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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Fresard, Laure, et al.
(author)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Journal article (peer-reviewed)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 4. |
- Soranno, Patricia A., et al.
(author)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Journal article (peer-reviewed)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 5. |
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| 6. |
- Thompson, Luke R., et al.
(author)
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A communal catalogue reveals Earth's multiscale microbial diversity
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 457-463
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Journal article (peer-reviewed)abstract
- © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
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| 7. |
- Antonova, M., et al.
(author)
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Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
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In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 12:07, s. 1-6
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Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. A near detector complex (ND280) is located 280 m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280’s measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
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| 8. |
- Antonova, M., et al.
(author)
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Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. Anear detector complex (ND280) is located 280m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280's measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
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| 9. |
- Antonova, M., et al.
(author)
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Proposal for characterization of muon spectrometers for neutrino beam lines with the Baby MIND
- 2015
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Reports (other academic/artistic)abstract
- Neutrino detectors based on state-of-the-art plastic scintillators read out with solid state photo-sensors, as well as new magnetization schemes, have been developed in the framework of AIDA. Meaningful size prototypes are under construction. In the framework of the CERN neutrino platform, we propose to test a Totally Active Scintillator Detector (TASD) and a prototype of a Magnetized Iron Neutrino Detector (MIND), called Baby MIND in the H8 beam line in 2016-2018. The design of the detectors and the purpose and plans for the beam tests are presented. An opportunity to use the Baby MIND detector in a real neutrino beam at JPARC for the measurement of the cross-section ratio between Water and scintillator (WAGASCI experiment) is described.
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| 10. |
- Antonova, M., et al.
(author)
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Synchronization of the distributed readout frontend electronics of the Baby MIND detector
- 2017
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In: 2017 XXVI International Scientific Conference Electronics (ET). - : IEEE. - 9781538617533
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Conference paper (peer-reviewed)abstract
- Baby MIND is a new downstream muon range detector for the WGASCI experiment. This article discusses the distributed readout system and its timing requirements. The paper presents the design of the synchronization subsystem and the results of its test.
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