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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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- De Witte, Nele A. J., et al.
(författare)
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Online consultations in mental healthcare during the COVID-19 outbreak : An international survey study on professionals' motivations and perceived barriers
- 2021
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: While the general uptake of e-mental health interventions remained low over the past years, physical distancing and lockdown measures relating to the COVID-19 pandemic created a need and demand for online consultations in only a matter of weeks.Objective: This study investigates the uptake of online consultations provided by mental health professionals during lockdown measures in the first wave of the COVID-19 pandemic in the participating countries, with a specific focus on professionals' motivations and perceived barriers regarding online consultations.Methods: An online survey on the use of online consultations was set up in March 2020. The Unified Theory of Acceptance and Use of Technology (UTAUT) guided the deductive qualitative analysis of the results.Results: In total, 2082 mental health professionals from Austria, Belgium, Cyprus, France, Germany, Italy, Lebanon, Lithuania, the Netherlands, Norway, Portugal, Spain, and Sweden were included. The results showed a high uptake of online consultations during the COVID-19 pandemic but limited previous training on this topic undergone by mental health professionals. Most professionals reported positive experiences with online consultations, but concerns about the performance of online consultations in a mental health context (e.g., in terms of relational aspects) and practical considerations (e.g., relating to privacy and security of software) appear to be major barriers that hinder implementation.Conclusions: This study provides an overview of the mental health professionals' actual needs and concerns regarding the use of online consultations in order to highlight areas of possible intervention and allow the implementation of necessary governmental, educational, and instrumental support so that online consultations can become a feasible and stable option in mental healthcare.
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