Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Selective dendritic localization of mRNA in drosophila mushroom body output neurons

Memory-relevant neuronal plasticity is believed to require local translation of new proteins at synapses. Understanding this process requires the visualization of the relevant mRNAs within these neuronal compartments. Here, we used single-molecule fluorescence in situ hybridization to localize mRNAs at subcellular resolution in the adult Drosophila brain. mRNAs for subunits of nicotinic acetylcholine receptors and kinases could be detected within the dendrites of co-labeled mushroom body output neurons (MBONs) and their relative abundance showed cell specificity. Moreover, aversive olfactory learning produced a transient increase in the level of CaMKII mRNA within the dendritic compartments of the g5b’2a MBONs. Localization of specific mRNAs in MBONs before and after learning represents a critical step towards deciphering the role of dendritic translation in the neuronal plasticity underlying behavioral change in Drosophila.Team Raf Van de PlasApplied Science

A processing chain for estimating crop biophysical parameters using temporal Sentinel-1 synthetic aperture radar data in cloud computing framework

Biophysical parameters are descriptors of crop growth and production estimates. Retrieval of these biophysical parameters from synthetic aperture radar sensors at operational scales is highly interesting given the increase in access to data from radar missions. Vegetation backscattering can be simulated using the water cloud model (WCM). Crop biophysical parameters are obtained by inverting this model. However, the inversion problem is ill-posed, and existing methods, which include the lookup table (LUT) and iterative search algorithms, are often computationally intensive and lack good generalization capacity. This might make retrieval of the biophysical parameters computationally intensive for large study areas. In addition, the new generation of operational missions, which are often associated with a large volume of data, poses a challenge for estimating crop parameters. In this work, we use the cloud computing potentials of the Google Earth Engine (GEE) to demonstrate a unified processing pipeline for WCM inversion. The processing pipeline (GEE4Bio) uses Sentinel-1 radar measurements for WCM inversion and subsequently produces crop biophysical maps. Inversion is achieved by employing Random Forest regression, which is trained with radar backscatter measurements at Vertical transmit and vertical receive (VV) and Vertical transmit and horizontal receive (VH) channels. The model is trained and validated with independent calibration and validation datasets consisting of ground measurements for five major crops over the Joint Experiment for Crop Assessment and Monitoring–Carman test site in Canada. The inversion accuracies indicate strong correlation coefficients (r) of 0.83 and 0.87, with the estimated and in situ measured plant area index and wet biomass, respectively, with low root mean square error values. The GEE4Bio processing chain produced crop inventory maps with a reasonable time and apprehended the variability in plant growth across the test site.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Mathematical Geodesy and Positionin

A comparison between support vector machine and water cloud model for estimating crop leaf area index

The water cloud model (WCM) can be inverted to estimate leaf area index (LAI) using the intensity of backscatter from synthetic aperture radar (SAR) sensors. Published studies have demonstrated that the WCM can accurately estimate LAI if the model is effectively calibrated. However, calibration of this model requires access to field measures of LAI as well as soil moisture. In contrast, machine learning (ML) algorithms can be trained to estimate LAI from satellite data, even if field moisture measures are not available. In this study, a support vector machine (SVM) was trained to estimate the LAI for corn, soybeans, rice, and wheat crops. These results were compared to LAI estimates from the WCM. To complete this comparison, in situ and satellite data were collected from seven Joint Experiment for Crop Assessment and Monitoring (JECAM) sites located in Argentina, Canada, Germany, India, Poland, Ukraine and the United States of America (U.S.A.). The models used C-Band backscatter intensity for two polarizations (like-polarization (VV) and cross-polarization (VH)) acquired by the RADARSAT-2 and Sentinel-1 SAR satellites. Both the WCM and SVM models performed well in estimating the LAI of corn. For the SVM, the correlation (R) between estimated LAI for corn and LAI measured in situ was reported as 0.93, with a root mean square error (RMSE) of 0.64 m2m-2 and mean absolute error (MAE) of 0.51 m2m-2. The WCM produced an R-value of 0.89, with only slightly higher errors (RMSE of 0.75 m2m-2 and MAE of 0.61 m2m-2) when estimating corn LAI. For rice, only the SVM model was tested, given the lack of soil moisture measures for this crop. In this case, both high correlations and low errors were observed in estimating the LAI of rice using SVM (R of 0.96, RMSE of 0.41 m2m-2 and MAE of 0.30 m2m-2). However, the results demonstrated that when the calibration points were limited (in this case for soybeans), the WCM outperformed the SVM model. This study demonstrates the importance of testing different modeling approaches over diverse agro-ecosystems to increase confidence in model performance.Water Resource

‘You Are Here’: Visual Autobiographies, Cultural-Spatial Positioning, and Resources for Urban Living

This paper reports on a study of visual autobiographies produced in art workshops conducted in a variety of social contexts in East London with 19 research participants 11 women and girls, 8 men and boys – ranging from 10 to the 50s. From narrative analysis of the images, associated interviews, and field notes on the production and exhibition of the images, the paper argues that the study of cultural activity can allow us to identify cultural-spatial positionings related to, but also distinct from, socio-spatial positionings. Those cultural-spatial positionings indicate and in some cases produce cultural and symbolic resources that might not be discernable from other non-visual research data, that may differ importantly from participants’ socioeconomic resources, and that could usefully receive more attention. The study also suggests that transnationalism is strongly tied to people's narratives of their cultural lives within global cities, is critically articulated, and can be under-recognised when it is rooted in family

Artropolis 93 : Public Art and Art About Public Issues

Contains 12 texts and documents works by nearly 300 Canadian artists in a Vancouver-based public art project. Includes artist's statements. 7 bibl. ref