EASI Genomics (European Advanced infraStructure for Innovative Genomics)

Next-generation sequencing (NGS) has taken modern research by storm and consequently is one of the most important tools of modern biological and biomedical research. However, the high cost of instrumentation and reagents, the multifaceted expertise required for correct use and the legal and ethical issues hamper access to NGS technologies for many researchers. EASI-Genomics addresses those challenges by unifying the major European genome centers that provide external access to their facilities. The mission of EASI-Genomics is to facilitate access to cutting-edge DNA sequencing technologies to researchers from both academia and industry, within a framework that ensures compliance with ethical and legal requirements, as well as FAIR and secure data management.

The GPCF Sequencing Unit performs low input whole-genome bisulfite sequencing (WGBS). Whole-genome bisulfite sequencing is the use of bisulfite treatment of whole genome DNA before routine sequencing to determine the pattern of methylation at a genome-wide scale.

The EASI genomics project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 824110.

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INFORM („INdividualized Therapy FOr Relapsed Malignancies in Childhood“)

The concept of the INFORM registry is to biologically characterize tumor samples (collected through routine standard of care biopsies at the time of the current tumor manifestation) for all pediatric patients with relapsed or refractory high risk disease of the 12 most common but also selected rare entities for whom no further standard of care therapy is available.

To get a fingerprint of the individual tumors, state-of-the-art genomic  technologies are applied , e.g.  exome and low coverage whole genome sequencing of tumor/normal pairs and RNA sequencing from tumors is performed by the GPCF Sequencing Unit and microarray based gene expression profiling and  methylation analysis is performed by the Microarray Unit.

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NCT MASTER (Molecularly Aided Stratification for Tumor Eradication)

The NCT “Precision Oncology Program” (POP) aims at the translation of latest research and technologies from the “OMICs” fields (genomics, transcriptomics, etc.) and systems biology/medicine into clinical practice. For example, genomic data obtained from next generation sequencing or microarray technologies provide a basis for the stratification of patients with the aim to predict the response to specific cancer therapies. Among other OMICS results, these data are discussed weekly by a Molecular Tumor Board composed of members with expertise in clinical oncology, pathology, molecular genetics, bioinformatics, medical genetics and counseling, pharmaceutics, and bioethics.

The GPCF Sequencing Unit performs whole genome and whole exome sequencing of tumor/normal pairs and RNA Sequencing of tumors within the NCT MASTER program.

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HIPO (“Heidelberg Center for Personalized Oncology”)

The “Heidelberg Center for Personalized Oncology” (DKFZ-HIPO) aims at clinically meaningful precision cancer medicine by applying state-of-the-art technologies that elucidate the molecular, cellular, and functional properties of individual human tumors. To this end, DKFZ-HIPO, the Division of Applied Bioinformatics, the DKFZ GPCF and bioinformatics groups on campus, and NCT POP work jointly on strategies for rapid-turnaround molecular profiling and streamlined data acquisition and analysis in a clinical setting.

The GPCF Sequencing Unit performs whole genome, whole exome and RNA Sequencing of tumors for those projects whereas the Microarray Unit contributes with Genotyping and Methylation Analysis.

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DKTK: German Cancer Consortium

Promising new cancer research findings need to reach clinical development and practice as quickly as possible. The German Cancer Consortium (DKTK), one of six German Health Research Centers (DZG), was founded in 2012 to support this aim. More than 20 academic research institutes and university hospitals at seven partner locations cooperate with DKFZ, the consortium’s core center.

Several DKTK projects are supported by the GPCF, e.g., mainly in the areas of high throughput sequencing and microarray technologies, but also by antibody production and making use of the vector and clone repository. Among other state-of-the-art sequencing technologies the Next-Generation Sequencing Unit offers the latest Illumina Hi-Seq X-Ten platform, which was funded by DKTK and allows whole genome sequencing of more than 3,000 patients per year. The genomics services are supported by a strong and well experienced local bioinformatics section.

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In this project (DZHK OMICs Resource DNA) the DKFZ together with the DZHK (Deutsches Zentrum für Herzkreislauf-Forschung e.V.) is sequencing the first large German cohort of healthy control individuals (>1200 persons) in order to identify genetic risk factors, placing the initial focus on cardiovascular diseases. The samples are provided by large established epidemiologic studies: Gutenberg Gesundheitsstudie (GHS), Hamburg City Health Study (HCHS), HD Supercontrols (HDSC), Kooperative Gesundheitsforschung in der Region Augsburg (KORA), Kohorte des Instituts für Klinische Molekularbiologie Kiel (IKMB), Study of Health in Pomerania (SHIP).

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DNA methylation-based CNS tumor classification

Based on their methylation profile CNS tumors can be clearly separated into groups closely matching histopathological entities. A software tool for non-bioinformaticians, ultimately to be made available via a secure web-based platform, has been developed to classify individual tumors of the central nervous system and to generate an accompanying confidence value. These results are used for the molecular classification of CNS malignancies, with likely impact on diagnostic/prognostic evaluation. The Microarray Unit has substantially contributed to the construction of this classifier by analyzing the reference cohort comprising over 2800 neuropathological tumors of almost all known entities.

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Molecular Neuropathology 2.0 - MNP2.0

The aim of the Germany-wide study "Molecular Neuropathology 2.0" is to improve the diagnostic accuracy in pediatric neurooncology by molecular analysis techniques. For this purpose, DNA methylation analysis is carried out for a molecular tumor classification of the tumor tissue in study patients in parallel to the established pathology assessment. In addition, GenPanel sequencing can uncover changes in the tumor genome that may help to more accurately diagnose or identify therapeutic targets. The GPCF Microarray-Unit performs DNA methylation analysis for this project.

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This long-term population-based cohort study of 8,000 colorectal cancer patients aims to assess the course, determinants and predictors of long-term outcomes (responsiveness to and tolerance of treatment, recurrence free, overall and disease-specific survival, overall and domain-specific quality of life) by age, gender, stage and other patient and tumor characteristics, with a particular focus on the prognostic impact of quality of care, comorbidity, co-medication, lifestyle factors, genetic predisposition, gene-therapy, gene-lifestyle, comorbidity-therapy and lifestyle-therapy interactions, and molecular cancer profiles. The primary goal is to identify potential approaches to enhance long-term prognosis and quality of life of CRC patients by targeted personalized prevention and therapy.  Overall, 450k methylation profiles should be generated from 2,200 CRC samples and 300 controls samples. This is done in the Microarray Unit of the Genomics and Proteomics Core Facility at DKFZ.

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DKFZ-Most Projekt Ca 175

The DKFZ - MOST (Ministry of Science, Technology & Space) program in cancer research aims at the establishment and enhancement of scientific collaboration between scientists from the DKFZ and all academic institutions in Israel.

The GPCF Bioinformatics Unit is involved in a DKFZ –MOST project which is targeted on studies of misregulation of alternative spicing (AS) in central nervous system ependymoma and breast cancer:

A strong connection was established between alternative splicing and carcinogenesis. Additionally, epigenetic determinants, such as histone modifications and DNA methylation, were also implicated in cancer formation and AS control. Deciphering the regulation of AS in cancer is therefore fundamental to our understanding of the disease and ways to combat it.

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