Publications by authors named "Groth P"

FAIR Digital Object (FDO) is an emerging concept that is highlighted by European Open Science Cloud (EOSC) as a potential candidate for building an ecosystem of machine-actionable research outputs. In this work we systematically evaluate FDO and its implementations as a global distributed object system, by using five different conceptual frameworks that cover interoperability, middleware, FAIR principles, EOSC requirements and FDO guidelines themself. We compare the FDO approach with established Linked Data practices and the existing Web architecture, and provide a brief history of the Semantic Web while discussing why these technologies may have been difficult to adopt for FDO purposes.

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Background: Knowledge graphs (KGs) are an important tool for representing complex relationships between entities in the biomedical domain. Several methods have been proposed for learning embeddings that can be used to predict new links in such graphs. Some methods ignore valuable attribute data associated with entities in biomedical KGs, such as protein sequences, or molecular graphs.

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In this article, we describe a reproduction of the Relational Graph Convolutional Network (RGCN). Using our reproduction, we explain the intuition behind the model. Our reproduction results empirically validate the correctness of our implementations using benchmark Knowledge Graph datasets on node classification and link prediction tasks.

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Background: Electronic Laboratory Notebooks (ELNs) are used to document experiments and investigations in the wet-lab. Protocols in ELNs contain a detailed description of the conducted steps including the necessary information to understand the procedure and the raised research data as well as to reproduce the research investigation. The purpose of this study is to investigate whether such ELN protocols can be used to create semantic documentation of the provenance of research data by the use of ontologies and linked data methodologies.

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Many computational models rely on real-world data, and the steps required in moving from data collection, to data preparation, to model calibration, and input are becoming increasingly complex. Errors in data can lead to errors in model output that might invalidate conclusions in extreme cases. While the challenge of errors in data collection have been analyzed in the literature, here we highlight the importance of data handling in the modeling and simulation process, and how particular data handling errors can lead to errors in model output.

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Scientific data analyses often combine several computational tools in automated pipelines, or workflows. Thousands of such workflows have been used in the life sciences, though their composition has remained a cumbersome manual process due to a lack of standards for annotation, assembly, and implementation. Recent technological advances have returned the long-standing vision of automated workflow composition into focus.

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The web provides access to millions of datasets that can have additional impact when used beyond their original context. We have little empirical insight into what makes a dataset more reusable than others and which of the existing guidelines and frameworks, if any, make a difference. In this paper, we explore potential reuse features through a literature review and present a case study on datasets on GitHub, a popular open platform for sharing code and data.

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Reactive oxygen species (ROS) oxidize nucleotide triphosphate pools (e.g., 8-oxodGTP), which may kill cells if incorporated into DNA.

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A cross-disciplinary examination of the user behaviors involved in seeking and evaluating data is surprisingly absent from the research data discussion. This review explores the data retrieval literature to identify commonalities in how users search for and evaluate observational research data in selected disciplines. Two analytical frameworks, rooted in information retrieval and science and technology studies, are used to identify key similarities in practices as a first step toward developing a model describing data retrieval.

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The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anti-cancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-γH2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins.

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Robotic labs, in which experiments are carried out entirely by robots, have the potential to provide a reproducible and transparent foundation for performing basic biomedical laboratory experiments. In this article, we investigate whether these labs could be applicable in current experimental practice. We do this by text mining 1,628 papers for occurrences of methods that are supported by commercial robotic labs.

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Incidents that slow or stall replication fork progression, collectively known as replication stress, represent a major source of spontaneous genomic instability. Here, we determine the requirement for global protein biosynthesis on DNA replication and associated downstream signaling. We study this response side by side with dNTP deprivation; one of the most commonly used means to investigate replication arrest and replicative stress.

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Access to consistent, high-quality metadata is critical to finding, understanding, and reusing scientific data. However, while there are many relevant vocabularies for the annotation of a dataset, none sufficiently captures all the necessary metadata. This prevents uniform indexing and querying of dataset repositories.

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Article Synopsis
  • There is a strong need to make it easier to share and reuse scientific data among different groups like schools, companies, and publishers.
  • A new set of rules called the FAIR Data Principles has been created to help people make their data easier for both machines and humans to find and use.
  • This document is the first official introduction to the FAIR Principles and explains why they are important and gives examples of how they are being used.
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Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo.

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Article Synopsis
  • Modern drug discovery relies on integrated resources for effective decision-making and facilitating new findings, with a focus on pressing questions in the pharmaceutical industry.
  • The Open PHACTS Discovery Platform combines data about compounds, targets, pathways, and diseases to address complex drug discovery questions.
  • The platform offers computational workflows that provide solutions to these questions and makes them available for the scientific community through myExperiment.
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Replication inhibitors cause replication fork stalling and double-strand breaks (DSB) that result from processing of stalled forks. During recovery from replication blocks, the homologous recombination (HR) factor RAD51 mediates fork restart and DSB repair. HR defects therefore sensitize cells to replication inhibitors, with clear implications for cancer therapy.

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Model-based prediction is dependent on many choices ranging from the sample collection and prediction endpoint to the choice of algorithm and its parameters. Here we studied the effects of such choices, exemplified by predicting sensitivity (as IC50) of cancer cell lines towards a variety of compounds. For this, we used three independent sample collections and applied several machine learning algorithms for predicting a variety of endpoints for drug response.

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Article Synopsis
  • - Cancer chromosomal instability (CIN) leads to frequent changes in chromosome number and structure, resulting in diverse tumor cell populations and is linked to poor outcomes and drug resistance.
  • - In this study, researchers found that CIN(+) colorectal cancer (CRC) cells experience impaired DNA replication and increased replication stress compared to CIN(-) CRC cells, contributing to chromosome missegregation during cell division.
  • - The researchers identified three new genes that suppress CIN, which are often lost in CIN(+) CRC, and showed that addressing replication stress could reduce chromosome segregation errors, suggesting potential new treatment strategies to improve cancer outcomes.
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Motivation: Fusion genes result from genomic rearrangements, such as deletions, amplifications and translocations. Such rearrangements can also frequently be observed in cancer and have been postulated as driving event in cancer development. to detect them, one needs to analyze the transition region of two segments with different copy number, the location where fusions are known to occur.

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DNA interstrand crosslinks (ICLs) are highly toxic lesions that covalently link both strands of DNA and distort the DNA helix. Crosslinking agents have been shown to stall DNA replication and failure to repair ICL lesions before encountered by replication forks may induce severe DNA damage. Most knowledge of the ICL repair process has been revealed from studies in bacteria and cell extracts.

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Article Synopsis
  • Open PHACTS is a collaboration among academia, publishers, SMEs, and pharmaceutical companies aimed at creating an open pharmacological space using advanced semantic web technologies.
  • The project focuses on developing practical applications to improve drug discovery research in both academic and industrial settings.
  • The paper discusses the challenges of drug discovery and how Open PHACTS plans to tackle these challenges through technical solutions and social collaboration.
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