Genotype Imputation from Large Reference Panels Das, Sayantan; Abecasis, Gonçalo R; Browning, Brian L
Annual review of genomics and human genetics,
08/2018, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Genotype imputation has become a standard tool in genome-wide association studies because it enables researchers to inexpensively approximate whole-genome sequence data from genome-wide ...single-nucleotide polymorphism array data. Genotype imputation increases statistical power, facilitates fine mapping of causal variants, and plays a key role in meta-analyses of genome-wide association studies. Only variants that were previously observed in a reference panel of sequenced individuals can be imputed. However, the rapid increase in the number of deeply sequenced individuals will soon make it possible to assemble enormous reference panels that greatly increase the number of imputable variants. In this review, we present an overview of genotype imputation and describe the computational techniques that make it possible to impute genotypes from reference panels with millions of individuals.
Avulsions involve switching of fluvial discharge through a new channel from an existing course and occur over varied timeframes ranging from hours to decades. With a peak discharge above ...100,000 m3/s, the Brahmaputra (2900 km) is one of the largest rivers in the world. Its lower course through the Ganga–Brahmaputra–Meghna (GBM) Delta of Bangladesh was first mapped in 1764–73 as a broad eastward-swinging curvature skirting the subsiding Sylhet Wetlands and falling into the Meghna River. Beginning from the late eighteenth century, the river started to avulse into a linear, more direct, southward passage into the Ganga called the Jamuna and decreased its length by 46 km (14.2%) from its former course to the Bay of Bengal. Examination of the established timeline and procedure of the avulsion event using maps and images from 1764–73, 1830–34, 1854–60, 1907–24, and 2014, in addition to evidence from contemporary literature and tree-ring reconstructed long-term discharge data, connoted certain discrepancies. Our re-evaluation indicated that the Brahmaputra shifted westward and was captured by a parallel distributary of the neighbouring Tista system initiating the switch. This was probably aided by exceptionally high monsoonal discharge between 1786 and 1790 as well as the 1787 break-in of the Tista into the Brahmaputra. Because of its high width:depth ratio and braided planform that prevented fast escape of the discharge, abandonment of the eastern channel—the ‘Old’ Brahmaputra—progressed gradually; well into the next century with the new channel taking over almost completely by 1855–60. Comparable switchings of the Brahmaputra occurred six times in the last 11 kyr and significantly influenced development of the GBM Delta. The century-scale timeline of the last avulsion event described here refines its current understanding by proposing river capture as the mechanism of avulsion, possibly triggered by clustering of high-flood years.
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•Channel avulsion in a delta occurs through a variety of processes and timescales.•The Brahmaputra alternately avulsed six times between two channels in the Holocene.•The latest event initiated as it was captured by a small stream flowing parallel to it.•Seemingly, consecutive occurrence of high-magnitude floods aided the break-in.•The avulsion process was gradual and continued for more than a century.
A convergent strategy for the stereoselective total synthesis of biologically active marine natural product biselyngbyolide B has been developed. Key strategies of this synthesis include Jamison ...protocol of trans-hydroalumination/allylation for installation of C18–C23 olefin moiety and intramolecular Heck coupling for macrocyclization.
The present work aims to evaluate distortion and residual stresses in thick plate weld joints of austenitic stainless steel. Quantification of residual stresses in thick austenitic stainless steel ...weld joint is important because it is not desirable to carry out stress relieving after welding owing to the susceptibility to sensitization in the heat-affected zone. Therefore, systematic studies were carried out to predict and measure distortion and residual stresses in the austenitic stainless steel plate weld joint. Variables influencing the generation of residual stresses such as heat input, welding speed, constraints during welding were considered. 20 mm thick plate weld joint of austenitic stainless steel material was prepared using gas tungsten arc welding (GTAW) in unclamped condition and distortions were measured during welding after each pass. Sub-surface and through-thickness residual stresses were measured using blind hole drilling (BHD) and deep hole drilling (DHD) techniques respectively. Thereafter, the weld joint was modeled using the finite element method and analyzed for residual stresses and distortions. Thermal analysis was carried out using actual welding parameters and temperature-dependent material properties to generate temperature profile and compare it with the measured values. The temperature profile along with necessary boundary conditions was used for structural analysis to obtain distortion and residual stresses. Experimental and finite element analysis results for distortion and residual stresses compare well. Details of the experimental and numerical analysis results of distortion and residual stresses for thick section plate weld joints have been discussed in this paper. Also, the effects of differences in yield strengths of weld and base metals on distortion and residual stress results have been brought out.
The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode ...offers significant advantages over fluorescence, mainly due to the superior signal‐to‐noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase. The activation of the prodrug in the presence of β‐galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β‐galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β‐galactosidase‐overexpressing tumor‐bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.
Ray of light: A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to a superior signal‐to‐noise ratio. A theranostic prodrug that is monitored through a chemiluminescence diagnostic mode was designed. As a representative example, a prodrug was prepared from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase.
Progress in GIS technology has facilitated the topographic position index (TPI)-based auto-classification of landform units. Multispectral satellite images, when used along with terrain analysis ...output, provide valuable information on structure, soil, land use land cover (LULC), hazards etc. The present work makes an endeavour to classify landforms using TPI and assess its distribution pattern across different LULC segments in the Kaljani River Basin of the Sub-Himalayan region. An attempt is also made to analyse the inundation pattern during the most recent major flood (2016) across the landform and LULC units.
The Kaljani Basin is occupied by upper slopes, mountain tops and gorges in its upper (northern) part, while its lower (southern) part is characterised by wide valleys and plains. The areas occupied by gorges and midslope drainages in the hills, and wide valleys in the foothills, are comparatively more exposed to fluvial erosion, as found from the topographic wetness index (TWI). LULC classification reveals that the northern and central parts of the basin have plenty of vegetation cover. Land use units like fallows, farmlands and built-up areas are more common in the southern part of the basin. During the flood of 2016, three-fourth of the total inundation occurred in the wide valleys and plains. More than 90% of the inundated areas are found in the human-modified terrain, indicating its susceptibility to the flood hazard.
Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight ...different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8
T-cells and CD4
T-cells including T
0, T
1 and T
17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10
). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.
The present work reports on the effect of thermal annealing on electrical, optical and structural properties of low aspect ratio self-organized TiO2 nanotube layers formed by anodization of Ti. The ...average inner diameter and length of the nanotubes was 100nm and 1μm, respectively. From the whole range of temperatures (300–600°C), annealing at 400°C leads to the formation of crystalline TiO2 nanotube layers with anatase structure offering best electrical and photo-electrochemical properties. Conducting atomic force microscopy studies have been explored for the first time to identify the annealing temperature of nanotube TiO2 layers with best electrical properties.
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