| 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. |
- Currie, Thayne, et al.
(author)
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SCExAO/CHARIS Direct Imaging Discovery of a 20 au Separation, Low-mass Ratio Brown Dwarf Companion to an Accelerating Sun-like Star
- 2020
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 904:2
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Journal article (peer-reviewed)abstract
- We present the direct imaging discovery of a substellar companion to the nearby Sun-like star, HD 33632 Aa, at a projected separation of similar to 20 au, obtained with SCExAO/CHARIS integral field spectroscopy complemented by Keck/NIRC2 thermal infrared imaging. The companion, HD 33632 Ab, induces a 10.5 sigma astrometric acceleration on the star as detected with the Gaia and Hipparcos satellites. SCExAO/CHARIS JHK (1.1-2.4 mu m) spectra and Keck/NIRC2 L-p (3.78 mu m) photometry are best matched by a field L/T transition object: an older, higher-gravity, and less dusty counterpart to HR 8799 cde. Combining our astrometry with Gaia/Hipparcos data and archival Lick Observatory radial velocities, we measure a dynamical mass of 46.4 8 M-J and an eccentricity of e < 0.46 at 95% confidence. HD 33632 Ab's mass and mass ratio (4.0% 0.7%) are comparable to the low-mass brown dwarf GJ 758 B and intermediate between the more massive brown dwarf HD 19467 B and the (near-)planet-mass companions to HR 2562 and GJ 504. Using Gaia to select for direct imaging observations with the newest extreme adaptive optics systems can reveal substellar or even planet-mass companions on solar system-like scales at an increased frequency compared to blind surveys.
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| 3. |
- Kaufman, Darrell, et al.
(author)
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A global database of Holocene paleotemperature records
- 2020
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Journal article (peer-reviewed)abstract
- A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.
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