Explore the vast range of titles available.

Background Improving our understanding of cancer and other complex diseases requires integrating diverse data sets and algorithms. Intertwining in vivo and in vitro data and in silico models are paramount to overcome intrinsic difficulties given by data complexity. Importantly, this approach also helps to uncover underlying molecular mechanisms. Over the years, research has introduced multiple biochemical and computational methods to study the disease, many of which require animal experiments. However, modeling systems and the comparison of cellular processes in both eukaryotes and prokaryotes help to understand specific aspects of uncontrolled cell growth, eventually leading to improved planning of future experiments. According to the principles for humane techniques milestones in alternative animal testing involve in vitro methods such as cell-based models and microfluidic chips, as well as clinical tests of microdosing and imaging. Up-to-date, the range of alternative methods has expanded towards computational approaches, based on the use of information from past in vitro and in vivo experiments. In fact, in silico techniques are often underrated but can be vital to understanding fundamental processes in cancer. They can rival accuracy of biological assays, and they can provide essential focus and direction to reduce experimental cost. Main body We give an overview on in vivo, in vitro and in silico methods used in cancer research. Common models as cell-lines, xenografts, or genetically modified rodents reflect relevant pathological processes to a different degree, but can not replicate the full spectrum of human disease. There is an increasing importance of computational biology, advancing from the task of assisting biological analysis with network biology approaches as the basis for understanding a cell’s functional organization up to model building for predictive systems. Conclusion Underlining and extending the in silico approach with respect to the 3Rs for replacement , reduction and refinement will lead cancer research towards efficient and effective precision medicine. Therefore, we suggest refined translational models and testing methods based on integrative analyses and the incorporation of computational biology within cancer research.

Background Understanding living systems is crucial for curing diseases. To achieve this task we have to understand biological networks based on protein-protein interactions. Bioinformatics has come up with a great amount of databases and tools that support analysts in exploring protein-protein interactions on an integrated level for knowledge discovery. They provide predictions and correlations, indicate possibilities for future experimental research and fill the gaps to complete the picture of biochemical processes. There are numerous and huge databases of protein-protein interactions used to gain insights into answering some of the many questions of systems biology. Many computational resources integrate interaction data with additional information on molecular background. However, the vast number of diverse Bioinformatics resources poses an obstacle to the goal of understanding. We present a survey of databases that enable the visual analysis of protein networks. Results We selected M =10 out of N =53 resources supporting visualization, and we tested against the following set of criteria: interoperability, data integration, quantity of possible interactions, data visualization quality and data coverage. The study reveals differences in usability, visualization features and quality as well as the quantity of interactions. StringDB is the recommended first choice. CPDB presents a comprehensive dataset and IntAct lets the user change the network layout. A comprehensive comparison table is available via web. The supplementary table can be accessed on http://tinyurl.com/PPI-DB-Comparison-2015 . Conclusions Only some web resources featuring graph visualization can be successfully applied to interactive visual analysis of protein-protein interaction. Study results underline the necessity for further enhancements of visualization integration in biochemical analysis tools. Identified challenges are data comprehensiveness, confidence, interactive feature and visualization maturing.

Sustainability in the context of machine learning (ML) plays an important role for accessible models by both researchers as well as clinicians. This article describes a reproducibility study on PiDeeL, a metabolic-pathway-informed deep learning model. It serves to test the hypothesis that the requirement of a simple provision of all digital artifacts is not sufficient to reproduce the computational experiment(s). The reproduction and modification of the computational model foundational to the previous findings shall promote documentation and evaluation of existing scientific models and confirm their applicability. The modification of the original model is based on measuring emissions of training machine learning models using CodeCarbon. Two different systems with different CPU as well as GPU specifications and Windows Subsystem Linux could be tested after guide and code adaptions due to initial incomplete replication attempts given the threshold of computation completion without error message(s). Emissions equivalent to 0.3–0.6 kg of CO2 per run were shown. Encountered issues along the replication attempts call for refined guidelines on documentation and processing of computational approaches in scientific studies by publishers as well as the scientific community. Thorough peer review including algorithmic reproduction would be necessary to ensure model reusability.

