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Artificial Intelligence (AI) is already a reality in health systems, bringing benefits to patients, healthcare providers, and other stakeholders in the health care. To further leverage AI in health, Belgium is advised to make policy-level decisions about how to fund, design and undertake actions focussing on data access and inclusion, IT-infrastructure, legal and ethical frameworks, public and professional trust, in addition to education and interpretation. EU initiatives, such as European Health data space (EHDS), the Genomics Data Infrastructure (GDI) and the EU Cancer Imaging Infrastructure (EUCAIM) are building EU data infrastructures. To continue these positive developments, Belgium should continue to invest and support existing European data infrastructures. At the national level, a clear vision and strategy need to be developed and infrastructures need to be harmonized at the European level. [ABSTRACT FROM AUTHOR]

The liver is the primary site for the metabolism and detoxification of many compounds, including pharmaceuticals. Consequently, it is also the primary location for many adverse reactions. As the liver is not readily accessible for sampling in humans; rodent or cell line models are often used to evaluate potential toxic effects of a novel compound or candidate drug. However, relating the results of animal and in vitro studies to relevant clinical outcomes for the human in vivo situation still proves challenging. In this study, we incorporate principles of transfer learning within a deep artificial neural network allowing us to leverage the relative abundance of rat in vitro and in vivo exposure data from the Open TG-GATEs data set to train a model to predict the expected pattern of human in vivo gene expression following an exposure given measured human in vitro gene expression. We show that domain adaptation has been successfully achieved, with the rat and human in vitro data no longer being separable in the common latent space generated by the network. The network produces physiologically plausible predictions of human in vivo gene expression pattern following an exposure to a previously unseen compound. Moreover, we show the integration of the human in vitro data in the training of the domain adaptation network significantly improves the temporal accuracy of the predicted rat in vivo gene expression pattern following an exposure to a previously unseen compound. In this way, we demonstrate the improvements in prediction accuracy that can be achieved by combining data from distinct domains. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with substantial heterogeneity in its clinical presentation. This makes diagnosis and effective treatment difficult, so better tools for estimating disease progression are needed. Here, we report results from the DREAM-Phil Bowen ALS Prediction Prize4Life challenge. In this crowdsourcing competition, competitors developed algorithms for the prediction of disease progression of 1,822 ALS patients from standardized, anonymized phase 2/3 clinical trials. The two best algorithms outperformed a method designed by the challenge organizers as well as predictions by ALS clinicians. We estimate that using both winning algorithms in future trial designs could reduce the required number of patients by at least 20%. The DREAM-Phil Bowen ALS Prediction Prize4Life challenge also identified several potential nonstandard predictors of disease progression including uric acid, creatinine and surprisingly, blood pressure, shedding light on ALS pathobiology. This analysis reveals the potential of a crowdsourcing competition that uses clinical trial data for accelerating ALS research and development. [ABSTRACT FROM AUTHOR]

Background: The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics. Results: Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems. Conclusions: HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another. [ABSTRACT FROM AUTHOR]

In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of gene expression measured following an exposure in rodents to humans, circumventing the current reliance on orthologs, and also from in vitro to in vivo experimental designs. Of the applied deep learning architectures applied in this study the convolutional neural network (CNN) and a deep artificial neural network with bottleneck architecture significantly outperform classical machine learning techniques in predicting the time series of gene expression in primary human hepatocytes given a measured time series of gene expression from primary rat hepatocytes following exposure in vitro to a previously unseen compound across multiple toxicologically relevant gene sets. With a reduction in average mean absolute error across 76 genes that have been shown to be predictive for identifying carcinogenicity from 0.0172 for a random regression forest to 0.0166 for the CNN model (p < 0.05). These deep learning architecture also perform well when applied to predict time series of in vivo gene expression given measured time series of in vitro gene expression for rats., Competing Interests: The authors have declared that no competing interests exist.