NMSA conference, Malaga 2017 - Penny Nymark
Channel: Penny Nymark
Date: 2021-12-08

Presentation by Penny Nymark at the New tools and approaches for nanomaterial safety assessment conference (NMSA). This work was published in the journal Toxicological Sciences in 2018: https://doi.org/10.1093/toxsci/kfx252 

A PATHWAY TOOL FOR APPLYING “BIG DATA” IN NANOSAFETY-FOCUSED READ ACROSS AND ADVERSE OUTCOME STUDIES
Penny Nymark1,2, Linda Rieswijk3, Friederike Ehrhart3, Pekka Kohonen1,2, Vesa Hongisto2, Nina Jeliazkova4, Georgia Tsiliki5, Haralambos Sarimveis5, Chris Evelo3, Egon Willighagen3, Roland Grafström1,2

1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
2 Department of Toxicology, Misvik Biology, Turku, Finland
3 Department of Bioinformatics, Maastricht University, Maastricht, the Netherlands
4 IdeaConsult Ltd., Sofia, Bulgaria
5 School of Chemical Engineering, National Technical University of Athens, Athens, Greece

A focus of several ongoing European Nano Safety Cluster projects is to compress and interpret omics-generated results into useful predictive biological pathway-based analysis concepts and tools. We hypothesized that focused subsets of relevant curated adverse outcome-specific pathways may allow for deepened risk analysis. Using the open collaborative pathway platform WikiPathways, we created an ENM portal enabling community-based annotation of toxicity pathways and adverse outcomes relevant to nanosafety (http://www.wikipathways.org/index.php/Portal:Nanomaterials). Pulmonary fibrosis, a serious chronic respiratory condition induced by a wide variety of environmental and occupational exposures such as asbestos, silica dust and potentially also multi-walled carbon nanotubes, was selected to test the concept. Information and data related to lung fibrosis and ENMs were extracted and mined from public data sources. Using the bioinformatics tool PathVisio, the following steps generated a first description of a bioinformatically employable WikiPathway for this adverse outcome: a general scheme for the molecular processes of lung fibrosis was drawn based on selected review articles; sixty-four lung fibrosis associated genes with direct association were obtained from the Comparative Toxicogenomics Database; interactions between the 64 genes were obtained from the GeneMANIA database; highly interactive groups of genes were analysed for pathway or gene ontology enrichment using the Consensus Pathway Database; and finally, the elements of the pathway were linked to key events in two recently published putative adverse outcome pathways (AOPs) for pulmonary fibrosis. Transcriptomics data from pulmonary fibrosis patients and human cells exposed in vitro to various agents, including diverse ENM, but also fibrosis-associated chemicals and particles, was analysed and visualized using the novel WikiPathway. Overall, this workflow applied and compressed data from three lung fibrosis pathway-focused publications relative the three selected databases. We conclude based on these initial analyses that this novel workflow concept serves diversely for: i) gene set enrichment analysis, ii) pathway enrichment analysis among differentially expressed genes, iii) integration into AOP-based testing strategies, iv) application as descriptors in (Q)SAR approaches, and finally, iv) for grouping and read across among ENMs, coupled to identification of specific pathway-activating ENMs. Our further work aims to demonstrate the translational use of the novel tool generating concept for ENM safety assessment.

The NMSA conference was jointly organized by five major European FP7 projects NANOSOLUTIONS, GUIDEnano, SUN, NanoMILE and eNanoMapper, the conference aimed at presenting the main results achieved in the course of the projects fostering a discussion about their impact in the nanosafety field and possibilities for future research programmes.