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- In ’t Veld, Sjors G.J.G., et al.
(author)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Journal article (peer-reviewed)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Wain, Louise V, et al.
(author)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 3. |
- Jennings, Anne, et al.
(author)
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Modern and early Holocene ice shelf sediment facies from Petermann Fjord and northern Nares Strait, northwest Greenland
- 2022
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 283
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Journal article (peer-reviewed)abstract
- Based on sediment cores and geophysical data collected from Petermann Fjord and northern Nares Strait, NW Greenland, an Arctic ice shelf sediment facies is presented that distinguishes sub and pro ice shelf environments. Sediment cores were collected from sites beneath the present day Petermann Ice Tongue (PIT) and in deglacial sediments of northern Nares Strait with a focus on understanding the glacial and oceanographic history over the last 11,000 cal yr BP. The modern sub ice shelf sediment facies in Petermann Fjord is laminated and devoid of coarse clasts (IRD) due to strong basal melting that releases debris (debris filtering) from the basal ice at the grounding zone driven by buoyant subglacial meltwater and entrained Atlantic Water. Laminated sediments in the deep basin proximal to the gounding zone comprise layers of fine mud formed by suspension settling from turbid meltwater plumes (plumites) interrupted by normally graded very fine sand to medium silt layers with sharp basal contacts and rip-up clasts of mud, interpreted as turbidites. An inner fjord sill limits distribution of sediment gravity flows from the grounding zone to the deep inner fjord basin, such that sites on the inner sill and beyond the ice tongue largely only comprise plumites. Bioturbation and foraminiferal abundances increase with distance from the grounding zone. The benthic foraminiferal species, Elphidium clavatum is absent beneath the ice tongue, but dominant in the turbid meltwater influenced environment beyond the ice tongue. The very sparse IRD in sediments beneath the PIT and in the fjord beyond the PIT derives mainly from englacial debris in the ice tongue, side valley glaciers, rock falls from the steep fjord walls and sea ice.We use the modern ice shelf sediment facies characteristics to infer the past presence of ice shelves in northern Nares Strait using analyses of sediment cores from several cruises (OD1507, HLY03, 2001LSSL, RYDER19). On bathymetric highs, bioturbated mud with dispersed IRD overlies a 10–15 m thick, distinctly laminated silt and clay unit with rare coarse clasts and sparse foraminifera which forms a sediment drape of nearly uniform thickness. We interpret these laminated sediments to represent glaciomarine deposition by meltwater plumes emanating from ice streams that terminated in floating ice shelves. IRD layers, shifts in sediment composition (qXRD, MS and XRF) and faunal assemblage changes in the laminated unit document periods of ice-shelf instability sometimes, but not always, coupled with grounding zone retreat. Our deglacial reconstruction, including ice shelves, begins ∼10.7 cal ka BP, with confluent ice streams grounded in Hall Basin fronted by the Robeson Channel ice shelf. Ice shelf breakup and grounding zone retreat to relatively stable grounding zones at Kennedy Channel and the mouth of Petermann Fjord was accomplished by 9.4 cal ka BP when the Hall Basin ice shelf was established. This ice shelf broke up and reformed once prior to the final break up at 8.5 to 8.4 cal ka BP marking ice stream collapse, separation of Greenland and Innuitian ice sheets, and the opening of Nares Strait for Arctic-Atlantic throughflow. The Petermann ice shelf remained in Hall Basin until the Petermann Glacier retreated from the fjord mouth ∼7.1 cal ka BP. The resilience of these northern ice streams to strong early Holocene insolation and subsurface Atlantic Water advection is attributed to their northern aspect, buttressing by narrow passages, and high ice flux from the Greenland Ice Sheet (GIS).
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