID Logo  ; Savolainen, Kai 5 ; Alenius, Harri 18   VIAFID ORCID Logo  ; Fadeel, Bengt 4   VIAFID ORCID Logo  ; Greco, Dario 2   VIAFID ORCID Logo 

 University of Eastern Finland, Institute of Biomedicine, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490) 
 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) 
 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) 
 Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
 Finnish Institute of Occupational Health, Helsinki, Finland (GRID:grid.6975.d) (ISNI:0000 0004 0410 5926) 
 Technical University of Denmark, National Food Institute, Kgs. Lynby, Denmark (GRID:grid.5170.3) (ISNI:0000 0001 2181 8870) 
 University of Turku, and Åbo Akademi University, Turku Bioscience Centre, Turku, Finland (GRID:grid.452861.c) (ISNI:0000 0004 0542 0522) 
 Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
 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) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2683055639
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.