| 1. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Reischer, G. H., et al.
(författare)
-
Performance Characteristics of qPCR Assays Targeting Human- and Ruminant-Associated Bacteroidetes for Microbial Source Tracking across Sixteen Countries on Six Continents
- 2013
-
Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:15, s. 8548-8556
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous quantitative PCR assays for microbial fecal source tracking (MST) have been developed and evaluated in recent years. Widespread application has been hindered by a lack of knowledge regarding the geographical stability and hence applicability of such methods beyond the regional level. This study assessed the performance of five previously reported quantitative PCR assays targeting human-, cattle-, or ruminant-associated Bacteroidetes populations on 280 human and animal fecal samples from 16 countries across six continents. The tested cattle-associated markers were shown to be ruminant-associated. The quantitative distributions of marker concentrations in target and nontarget samples proved to be essential for the assessment of assay performance and were used to establish a new metric for quantitative source-specificity. In general, this study demonstrates that stable target populations required for marker-based MST occur around the globe. Ruminant-associated marker concentrations were strongly correlated with total intestinal Bacteroidetes populations and with each other, indicating that the detected ruminant-associated populations seem to be part of the intestinal core microbiome of ruminants worldwide. Consequently tested ruminant-targeted assays appear to be suitable quantitative MST tools beyond the regional level while the targeted human-associated populations seem to be less prevalent and stable, suggesting potential for improvements in human-targeted methods.
|
|
| 3. |
- Ramirez, M. I., et al.
(författare)
-
Technical challenges of working with extracellular vesicles
- 2018
-
Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 881-906
-
Tidskriftsartikel (refereegranskat)abstract
- Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review. © 2018 The Royal Society of Chemistry.
|
|
| 4. |
- Björk, Göran, 1956, et al.
(författare)
-
Bathymetry and deep-water exchange across the central Lomonosov Ridge at 88°-89°N
- 2007
-
Ingår i: Deep-Sea Research I. - : Elsevier BV. ; 54, s. 1197-1208
-
Tidskriftsartikel (refereegranskat)abstract
- Seafloor mapping of the central Lomonosov Ridge using a multibeam echo-sounder during the Beringia/Healy–Oden Trans-Arctic Expedition (HOTRAX) 2005 shows that a channel across the ridge has a substantially shallower sill depth than the 2500 m indicated in present bathymetric maps. The multibeam survey along the ridge crest shows a maximum sill depth of about 1870 m. A previously hypothesized exchange of deep water from the Amundsen Basin to the Makarov Basin in this area is not confirmed. On the contrary, evidence of a deep-water flow from the Makarov to the Amundsen Basin was observed, indicating the existence of a new pathway for Canadian Basin Deep Water toward the Atlantic Ocean. Sediment data show extensive current activity along the ridge crest and along the rim of a local Intra Basin within the ridge structure.
|
|
| 5. |
- Jakobsson, Martin, et al.
(författare)
-
The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0
- 2012
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from similar to 6% in Version 2.0 to similar to 11% in Version 3.0. Citation: Jakobsson, M., et al. (2012), The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0, Geophys. Res. Lett., 39, L12609, doi:10.1029/2012GL052219.
|
|
| 6. |
- Rand, D.G., et al.
(författare)
-
Religious motivations for cooperation : An experimental investigation using explicit primes
- 2014
-
Ingår i: Religion, Brain and Behavior. - : Taylor & Francis (Routledge): STM, Behavioural Science and Public Health Titles. - 2153-599X. ; 4:1, s. 31-48
-
Tidskriftsartikel (refereegranskat)abstract
- The role of religion in human cooperation remains a highly contested topic. Recent studies using economic game experiments to explore this issue have been largely inconclusive, yielding a range of conflicting results. In this study, we investigate the ability of religion to promote cooperation by using explicit theological primes. In the first study, conducted in a church, we find that subjects who report a stronger connection with a Christian passage about charitable giving are subsequently more likely to cooperate in a one-shot prisoner's dilemma game. In the second study, conducted over the Internet, we find that Christian subjects are more likely to cooperate after reading a Christian passage than a neutral one. However, in the same study, we find that Hindu and secular passages have no significant effect on Christians, and that none of the passages (Christian, Hindu, or secular) have an effect on non-Christians. Our results show the potential power of explicitly religious exhortations that promote cooperation, and also their selectivity. © 2013 TaylorXX1Francis.
|
|
