SEEDED - Sequencing Analysis of Epigenetic Deregulation in Disease

The SEEDED - Sequencing Analysis of Epigenetic Deregulation in Disease - summer school is targeted at PhD students and postdocs working in systems medicine projects like those conducted in the German e:Med program that involve deep sequencing (epi)genome and transcriptome analysis. SEEDED will train the participants on how to conduct the complete work-flow for the integrative analysis of epigenetic deregulation in primary disease cells. Complementary multi-readout data sets that map the DNA methylome, active enhancers or promoters as well as the transcriptome will be applied. In this manner SEEDED will advance the participants' skills for interdisciplinary work that combines experimental data acquisition and theoretical analysis. A specific focus will be on exploiting the multiple deep sequencing readouts for integrative systems medicine and personalized medicine approaches.

Candidates should provide an abstract on their current research as well as a letter of motivation for their application. The letter should described how the applicant's research would profit from attending the SEEDED course. A total of 14 participants will be selected that attend all three SEEDED modules described below. Selecting only one or two modules is not possible. There is no registration fee. For the selected participants all costs associated with course participation and accommodation will be covered by the program. Only travel to and from Heidelberg has to be organized and paid by the participants themselves.

SEEDED is funded by the Federal Ministry of Education and Research (BMBF) as a systems medicine training measure and involves the following three modules:

Module 1 - interactive lecture workshop, July, 13 – 15 2017, Crowne Plaza Heidelberg

Organizers: Karsten Rippe, Peter Lichter & Roland Eils

Module 1, the interactive lecture workshop will range from practical considerations on the experimental design and sample handling to the applications of deep sequencing analysis in (pre)clinical studies. It will lay out the basic framework and background training for the subsequent two practical courses and comprises the following topics:

  • Specific requirements of study design and medical applications that involve epigenomic analysis as compared to basic research with immortalized cell lines.
  • Integrative readout of chromatin and transcriptome features as a prerequisite for developing network models of epigenetic (de)regulation.
  • Mode of action and application of epigenetic drugs that perturb epigenetic signaling.
  • Quantitative data analysis as for example in differential DNA methylation of gene expression analysis.
  • ‘Use cases’ that describe how deep sequencing analysis of epigenetic deregulation is translated into (pre)clinical studies and clinical applications.

Module 2 - practical experimental course, July, 17. – 20, 2017, EMBL in Heidelberg, supported by Illumina

Organizers: Jan-Philipp Mallm, Vladimir Benes & Karsten Rippe

Module 2, the experimental integrated analysis of the functional epigenome will focus on addressing the technical challenges of analyzing epigenetic deregulation in primary human cells available at limited amounts. A combined whole-genome bisulfite sequencing (WGBS), ATAC-seq and RNA-seq analysis from the same sample will be donducted. With these readouts epigenetic signaling (WGBS), active and accessible enhancer and promoter sequences (ATAC-seq) and the functional consequences in terms of gene expression (RNA-seq) will be evaluated. The course will introduce protocols specifically adapted to the needs and limitations associated with the analysis of primary disease cells and healthy controls. The course will give an introduction to cell sample preparation and storage, an overview of sequencing library preparation methods from primary cells including trouble-shooting, pitfalls and necessary modifications and give standard protocols and variations of preparations of WGBS libraries, RNA-seq libraries  and ATAC-seq libraries as well as library sequencing.

The libraries generated in Module 2 will be sequenced and then analyzed by the participants in Module 3. Module 2 is organized in collaboration with the EMBL training course staff and with support from Illumina.

Module 3 - practical course on data analysis, September 27 - 29, 2017, conducted via the HD-HuB of the de.NBI program

Organizers: Benedikt Brors, Jan-Philipp Mallm & Karsten Rippe

Module 3, analyzing and interpreting RNA-seq, WGBS and ATAC-seq data will be a practical course with introductory seminars on the computational methods used. It will teach a hands-on workflow for the analysis of the sequencing data generated by the course participants in Module 2. It will be based on a rich multi-readout data set that allows it to address how DNA methylation, enhancer activity and transcription are correlated. A short introduction to basic computer skills (R, command line, etc.) needed in the course will be taught during the first day. Various analysis approaches applied in the context of reaching the learning goals in use workflows in R and Bioconductor. Sequence read mapping will also be covered in this part. On day 2 and 3, tools used for interpretation and visualization will be introduced, these include software for the identification and integrative analysis of differential gene expression, gene fusions and splicing variants as well as of epigenetic regulation of gene expression by differential methylation of CpG islands. Furthermore, the analysis of the active enhancer landscape from ATAC-seq data will be covered. The bioinformatical analysis taught in the course will serve as the foundation and starting point for developing integrative systems models that describe the function of epigenetic networks and effects that occur in response to treatment with epigenetic drugs that target chromatin modifiers.

The course will be part of the German Network for Bioinformatics Infrastructure (de.NBI) and conducted via the Heidelberg Center for Human Bioinformatics (HD-HuB) and its partner project on epigenetic analysis (de.NBI-epi).

Application deadline ends on May 28, 2017