Objective Data sharing promotes the scientific progress. However, not all data can be shared freely due to privacy issues. This work is intended to foster FAIR sharing of sensitive data exemplary in the biomedical domain, via an integrated computational approach for utilizing and enriching individual datasets by scientists without coding experience. Methods We present an in silico pipeline for openly sharing controlled materials by generating synthetic data. Additionally, it addresses the issue of inexperience to computational methods in a non-IT-affine domain by making use of a cyberinfrastructure that runs and enables sharing of computational notebooks without the need of local software installation. The use of a digital twin based on cancer datasets serves as exemplary use case for making biomedical data openly available. Quantitative and qualitative validation of model output as well as a study on user experience are conducted. Results The metadata approach describes generalizable descriptors for computational models, and outlines how to profit from existing data resources for validating computational models. The use of a virtual lab book cooperatively developed using a cloud-based data management and analysis system functions as showcase enabling easy interaction between users. Qualitative testing revealed a necessity for comprehensive guidelines furthering acceptance by various users. Conclusion The introduced framework presents an integrated approach for data generation and interpolating incomplete data, promoting Open Science through reproducibility of results and methods. The system can be expanded from the biomedical to any other domain while future studies integrating an enhanced graphical user interface could increase interdisciplinary applicability.

In response to socioeconomic development, the number of machine learning applications has increased, along with the calls for algorithmic transparency and further sustainability in terms of energy efficient technologies. Modern computer algorithms that process large amounts of information, particularly artificial intelligence methods and their workhorse machine learning, can be used to promote and support sustainability; however, they consume a lot of energy themselves. This work focuses and interconnects two key aspects of artificial intelligence regarding the transparency and sustainability of model development. We identify frameworks for measuring carbon emissions from Python algorithms and evaluate energy consumption during model development. Additionally, we test the impact of explainability on algorithmic energy consumption during model optimization, particularly for applications in health and, to expand the scope and achieve a widespread use, civil engineering and computer vision. Specifically, we present three different models of classification, regression and object-based detection for the scenarios of cancer classification, building energy, and image detection, each integrated with explainable artificial intelligence (XAI) or feature reduction. This work can serve as a guide for selecting a tool to measure and scrutinize algorithmic energy consumption and raise awareness of emission-based model optimization by highlighting the sustainability of XAI.

Background Malignant brain tumor diseases exhibit differences within molecular features depending on the patient’s age. Methods In this work, we use gene mutation data from public resources to explore age specifics about glioma. We use both an explainable clustering as well as classification approach to find and interpret age-based differences in brain tumor diseases. We estimate age clusters and correlate age specific biomarkers. Results Age group classification shows known age specifics but also points out several genes which, so far, have not been associated with glioma classification. Conclusions We highlight mutated genes to be characteristic for certain age groups and suggest novel age-based biomarkers and targets.

Background A plethora of Web resources are available offering information on clinical, pre-clinical, genomic and theoretical aspects of cancer, including not only the comprehensive cancer projects as ICGC and TCGA, but also less-known and more specialized projects on pediatric diseases such as PCGP. However, in case of data on childhood cancer there is very little information openly available. Several web-based resources and tools offer general biomedical data which are not purpose-built, for neither pediatric nor cancer analysis. Additionally, many Web resources on cancer focus on incidence data and statistical social characteristics as well as self-regulating communities. Methods We summarize those resources which are open and are considered to support scientific fundamental research, while we address our comparison to 11 identified pediatric cancer-specific resources (5 tools, 6 databases). The evaluation consists of 5 use cases on the example of brain tumor research and covers user-defined search scenarios as well as data mining tasks, also examining interactive visual analysis features. Results Web resources differ in terms of information quantity and presentation. Pedican lists an abundance of entries with few selection features. PeCan and PedcBioPortal include visual analysis tools while the latter integrates published and new consortia-based data. UCSC Xena Browser offers an in-depth analysis of genomic data. ICGC data portal provides various features for data analysis and an option to submit own data. Its focus lies on adult Pan-Cancer projects. Pediatric Pan-Cancer datasets are being integrated into PeCan and PedcBioPortal. Comparing information on prominent mutations within glioma discloses well-known, unknown, possible, as well as inapplicable biomarkers. This summary further emphasizes the varying data allocation. Tested tools show advantages and disadvantages, depending on the respective use case scenario, providing inhomogeneous data quantity and information specifics. Conclusions Web resources on specific pediatric cancers are less abundant and less-known compared to those offering adult cancer research data. Meanwhile, current efforts of ongoing pediatric data collection and Pan-Cancer projects indicate future opportunities for childhood cancer research, that is greatly needed for both fundamental as well as clinical research.

