A deep learning classification task for brain navigation in rodents using micro-Doppler ultrasound imaging.

Positioning and navigation are essential components of neuroimaging as they improve the quality and reliability of data acquisition, leading to advances in diagnosis, treatment outcomes, and fundamental understanding of the brain. Functional ultrasound imaging is an emerging technology providing high-resolution images of the brain vasculature, allowing for the monitoring of brain activity. However, as the technology is relatively new, there is no standardized tool for inferring the position in the brain from the vascular images. In this study, we present a deep learning-based framework designed to address this challenge. Our approach uses an image classification task coupled with a regression on the resulting probabilities to determine the position of a single image. To evaluate its performance, we conducted experiments using a dataset of 51 rat brain scans. The training positions were extracted at intervals of 375 µm, resulting in a positioning error of 176 µm. Further GradCAM analysis revealed that the predictions were primarily driven by subcortical vascular structures. Finally, we assessed the robustness of our method in a cortical stroke where the brain vasculature is severely impaired. Remarkably, no specific increase in the number of misclassifications was observed, confirming the method's reliability in challenging conditions. Overall, our framework provides accurate and flexible positioning, not relying on a pre-registered reference but rather on conserved vascular patterns.

A software package for efficient patient trajectory analysis applied to analyzing bladder cancer development.

We present the Patient Trajectory Analysis Library (PTRA), a software package for explorative analysis of patient development. PTRA provides the tools for extracting statistically relevant trajectories from the medical event histories of a patient population. These trajectories can additionally be clustered for visual inspection and identifying key events in patient progression. The algorithms of PTRA are based on a statistical method developed previously by Jensen et al, but we contribute several modifications and extensions to enable the implementation of a practical tool. This includes a new clustering strategy, filter mechanisms for controlling analysis to specific cohorts and for controlling trajectory output, a parallel implementation that executes on a single server rather than a high-performance computing (HPC) cluster, etc. PTRA is furthermore open source and the code is organized as a framework so researchers can reuse it to analyze new data sets. We illustrate our tool by discussing trajectories extracted from the TriNetX Dataworks database for analyzing bladder cancer development. We show this experiment uncovers medically sound trajectories for bladder cancer.

Identifying and evaluating barriers for the implementation of machine learning in the intensive care unit.

BACKGROUND: Despite apparent promise and the availability of numerous examples in the literature, machine learning models are rarely used in practice in ICU units. This mismatch suggests that there are poorly understood barriers preventing uptake, which we aim to identify. METHODS: We begin with a qualitative study with 29 interviews of 40 Intensive Care Unit-, hospital- and MedTech company staff members. As a follow-up to the study, we attempt to quantify some of the technical issues raised. To perform experiments we selected two models based on criteria such as medical relevance. Using these models we measure the loss of performance in predictive models due to drift over time, change of available patient features, scarceness of data, and deploying a model in a different context to the one it was built in. RESULTS: The qualitative study confirms our assumptions on the potential of AI-driven analytics for patient care, as well as showing the prevalence and type of technical blocking factors that are responsible for its slow uptake. The experiments confirm that each of these issues can cause important loss of predictive model performance, depending on the model and the issue. CONCLUSIONS: Based on the qualitative study and quantitative experiments we conclude that more research on practical solutions to enable AI-driven innovation in Intensive Care Units is needed. Furthermore, the general poor situation with respect to public, usable implementations of predictive models would appear to limit the possibilities for both the scientific repeatability of the underlying research and the transfer of this research into practice.

It is helpful for clinicians to be able to predict what will happen to a patient in an Intensive Care Unit (ICU); accurate computer-based predictive systems could help to avoid serious illness. However, most ICUs currently make little or no use of them. Here, we try to understand why, so that barriers to their introduction can be overcome. We interview medical experts, who agree that prediction systems should be feasible. They also identify practical technical problems with using them. We investigate these issues by running experiments on example predictive systems where we change what data is used to train the system and what data it is asked to make predictions on. The experiments show that the identified issues cause problems and are worthy of further attention. This work should help to enable the use of computer-based predictive systems in ICUs.

Halvade somatic: Somatic variant calling with Apache Spark.

