Sebastian Kral
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Sebastian Kral has a total of 43 co-authors. Here are the top co-authors by number of shared publications:
- Albrecht Stenzinger
Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
1 shared publication Alexander Ott
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
1 shared publicationAndreas Blaumeiser
Center for Personalized Medicine (ZPM), Freiburg, Germany
1 shared publicationAnna Lena Illert
Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
1 shared publication- Axel Fürstberger
Institute of Medical Systems Biology, Ulm University, Ulm, Germany
1 shared publication - Axel Gschwind
Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany
1 shared publication
Latest Publications
- Open Access
- 20 October 2023
- Published by Springer Nature in npj Precision Oncology
- Vol. 7 (1) , 1-11
Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients
A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79–1, TMB: 0.97–0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.
- 20 October 2023
- Published by Springer Nature in npj Precision Oncology
- Vol. 7 (1) , 1-11
Open AccessMulticentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients
A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79–1, TMB: 0.97–0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.