| 1. |
- 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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| 2. |
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| 3. |
- Czeszumski, Artur, et al.
(author)
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#EEGManyLabs: Investigating the Replicability of Influential EEG Experiments
- 2024
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Other publication (other academic/artistic)abstract
- There is growing awareness across the neuroscience community that the replicability of findings on the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardized analysis pipelines. Inspired by efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and selection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations.
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| 4. |
- Davenport, J., et al.
(author)
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Doses of darkness control latitudinal differences in breeding date in the barnacle Semibalanus balanoides
- 2005
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In: Journal of the Marine Biological Association of the United Kingdom. - 0025-3154. ; 85:1, s. 59-63
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Journal article (peer-reviewed)abstract
- This paper reports the first study of breeding in the boreo-arctic barnacle Semibalanus balanoides in which latitudinal variation in timing of egg mass hardening has been examined simultaneously over the geographical scale involved, thereby excluding temporal confounding of the data. The timing of autumn egg mass hardening on the middle shore was established in 2002 and 2003 at ten stations ranging latitudinally from Trondheim (63 degrees 24'N) to Plymouth (50 degrees 18'N). To assess variation at local scale (< 10 km), breeding was studied on three shores at each of two Irish locations (Cork and Galway). At Oban (Scotland) and Cork, the effect of shore height on timing of breeding was investigated. A strong influence of latitude and day length on timing of breeding was found in both 2002 and 2003. In both years, barnacles bred much earlier (when day length was longer) at high rather than low latitudes. No significant effect of environmental temperature or insolation on timing of breeding was detected. Shores no more than 10 km apart showed minimal difference in middle shore breeding date (< 4 days). However, upper shore barnacles bred significantly earlier (by 7-13 days) than middle shore animals. The data indicate that breeding is controlled by period of daily darkness, with high shore annuals encountering longer effective 'nights' because of the opercular closure response to emersion (which will reduce light penetration to tissues). Predictions concerning the effects of global changes in climate and cloud cover on breeding and population distribution are made. It is suggested that increased cloud cover in the northern hemisphere is likely to induce earlier breeding, and possibly shift the present southern limit of Semibalanus southwards.
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| 5. |
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| 6. |
- Snyder, Joel S., et al.
(author)
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#EEGManyLabs: Investigating the replicability of influential EEG experiments
- 2021
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In: Cortex. - : Elsevier. - 1973-8102 .- 0010-9452. ; 144, s. 213-229
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Journal article (peer-reviewed)abstract
- There is growing awareness across the neuroscience community that the replicability of findings about the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardised analysis pipelines. Inspired by recent efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalog-raphy (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound in-fluence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and se-lection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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