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- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 4. |
- Zheng, TH, et al.
(författare)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 6. |
- Crossfield, Ian J. M., et al.
(författare)
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197 CANDIDATES AND 104 VALIDATED PLANETS IN K2's FIRST FIVE FIELDS
- 2016
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 226:1
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Tidskriftsartikel (refereegranskat)abstract
- We present 197 planet candidates discovered using data from the first year of the NASA K2 mission (Campaigns 0-4), along with the results of an intensive program of photometric analyses, stellar spectroscopy, high-resolution imaging, and statistical validation. We distill these candidates into sets of 104 validated planets (57 in multi-planet systems), 30 false positives, and 63 remaining candidates. Our validated systems span a range of properties, with median values of R-P = 2.3 R-circle plus, P = 8.6 days, T-eff = 5300 K, and Kp = 12.7 mag. Stellar spectroscopy provides precise stellar and planetary parameters for most of these systems. We show that K2 has increased by 30% the number of small planets known to orbit moderately bright stars (1-4 R-circle plus, Kp = 9-13. mag). Of particular interest are 76 planets smaller than 2 R-circle plus, 15 orbiting stars brighter than Kp = 11.5. mag, 5 receiving Earth-like irradiation levels, and several multi-planet systems-including 4 planets orbiting the M dwarf K2-72 near mean-motion resonances. By quantifying the likelihood that each candidate is a planet we demonstrate that our candidate sample has an overall false positive rate of 15%-30%, with rates substantially lower for small candidates (<2 R-circle plus) and larger for candidates with radii >8 R-circle plus and/or with P < 3 days. Extrapolation of the current planetary yield suggests that K2 will discover between 500 and 1000 planets in its planned four-year mission, assuming sufficient follow-up resources are available. Efficient observing and analysis, together with an organized and coherent follow-up strategy, are essential for maximizing the efficacy of planet-validation efforts for K2, TESS, and future large-scale surveys.
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| 7. |
- Defrere, D., et al.
(författare)
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L'-band AGPM vector vortex coronagraph's first light on LBTI/LMIRCam
- 2014
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Ingår i: Adaptive Optics Systems IV. - : SPIE. - 9780819496164
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Konferensbidrag (refereegranskat)abstract
- We present the first observations obtained with the L'-band AGPM vortex coronagraph recently installed on LBTI/LMIRCam. The AGPM (Annular Groove Phase Mask) is a vector vortex coronagraph made from diamond subwavelength gratings. It is designed to improve the sensitivity and dynamic range of high-resolution imaging at very small inner working angles, down to 0.09 arcseconds in the case of LBTI/LMIRCam in the L' band. During the first hours on sky, we observed the young A5V star HR8799 with the goal to demonstrate the AGPM performance and assess its relevance for the ongoing LBTI planet survey (LEECH). Preliminary analyses of the data reveal the four known planets clearly at high SNR and provide unprecedented sensitivity limits in the inner planetary system (down to the diffraction limit of 0.09 arcseconds).
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| 9. |
- Geissbuehler, M., et al.
(författare)
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Triplet imaging of oxygen consumption during the contraction of a single smooth muscle cell (A7r5)
- 2012
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Ingår i: Oxygen Transport to Tissue XXXIII. - New York, NY : Springer Science+Business Media B.V.. - 9781461415657 ; , s. 263-268
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Konferensbidrag (refereegranskat)abstract
- Triplet imaging is a novel optical technique that allows investigating oxygen metabolism at the single cell and the sub-cellular level. The method combines high temporal and spatial resolutions which are required for the monitoring of fast kinetics of oxygen concentration in living cells. Calibration and validation are demonstrated with a titration experiment using l-ascorbic acid with the enzyme ascorbase oxidase. The method was applied to a biological cell system, employing as reporter a cytosolic fusion protein of β-galactosidase with a SNAP-tag labeled with tetramethylrhodamine. Oxygen consumption in single smooth muscle cells A7r5 during an [Arg8]-vasopressin- induced contraction is measured. The triplet lifetime images over time can be related to an intracellular oxygen consumption corresponding to a mono-exponentially decaying intracellular oxygen concentration. This is in good agreement with previously reported measurements of oxygen consumption in skeletal muscle fibers.
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| 10. |
- Hinz, A, et al.
(författare)
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Simulation of transients in heterogeneous catalysis: a comparison of the step- and pulse-transient techniques for the study of hydrocarbon oxidation on metal oxide catalysts
- 2000
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Ingår i: Chemical Engineering Science. - 0009-2509. ; 55:20, s. 4385-4397
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Tidskriftsartikel (refereegranskat)abstract
- The responses to step and pulse transients with reactants have been simulated for conventional step-transient conditions at atmospheric pressure and pulsing under vacuum using a temporal analysis of products (TAP) reactor, respectively. Propene oxidation over an oxide catalyst with the participation of lattice oxygen was chosen as a model reaction. The mechanism comprises adsorption of the reactants, a series of surface reaction steps and desorption of the products. For this type of reaction one of the reactants, namely oxygen, is a constituent of the catalyst and the oxygen coverage is assumed to be one at the start of the transient, Simulations were performed for all variants with one of the reaction steps becoming rate limiting at steady-state conditions. Both types of transients are compared for the same reaction mechanism and rate constants, neglecting catalyst restructuring. The results show that the visual features of step responses are often quite conclusive about the rate limiting step of the reaction mechanism, while pulse responses in this regard are less conclusive unless they are modelled or a desorption step is rate limiting. The two transient methods are compared regarding their usability for the study of reaction mechanisms. (C) 2000 Elsevier Science Ltd. All rights reserved.
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