Daniel Hübschmann is a physician and bioinformatician and heads the Innovation and Service Unit for Bioinformatics and Precision Medicine at the DKFZ; together with Marc Zapatka, he leads the Computational Oncology research group at the NCT/DKFZ in Heidelberg as well as the former early-career research group “Pattern Recognition & Digital Medicine” at the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM). His research focuses on pattern recognition in high-dimensional genomic data, the integration of clinical, multi-omics, and single-cell data for precision oncology, the quantitative analysis of cellular interactions, and digital decision-support and visualization systems for molecular tumor boards.

Marc Zapatka is a bioinformatician and co-leads the Computational Oncology research group with Daniel Hübschmann. His research focuses on computational cancer genomics: the analysis of next-generation sequencing data, the identification of driver mutations and structural variants, and the development of robust, reproducible analysis pipelines for large cohorts. He is involved in numerous international consortium projects, including those on the landscape of viral associations in human cancers and on pediatric tumors.

CO provides the bioinformatics analysis foundation for key precision oncology programs of the DKTK/NCT:

• MASTER (Molecularly Aided Stratification for Tumor Eradication Research): a program for patients with advanced rare tumors or unusually early-onset, otherwise incurable cancers. It combines genome, transcriptome, and methylation analyses with rapid clinical feedback to the molecular tumor boards at the NCT sites in Heidelberg and Dresden, as well as other DKTK partner sites.
• CATCH (Comprehensive Assessment of Clinical Features and Biomarkers To Identify Patients with Advanced or Metastatic Breast Cancer for Marker-Driven Trials in Humans): creates genotype and biomarker profiles of metastases in advanced/metastatic breast cancer to identify therapy-relevant driver mutations to inform treatment decisions.
• COGNITION: (Comprehensive assessment of clinical features, genomics, and further molecular markers to identify patients with early breast cancer for enrollment in marker-driven trials) applies the same approach to early-stage breast cancer in patients with an inadequate response to neoadjuvant therapy and establishes the molecular basis for the subsequent intervention study COGNITION-GUIDE.

The analyses provided are also used for clinical trials, including those from the NCT’s OCT2 program:

• COGNITION-GUIDE 
  Trial Details: https://clinicaltrials.gov/study/NCT05332561
• CRAFT
  Trial Details: https://clinicaltrials.gov/study/NCT04551521
• RATIONALE 
  Trial Details: https://clinicaltrials.gov/study/NCT06855134
• TOP-ART 
  Trial Details: https://clinicaltrials.gov/study/NCT03127215

The bioinformatics workflow encompasses the fundamental steps of NGS data analysis—alignment and quality control, somatic variant calling, and the pre-screening of clinically relevant and/or therapeutically targetable mutations. Based on the somatic variants of each tumor, a comprehensive annotation is performed against databases of drug targets, known driver mutations, and germline predisposition variants. The interpretation prioritizes potentially therapeutically relevant variants and links them to systemic cancer therapies; drawing on oncological expertise, the level of evidence from the literature and clinical trials is determined for each candidate mutation.

To accelerate and standardize this process, CO, in collaboration with the Secondary Use of Data in Oncology Group, has developed and operates the Knowledge Connector—a digital decision-support system that presents molecular findings in a structured format, links them to current expert knowledge, and thereby enables molecular tumor boards to conduct evidence-based, efficient evaluations. The system builds on an innovative knowledge base, the BoCKbase. This is based on the "Block of Clinical Knowledge" (BoCK) concept—an abstraction of the biomarker concept that enables the linking of evidence components. The system has been in use at the NCT sites in Heidelberg, Dresden, Berlin, and WERA (Augsburg) since 2022 and has already processed over 5,000 patient cases.

In addition to MTB analytics, CO is responsible for NGS analyses covering a broad spectrum of tumor entities and data types. The goal is to provide standardized, state-of-the-art data processing and analysis workflows. CO is currently developing and operating workflows for the centralized, standardized processing of:

• Alignment of whole-genome, whole-genome bisulfite, exome, ChIP, and RNA sequencing data (as well as variants of these technologies)
• somatic variant calling for single-nucleotide variants (SNVs), insertions and deletions (indels), structural variants (SVs), and copy number alterations (CNAs)
• methylation analyses
• cohort analyses such as oncoprint, mutational signatures, differential gene expression analysis, consensus partitioning
• single cell data analysis (scRNA-seq, CITE-seq, AB-seq, spatial expression, …)

In addition, CO develops resources for exploring high-dimensional datasets, self-learning cohort analysis tools, and machine learning methods for multiomics and single-cell data. The group is committed to responsible and reproducible bioinformatics practices and organizes training courses on translational bioinformatics analysis.

CO develops and maintains its code base in close collaboration with the Omics IT and Data Management Core Facility (ODCF, led by Ivo Buchhalter) and the Applied Bioinformatics Department (ABI, led by Benedikt Brors). As part of the molecular tumor boards, CO works closely with the clinical departments of Translational Medical Oncology (TMO, led by Stefan Fröhling) and Gynecologic Oncology / Breast Cancer (led by Andreas Schneeweiss).

Lab Management

• Dr. Katja Weichsel

Researchers

• Dr. German Demidov
• Dr. Fangyoumin Feng
• Dr. Martina Fröhlich
• Dr. Mario Hlevnjak
• Dr. Barbara Hutter
• Carola Kensche
• Polina Kozyulina
• Dr. Kübra Narci
• Dr. Malgorzata Oles
• Dr. Rajesh Pal
• Dr. Nagarajan Paramasivam
• Dr. Lorenzo Rigano
• Dr. Marc Rübsam
• Dr. David Schlütermann
• Dr. Anamika Thalor
• Dr. Ciğdem Hazal Timucin
• Dr. Shen Zhong

Quality Management Representatives

• Dr. Saskia Egarter
• Carola Leitner

Doctoral Students

• Anastasia Sedlmeier
• Sunidhi Sunidhi

Associate Members, Students

• Waqar Hussain
• Celine Krogmann
• Yejin Kwak
• Marco Rheinnecker
• Giulia Roeth
• Angelo Jovin Yamachui Sitcheu 

Alumni

• Dr. Jude al-Sabah
• Dr. Carolin Andresen
• Dr. Zuguang Gu
• Dr. Jennifer Hüllein
• Dr. Lea Jopp-Saile
• Dr. Sebastian Pirmann
• Dr. Sebastian Uhrig