BACKGROUND: The accurate detection of somatic variants from sequencing data is of key importance for cancer treatment and research. Somatic variant calling requires a high sequencing depth of the tumor sample, especially when the detection of low-frequency variants is also desired. In turn, this leads to large volumes of raw sequencing data to process and hence, large computational requirements. For example, calling the somatic variants according to the GATK best practices guidelines requires days of computing time for a typical whole-genome sequencing sample. FINDINGS: We introduce Halvade Somatic, a framework for somatic variant calling from DNA sequencing data that takes advantage of multi-node and/or multi-core compute platforms to reduce runtime. It relies on Apache Spark to provide scalable I/O and to create and manage data streams that are processed on different CPU cores in parallel. Halvade Somatic contains all required steps to process the tumor and matched normal sample according to the GATK best practices recommendations: read alignment (BWA), sorting of reads, preprocessing steps such as marking duplicate reads and base quality score recalibration (GATK), and, finally, calling the somatic variants (Mutect2). Our approach reduces the runtime on a single 36-core node to 19.5 h compared to a runtime of 84.5 h for the original pipeline, a speedup of 4.3 times. Runtime can be further decreased by scaling to multiple nodes, e.g., we observe a runtime of 1.36 h using 16 nodes, an additional speedup of 14.4 times. Halvade Somatic supports variant calling from both whole-genome sequencing and whole-exome sequencing data and also supports Strelka2 as an alternative or complementary variant calling tool. We provide a Docker image to facilitate single-node deployment. Halvade Somatic can be executed on a variety of compute platforms, including Amazon EC2 and Google Cloud. CONCLUSIONS: To our knowledge, Halvade Somatic is the first somatic variant calling pipeline that leverages Big Data processing platforms and provides reliable, scalable performance. Source code is freely available.

Augmenting THerapeutic Effectiveness Through Novel Analytics (ATHENA) - A Public and Private Partnership Project Funded by the Flemish Government (VLAIO).

The complexity and heterogeneity of cancers leads to variable responses of patients to treatments and interventions. Developing models that accurately predict patient's care pathways using prognostic and predictive biomarkers is increasingly important in both clinical practice and scientific research. The main objective of the ATHENA project is to: (1) accelerate data driven precision medicine for two use cases - bladder cancer and multiple myeloma, (2) apply distributed and privacy-preserving analytical methods/ algorithms to stratify patients (decision support), (3) help healthcare professionals deliver earlier and better targeted treatments, and (4) explore care pathway automations and improve outcomes for each patient. Challenges associated with data sharing and integration will be addressed and an appropriate federated data ecosystem will be created, enabling an interoperable foundation for data exchange, analysis and interpretation. By combining multidisciplinary expertise and tackling knowledge gaps in ATHENA, we propose a novel federated privacy preserving platform for oncology research.

Multithreaded variant calling in elPrep 5.

We present elPrep 5, which updates the elPrep framework for processing sequencing alignment/map files with variant calling. elPrep 5 can now execute the full pipeline described by the GATK Best Practices for variant calling, which consists of PCR and optical duplicate marking, sorting by coordinate order, base quality score recalibration, and variant calling using the haplotype caller algorithm. elPrep 5 produces identical BAM and VCF output as GATK4 while significantly reducing the runtime by parallelizing and merging the execution of the pipeline steps. Our benchmarks show that elPrep 5 speeds up the runtime of the variant calling pipeline by a factor 8-16x on both whole-exome and whole-genome data while using the same hardware resources as GATK4. This makes elPrep 5 a suitable drop-in replacement for GATK4 when faster execution times are needed.

Qualification of a precision pattern dispenser.

In order to automate sample preparation processes, a precision pattern dispenser was designed to reproducibly dispense radioactive solutions at pre-defined positions. It is composed of an automatic liquid sample handling unit coupled to an XYZ table. Qualification tests were conducted to evaluate the performance of the instrument and to assess the compliance with the requirements, in particular trueness (< 2%) and repeatability (< 1%). The instrument allows preparing sources in different source holders and on air filters, in a fast and accurate way.

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays.

Selected ion flow tube-mass spectrometry for online monitoring of submerged fermentations: a case study of sourdough fermentation.

Selected ion flow tube-mass spectrometry (SIFT-MS) has recently gained interest as an alternative method to traditional GC-MS for the detection of targeted volatile sample compounds, due to its ease of use, its speed and sensitivity, and its potential for real-time quantification. The feasibility of this technique was demonstrated using the case of the production of ethanol during sourdough fermentation. The potential of SIFT-MS as an online monitoring device for food fermentations was further demonstrated by the detection of acetoin in certain sourdough fermentations. This allowed discrimination between sourdough fermentation processes and illustrated the importance of real-time monitoring of food fermentations.