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Digital pathology provides a possibility for computational analysis of histological slides and automatization of routine pathological tasks. Histological slides are very heterogeneous concerning staining, sections’ thickness, and artifacts arising during tissue processing, cutting, staining, and digitization. In this study, we digitally reproduce major types of artifacts. Using six datasets from four different institutions digitized by different scanner systems, we systematically explore artifacts’ influence on the accuracy of the pre-trained, validated, deep learning-based model for prostate cancer detection in histological slides. We provide evidence that any histological artifact dependent on severity can lead to a substantial loss in model performance. Strategies for the prevention of diagnostic model accuracy losses in the context of artifacts are warranted. Stress-testing of diagnostic models using synthetically generated artifacts might be an essential step during clinical validation of deep learning-based algorithms.

Background The massive amounts of data from next generation sequencing (NGS) methods pose various challenges with respect to data security, storage and metadata management. While there is a broad range of data analysis pipelines, these challenges remain largely unaddressed to date. Results We describe the integration of the open-source metadata management system iRODS (Integrated Rule-Oriented Data System) with a cancer genome analysis pipeline in a high performance computing environment. The system allows for customized metadata attributes as well as fine-grained protection rules and is augmented by a user-friendly front-end for metadata input. This results in a robust, efficient end-to-end workflow under consideration of data security, central storage and unified metadata information. Conclusions Integrating iRODS with an NGS data analysis pipeline is a suitable method for addressing the challenges of data security, storage and metadata management in NGS environments.

Next generation sequencing (NGS) has been a great success and is now a standard method of research in the life sciences. With this technology, dozens of whole genomes or hundreds of exomes can be sequenced in rather short time, producing huge amounts of data. Complex bioinformatics analyses are required to turn these data into scientific findings. In order to run these analyses fast, automated workflows implemented on high performance computers are state of the art. While providing sufficient compute power and storage to meet the NGS data challenge, high performance computing (HPC) systems require special care when utilized for high throughput processing. This is especially true if the HPC system is shared by different users. Here, stability, robustness and maintainability are as important for automated workflows as speed and throughput. To achieve all of these aims, dedicated solutions have to be developed. In this paper, we present the tricks and twists that we utilized in the implementation of our exome data processing workflow. It may serve as a guideline for other high throughput data analysis projects using a similar infrastructure. The code implementing our solutions is provided in the supporting information files.

Traditionally, the architecture of high-performance computing (HPC) systems is tailored for speed, while highly secure computer systems must sacrifice speed for security. However, a wide range of scientific domains, such as the life sciences, call for a combination of performance and security to allow processing sensitive data at scale. Here, we present RAMSES (Research Accelerator for Modeling and Simulation with Enhanced Security), an HPC system designed from the ground up to deliver high performance within a robust security framework. RAMSES integrates hardware-based memory encryption of AMD processors with state-of-the-art file encryption from IBM Storage Scale and the Thales CipherTrust manager, establishing an HPC platform that ensures continuous encryption throughout the data life cycle - at rest, in transit, and in use - in compliance with major data protection standards (European General Data Protection Regulation, ISO/IEC 27001 certification, and Federal Information Processing Standards). In addition, we implemented advanced operating system hardening, a multi-layered security architecture, and mandatory multi-factor authentication to adapt the HPC environment to increased security demands. Benchmark results from the biomedical sector demonstrate that the performance impact of the secure environment is limited and that integration of the conflicting requirements speed and security can be achieved while preserving a coherent, flexible, and user-friendly system.