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- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Shah, Nisha, et al.
(författare)
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Motivations for data sharing—views of research participants from four European countries : A DIRECT study
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438.
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore and compare different countries in what motivated research participants’ decisions whether to share their de-identified data. We investigated European DIRECT (Diabetes Research on Patient Stratification) research project participants’ desire for control over sharing different types of their de-identified data, and with who data could be shared in the future after the project ends. A cross-sectional survey was disseminated among DIRECT project participants. The results found that there was a significant association between country and attitudes towards advancing research, protecting privacy, and beliefs about risks and benefits to sharing data. When given the choice to have control, some participants (<50% overall) indicated that having control over what data is shared and with whom was important; and control over what data types are shared was less important than respondents deciding who data are shared with. Danish respondents indicated higher odds of desire to control data types shared, and Dutch respondents showed higher odds of desire to control who data will be shared with. Overall, what research participants expect in terms of control over data sharing needs to be considered and aligned with sharing for future research and re-use of data. Our findings show that even with de-identified data, respondents prioritise privacy above all else. This study argues to move research participants from passive participation in biomedical research to considering their opinions about data sharing and control of de-identified biomedical data.
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| 3. |
- Shah, Nisha, et al.
(författare)
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Sharing data for future research—engaging participants’ views about data governance beyond the original project : a DIRECT Study
- 2019
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 21:5, s. 1131-1138
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Biomedical data governance strategies should ensure that data are collected, stored, and used ethically and lawfully. However, research participants’ preferences for how data should be governed is least studied. The Diabetes Research on Patient Stratification (DIRECT) project collected substantial amounts of health and genetic information from patients at risk of, and with type II diabetes. We conducted a survey to understand participants’ future data governance preferences. Results will inform the postproject data governance strategy. Methods: A survey was distributed in Denmark, Sweden, The Netherlands, and the United Kingdom. Results: In total 855 surveys were returned. Ninety-seven percent were supportive of sharing data postproject, and 90% were happy to share data with universities, and 56% with commercial companies. The top three priorities for data sharing were highly secure database, DIRECT researchers to monitor data used by other researchers, and researchers cannot identify participants. Respondents frequently suggested that a postproject Data Access Committee should involve a DIRECT researcher, diabetes clinician, patient representative, and a DIRECT participant. Conclusion: Preferences of how data should be governed, and what data could be shared and with whom varied between countries. Researchers are considered as key custodians of participant data. Engaging participants aids in designing governance to support their choices.
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