Universiteitssingel 40, 6229 ER Maastricht
Prof. J.C.S. Kleinjans
0031 (0)43 3881096
The Netherlands Toxicogenomics Centre (NTC), led by Prof. J.C.S. Kleinjans of the Department of Toxicogenomics at Maastricht University, has been initiated by the Netherlands Genomics Initiative with the particular purpose to integrate ‘omics technologies. This integration occurs at two levels:
- NTC applies the full breath of “wet bench” ‘omics technologies, covering analyses of whole genome gene expression, microRNA regulation and epigenomics by applying microarray technologies and next generation sequencing methods, of proteomics by means of mass spectrometry, of metabolomics by means of NMR and mass spectrometry, and of functional genomics by means of life cell imaging, in order to utilize read-outs from multiple ‘omics platforms for achieving a better and in depth understanding of molecular mechanisms underlying toxic modes-of action
- NTC applies a wide range of ‘dry bench” technologies comprising bioinformatics, biostatistical and visualisation techniques, to achieve the actual integration of data delivered by multiple ‘omics platforms
NTC aims at integrating multiple ‘omics technologies for the purpose of applying obtained mechanistic insight to developing non-animal-based cellular models for better predicting human toxicity, in particular chemical carcinogenesis, immunotoxicity, reproduction toxicity, neurotoxicity, intestinal toxicity and livertoxicity, thereby replacing current animal models for assessing chemical safety.
For more information: http://www.toxicogenomics.nl/Home
- Biomedical & health
- NTC covers both fields of life sciences technology expertise, with probably a dominant role for experimental technologies
- In addition, to its multi-omics technologies, NTC may offer electron spin resonance techniques
- Genetic toxicology
- Reproduction toxicology
- Hepatic and renal toxicology
Expertise and Track Record
All hardware, software and experience necessary for performing and analyzing large-scale genomics studies is available. The team of Prof. J.C.S. Kleinjans was one of the first to report on RNA-seq analysis in toxicology. Currently, ~3650 samples have been sequenced and analyzed. In the coming 3 years it is expected that this number will grow above 5650 samples.
EU-ToxRisk (http://www.eu-toxrisk.eu/) – An Integrated European ‘Flagship’ Programme Driving Mechanism-based Toxicity Testing and Risk Assessment for the 21st century – is a European collaborative project funded by the EU Framework Programme for Research and Innovation, Horizon 2020. With a budget of over 30 million €, the project started on 1st January 2016 and will last for a duration of 6 years.
BReIN (Brightlands e-Infrastructure for Neurohealth) – A multi-omics/imaging project aiming at better understanding the impact of environmental factors on Alzheimer’s Disease. With a budget of over 20 million euro, the project started on 1st January 2019 and will last for a duration of 7 years.
NTC aims at integrating multiple ‘omics technologies
- Kuijpers TJM, Wolters JEJ, Kleinjans JCS, Jennen DGJ. DynOVis: a web tool to study dynamic perturbations for capturing dose-over-time effects in biological networks. BMC Bioinformatics. 2019 Aug 13;20(1):417. doi: 10.1186/s12859-019-2995-y.
- Hendrickx DM, Souza T, Jennen DGJ, Kleinjans JCS. DTNI: a novel toxicogenomics data analysis tool for identifying the molecular mechanisms underlying the adverse effects of toxic compounds. Arch Toxicol. 2017 Jun;91(6):2343-2352. doi: 10.1007/s00204-016-1922-5. Epub 2016 Dec 28.
- Wolters JEJ, van Breda SGJ, Grossmann J, Fortes C, Caiment F, Kleinjans JCS. Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13. doi: 10.1016/j.toxlet.2018.02.026. Epub 2018 Mar 6.
- Hebels DG, Rasche A, Herwig R, van Westen GJ, Jennen DG, Kleinjans JC. A Systems Biology Approach for Identifying Hepatotoxicant Groups Based on Similarity in Mechanisms of Action and Chemical Structure. Methods Mol Biol. 2016;1425:339-59. doi: 10.1007/978-1-4939-3609-0_15. PubMed PMID: 27311473.
- Rieswijk L, Brauers KJ, Coonen ML, Jennen DG, van Breda SG, Kleinjans JC. Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity. Mutagenesis. 2016 Sep;31(5):603-15. doi: 10.1093/mutage/gew027. Epub 2016 Jun 23. PubMed PMID: 27338304
- Cavill R, Jennen D, Kleinjans J, Briedé JJ. Transcriptomic and metabolomic data integration. Brief Bioinform. 2016 Sep;17(5):891-901. doi: 10.1093/bib/bbv090. Epub 2015 Oct 14. PubMed PMID: 26467821.
- Caiment F, Gaj S, Claessen S, Kleinjans J. High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity. Nucleic Acids Res. 2015 Mar 11;43(5):2525-34. doi: 10.1093/nar/gkv115. Epub 2015 Feb 17.
- Van den Hof WF, Ruiz-Aracama A, Van Summeren A, Jennen DG, Gaj S, Coonen ML, Brauers K, Wodzig WK, van Delft JH, Kleinjans JC. Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501. doi: 10.1016/j.tiv.2014.12.016. Epub 2015 Jan 3. PubMed PMID: 25562108.
- Jennen DG, van Leeuwen DM, Hendrickx DM, Gottschalk RW, van Delft JH, Kleinjans JC. Bayesian Network Inference Enables Unbiased Phenotypic Anchoring of Transcriptomic Responses to Cigarette Smoke in Humans. Chem Res Toxicol. 2015 Oct 19;28(10):1936-48. doi: 10.1021/acs.chemrestox.5b00145. Epub 2015 Sep 17. PubMed PMID: 26360787.
- SEQC/MAQC-III Consortium. A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium. Nat Biotechnol. 2014 Sep;32(9):903-14. doi: 10.1038/nbt.2957. Epub 2014 Aug 24. PubMed PMID: 25150838; PubMed Central PMCID: PMC4321899.
Netherlands Toxicogenomics Centre
- Illumina Novaseq 6000
- Illumina Miniseq system
- Illumina iSeq 100 system
- ESR system
The diXa data warehouse: http://wwwdev.ebi.ac.uk/fg/dixa/index.html; https://www.ebi.ac.uk/biostudies/diXa/studies