Ee679b, Erasmus MC, Dr Molewaterplein 50, 3000CA Rotterdam
Dr. ir. W.F. van IJcken
0031 (0)10 7044454
This document describes the collective machinery and expertise of two large facilities at Erasmus MC, the Erasmus Center for Biomics and the Human Genotyping Facility that recently merged into a newly formed Facilitary Unit: the Rotterdam Genomics Core.
This mission of this new genomics core is to design and deliver reliable and innovative services to the Erasmus MC life science community and its collaborators. The facility develops Applications & Services for Fundamental Research, Clinical Research and Clinical Diagnostics using Next Generation Sequencing & Micro-Array technology. Our NGS pipelines cover genetic analyses such as genome & exome sequencing, mutation & variant analyses and epigenetic analyses including RNA sequencing & expression analyses, ChIP sequencing and Chromatin Conformation Capture sequencing & analyses. In addition, we store and distribute RNAi libraries (>200000 clones), provide imaging technology and high throughput DNA isolation.
The facility has provided services to >1000 different customers, both academic and commercial. Since 2007 we have developed multiple innovative applications for fundamental research, such as multiplexed ChIP sequencing, Chromatin Conformation Capture (3C) sequencing, whole RNA sequencing and targeted array capture sequencing approaches.
We have isolated >50,000 DNA samples (biobanking), generated >100,000 GWAS samples, >5,000 DNA methylation array samples, >20,000 NGS samples (Exome, RNA Seq, ChIPSeq, 3C) focused on complex human genetics of major common diseases in large cohort studies, such as the Rotterdam Study, as well as a variety of fundamental research lines. The facility is among the top 3 facilities for NGS and genotyping in Europe. For the production of NGS data we are running Illumina sequencing platforms, and have a dedicated bioinformatics team to analyse, interpret and vizualize the data. The recently expanded computing/data-storage hardware infrastructure encompassing 1,000 cores and >2 petabyte storage enables bioinformatics services for NGS data analyses as well as GWAS data analyses. The data created from the cohort studies serve as reference data in case-control analyses by external parties, and as reference for internal variant filtering both for research and diagnostics. Finally, the Rotterdam Genomics Core has implemented next generation sequencing in diagnostics and performs it for the Erasmus MC Clinical Genetics department under CCKL accreditation.
- Biomedical & health
- NGS: de novo genome sequencing, exome sequencing, targeted sequencing, RNA sequencing, ChIP sequencing, chromatin conformation sequencing, microbiome sequencing (16S, metagenomics)
- Microarray: GWAS SNP arrays, exome arrays, clinical diagnostics (SNP) arrays, methylation arrays, RNA expression arrays;Genotyping platforms: HT Taqman, sequenom
- DNA handling robots: DNA isolation, DNA normalization;Biobanking
- Bioinformatic data analysis of NGS data
- Clinical genetics
- Population genetics
- Technology development
Expertise and Track Record
435000021 The gut microbiota and childhood weight development: the role of the host genomeThe gut microbiota and childhood weight development: the role of the host genome with prof. dr. ir. I.C.W. Arts (Maastricht UMC). 435002025 Unlocking the value of 3D screening assays with gene expression profiling With Van de Water (Leiden University).
In the past 10 years our facilities have handled >100,000 human DNA/RNA samples both for research as well as clinical diagnostics more recently. Thereby we have become the largest facility in Netherlands and are now in the top 3 of such facilities in Europe. We have specialized in quickly implementing and developing novel genomics technology for research and clinical use, and especially so in large scale high throughput settings in cohort research. More recently our facility has been widely involved in clinical research and diagnostics running many projects or clinical departments in- but also out-side Erasmus MC.
On top of our technological expertise and capacities, we also offer access to the large epidemiological cohort study data, which function as reference and control data. These cohort studies are diverse (Rotterdam Study, Generation R Study, ERF), population-based (and thereby represent normal people), contain rich genomics data (NGS Exome, GWAS, RNA Seq, methylation) and are of very large sample size (n= 3,000 – 12,000). These cohort data are often used as control data in case-control comparison (where only cases are then offered to be genotyped in our facility). In addition, the population-based NGS data are used to filter variants in our NGS pipelines of NGS samples, with a special focus on filtering out the local/regional rare sequence variants. We therefore like to think these are quite unique resources, not only in NL but also on a global level.
1. NGS Cohort Exome Sequening: NGS analysis (sequencing, QC, variant calling) for whole exome sequencing (Nimblegenv2, Agilentv4) of ~5,000 DNA samples of two major Erasmus MC cohort studies: The Rotterdam Study and the ERF study (finished).
2. BBMRI Exome Array Project: handling and genotyping of ~40,000 samples on the Illumina exome array from all major Dutch BioBanks within 4 months (finished); BBMRI RNA Seq Project: handling and NGS analysis (Illumina HiSeq2000) of ~8,000 blood RNA samples of all major Dutch Biobanks within 1 year (ongoing); BBMRI Methylation Array Project: handling and methylation array (Illumina 450K) analysis of ~10,000 DNA samples of all major Dutch Biobanks (ongoing).
3. Clinical Diagnostics Array typing projects: Routine handling and genotyping of ~4,500 clinical DNA samples per year from the dept of Clinical Genetics (Erasmus MC) on the cyto12 SNP array (standing yearly contract). Non Invasive Prenatal Diagnostics (NIPD) application: identification of foetal aneuploidy in blood sample of pregnant women by NGS and subsequent analysis (Papassavva et al.,EJHG 2013 apr 10). Clinical targeted Sequencing: target capture of yearly 750 patient samples with either cardiomyopathy, neurodegenerative or ciliopathy diseases.
Please note :
a) We have a yearly turnover of >5 million euro for projects within within our facility. This number is quite constant over the past 5 years. On request we can provide more detail on activities per year in terms of number of samples and genomics services.
b) We have extensive publication track records involving our services, especially on GWAS and more recently also on NGS. For example, GWAS publications run into the hundreds including in all major scientific journals (such as Science, Nature, New Engl J Med, Lancet , JAMA, Nat Genetics, Nature Protocols ). We are happy to provide a more detailed bibliography upon request.
- Fungal volatile compounds induce production of the secondary metabolite Sodorifen in Serratia plymuthica PRI-2C. Schmidt R, Jager V, Zühlke D, Wolff C, Bernhardt J, Cankar K, Beekwilder J, Ijcken WV, Sleutels F, Boer W, Riedel K, Garbeva P. Sci Rep. 2017 Apr 13;7(1):862. doi: 10.1038/s41598-017-00893-3.
- Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Baar MP, Brandt RM, Putavet DA, Klein JD, Derks KW, Bourgeois BR, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RW, Madl T, Hoeijmakers JH, Campisi J, de Keizer PL. Cell. 2017 Mar 23;169(1):132-147.e16. doi: 10.1016/j.cell.2017.02.031.
BBMRI: We are the preferred technology service partner for the Dutch BBMRI Project (Exome Array project, RNA seq Project, methylation Project), involving handling > 50,000 samples so far;NGI: We are a preferred technology partner in several NGI consortia (NCHA, CMSB, VIRGO), providing NGS and microarray services, support and technology development;EU: We provide NGS and/or array services for several EU projects (coordinated actions, ERC grants; e.g., GEFOS, ENGAGE, PanCare, TAILORED, etc.).
- Affymetrix arrays
- Single cell Wafergen