The Erasmus MC Bridge-meeting series bridges the gap between Biology, Technology and the Clinic. Each session combines one presentation on biology and one on bioinformatics/technology or a combination of both. The Bridge meeting is organized under the auspices of MolMed and will be chaired by Arne IJpma, dept. of Pathology, Unit Bioinformatics or Harmen van de Werken, Cancer Computational Biology Center. The meeting is organized each second Tuesday of the month and will start at 11.00 a.m. and will end around 12.30 p.m. Afterwards, we will serve our 'interactive’ lunch. After permission is granted by the the speaker, the presentation will be available for download from this intranet site. Please remember that these presentations are only meant within the Erasmus MC. If you wish to share it outside the Erasmus MC, please contact the speaker concerned directly.
|13-02-2018||Ralph Stadhouders||Department of Pulmonary Medicine||Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and|
Click for abstract
Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and MYC offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We have recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we used this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin-state dynamics. The results showed that TFs drive topological genome reorganization at multiple architectural levels, often before changes in gene expression. Removal of locus-specific topological barriers can explain why pluripotency genes are activated sequentially, instead of simultaneously, during reprogramming. Together, our results implicate genome topology as an instructive force for implementing transcriptional programs and cell fate in mammals.
|Ruben Boers||Department of Developmental Biology||Retrospective analysis of gene expression|
Click for abstract
Determination of the stem cell expression profile is a major focus in stem cell research. So far, technical difficulties hampered isolation of a pure population of stem cells required for proper characterization of a gene expression profile. Here we present a new method to analyze gene expression profiles of stem cells retrospectively without the requirement to isolate stem cells. In order to trace a stem cell expression profile we will use a fusion between the bacterial DNA cytosine methyltransferase (DCM) and different components of the RNA Polymerase II machinery. Mice have been generated with doxycyclin inducible fusion proteins, which methylate the CCWGG sequence in active genes. Pulse labeling active genes with a stable epigenetic mark that is propagated to daughter cells will allow retrospective analysis of gene expression.
|13-03-2018||Ross Kettleborough||Twist Bioscience||Synthetic Biology, applications and future vision|
Click for abstract
A special Bridge meeting: What would you do with 1M oligo’s? Join us at our Synthetic Biology Seminar on March 13! This Seminar will feature a presentation from Twist Bioscience’s European Technical Director Ross Kettleborough. A combination of science, networking and resource building. A great opportunity to meet Twist Bioscience and learn about our silicon-based DNA synthesis technology and latest developments in Gene synthesis, Protein Variant Libraries, CRISPR screening, NGS Human Core Exome Enrichment and future applications. Both research as well as diagnostic applications will be discussed. This seminar is hosted by Wilfred van IJcken, Erasmus MC Center for Biomics.
|10-04-2018||Joost Verlouw||Genetic Lab, HuGe-F genomics core facility & Department of Internal Medicine||Nanopore sequence technology: opportunities & limitations|
Click for abstract
Nanopore technology is a newcomer in the field of sequencing and does not work via the traditional sequencing-by-synthesis method but instead measures the nucleotides themselves. This opens up new possible applications which short read sequencing or polymerase based sequencing cannot provide. Examples of these applications are structural variant determination, measurement of complete haplotypes, direct RNA sequencing (transcript discovery), direct sequencing of DNA modification, complete 16S - or whole virus / virome – sequencing. However the user should be aware of several pitfalls of the technique which make it unreliable for, for example, determining individual single nucleotide variants. We recently acquired a GridION, which can run 5 MinION flowcells in parallel with real-time basecalling. The machine is available to all interested users within Erasmus MC, so knowledge on how to effectively use this new technique for different purposes can be pooled and shared.
|Wigard Kloosterman||Department of Medical Genetics, Center for Molecular Medicine, UMC Utrecht||Mapping and phasing of structural variations in human genomes using Nanopore sequencing|
Click for abstract
Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. I will highlight the analysis of human genome sequences using the MinION nanopore sequencer combined with a novel computational pipeline termed NanoSV. We demonstrate that nanopore long reads are superior to short reads with regard to detection of de novo complex chromosomal rearrangements. The long reads also enable efficient phasing of genetic variations, which we leveraged to improve SV calling, to determine the parental origin of de novo rearrangements and to resolve the structure of the rearrangements. Additionally, genome-wide surveillance of SVs reveals novel variants, missed in short-read data sets, a large proportion of which are retrotransposon insertions. We provide a first exploration of patient genome sequencing with a nanopore sequencer and demonstrate the value of long-read sequencing in mapping and phasing of SVs for both clinical and research applications.
|08-05-2018||Anton Koning||Department of Pathology; Unit Bioinformatics||Ae-406||N/A|
|11-09-2018||Najaf Amin||Department of Epidemiology||Ae-406||N/A|
|Tjakko van Ham||Department of Clinical Genetics||Ae-406||N/A|
|09-10-2018||Wilfred van IJcken||Center for Biomics||Ae-406||N/A|
|Peter Valk||Department of Hematology||Molecular Minimal Residual Disease in Acute Myeloid Leukemia||Ae-406||N/A|
|13-11-2018||Wiro Niessen||Department of Radiology & Medical informatics||Biomedical Imaging & Genetic (BIG) Data Analytics for Precision Medicine in Dementia & Oncology||Ae-406||N/A|
|11-12-2018||Athina Vidaki||Department of Genetic Identification||Epigenetic fingerprinting: Monitoring environmental response from life & health sciences to forensic applications||Ae-406||N/A|