Enhanced resolution of 7 T magnetic resonance imaging (MRI) scanners has considerably advanced our knowledge of structure and function in human and animal brains. Post-industrialized countries are particularly prone to an ever-increasing number of ageing individuals and ageing-associated neurodegenerative diseases. Neurodegenerative diseases are associated with volume loss in the affected brain. MRI diagnoses and monitoring of subtle volume changes in the ageing/diseased brains have the potential to become standard diagnostic tools. Even with the superior resolution of 7 T MRI scanners, the microstructural changes comprising cell types, cell numbers, and cellular processes, are still undetectable. Knowledge of origin, nature, and progression for microstructural changes are necessary to understand pathogenetic stages in the relentless neurodegenerative diseases, as well as to develop therapeutic tools that delay or stop neurodegenerative processes at their earliest stage. We illustrate the gap in resolution by comparing the identical regions of the post-mortem in situ 7 T MR images (virtual autopsy or virtopsy) with the histological observations in serial sections through the same brain. We also described the protocols and limitations associated with these comparisons, as well as the necessity of supercomputers and data management for “Big data”. Analysis of neuron and/or glial number by using a body of mathematical tools and guidelines (stereology) is time-consuming, cumbersome, and still restricted to trained human investigators. Development of tools based on machine learning (ML) and artificial intelligence (AI) could considerably accelerate studies on localization, onset, and progression of neuron loss. Finally, these observations could disentangle the mechanisms of volume loss into stages of reversible atrophy and/or irreversible fatal cell death. This AI- and ML-based cooperation between virtopsy and histology could bridge the present gap between virtual reality and neuropathology. It could also culminate in the creation of an imaging-associated comprehensive database. This database would include genetic, clinical, epidemiological, and technical aspects that could help to alleviate or even stop the adverse effects of neurodegenerative diseases on affected individuals, their families, and society.

The complexity of cancer diseases demands bioinformatic techniques and translational research based on big data and personalized medicine. Open data enables researchers to accelerate cancer studies, save resources and foster collaboration. Several tools and programming approaches are available for analyzing data, including annotation, clustering, comparison and extrapolation, merging, enrichment, functional association and statistics. We exploit openly available data via cancer gene expression analysis, we apply refinement as well as enrichment analysis via gene ontology and conclude with graph-based visualization of involved protein interaction networks as a basis for signaling. The different databases allowed for the construction of huge networks or specified ones consisting of high-confidence interactions only. Several genes associated to glioma were isolated via a network analysis from top hub nodes as well as from an outlier analysis. The latter approach highlights a mitogen-activated protein kinase next to a member of histondeacetylases and a protein phosphatase as genes uncommonly associated with glioma. Cluster analysis from top hub nodes lists several identified glioma-associated gene products to function within protein complexes, including epidermal growth factors as well as cell cycle proteins or RAS proto-oncogenes. By using selected exemplary tools and open-access resources for cancer research and differential network analysis, we highlight disturbed signaling components in brain cancer subtypes of glioma.

Purpose This contribution explores the underuse of artificial intelligence (AI) in the health sector, what this means for practice, and how much the underuse can cost. Attention is drawn to the relevance of an issue that the European Parliament has outlined as a \"major threat\" in 2020. At its heart is the risk that research and development on trusted AI systems for medicine and digital health will pile up in lab centers without generating further practical relevance. Our analysis highlights why researchers, practitioners and especially policymakers, should pay attention to this phenomenon. Methods The paper examines the ways in which governments and public agencies are addressing the underuse of AI. As governments and international organizations often acknowledge the limitations of their own initiatives, the contribution explores the causes of the current issues and suggests ways to improve initiatives for digital health. Results Recommendations address the development of standards, models of regulatory governance, assessment of the opportunity costs of underuse of technology, and the urgency of the problem. Conclusions The exponential pace of AI advances and innovations makes the risks of underuse of AI increasingly threatening. Graphical Abstract