Measuring the State of Disaster Philanthropy 2015: Data to Drive Decisions

Jointly produced by Foundation Center and the Center for Disaster Philanthropy, Measuring the State of Disaster Philanthropy 2015: Data to Drive Decisions analyzes funding trends for disasters and humanitarian crises in 2013. In addition to examining U.S. foundation funding, this second annual report integrates other disaster-related funding data, including bilateral and multilateral aid, corporate giving, and online giving, to paint a more detailed picture of how institutional philanthropy is situated within the broader disaster funding landscape. Collectively, this report, along with the dashboard and mapping platform, provides donors, practitioners, and other stakeholders with in-depth information on funding flows for disasters and humanitarian crises. Explore more at disasterphilanthropy.org

A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations

Integrated Molecular Characterization of Uterine Carcinosarcoma

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

High-spectral resolution mid-UV spectrograph for Venus observing

International audienceInvestigating Venus' sulphur-oxide chemical cycle is highlighted as an important science target for Venus exploration because this cycle impacts radiative balance in Venus' atmosphere. In particular, it determines the abundance of S, O, SO, SO2 , and SO3 in the atmosphere; and it is the abundance of these species along with H2O that determines the rate of formation of the H2SO4 clouds that enshroud the planet. Additionally, the unknown UV absorber, which is expected to be responsible for more than 50% of the energy deposited to Venus mesosphere, is anticipated to be a sulphur-bearing compound [1], and its abundance is also expected to be linked to the sulphur-oxide cycle. Required Measurement: The two species that most directly map to the mechanisms that drive the sulfur-oxide cycle are the SO2 and SO gas species. Direct and simultaneous observation of the spatial distribution of these species as a function of local time, latitude and cloud motion in Venus' atmosphere can only be done below the clouds via in-situ observation. However, above the clouds these distributions can be derived from spectroscopic observations obtained in the mid-UV (between 190-240 nm) where the gas signatures of the two gases are isolated from the absorption signatures of other constituents prominent in Venus' atmosphere. Notably, at these wavelengths the absorption signatures of the two gases are strongly but not completely overlapping; to disentangle the bandheads of the 10Ȧ wide gas absorption bands, it is necessary to have both spectral sampling and the resolution of the sampling ≤ 2Ȧ. We are working to develop a compact & lightweight mid-UV spectrograph that will have sufficient spectral resolution (1.5 Ȧ) to segregate the gas signatures of the two gases and that can obtain reasonable spatial resolution of the planet disk from orbit around Venus as well as from a highly elliptical (perigee ~ 75000 km) Earth orbit. The spectral resolution of the proposed spectrograph will be 10x higher than that achieved by the UVS flown on the Pioneer Venus Orbiter, which was launched in 1978 [2]; and in fact, would be 10x higher than that acquired with any of the spectrographs flown to Venus within the last 40 years [3].The development and use of this type of UV spectrograph for space flight is long overdue , since in the most recent space-mission history the only UV spectrographs that have been flown in inter-planetary space with sensitivity to the 190-240 nm wavelength region are the Galileo UVS (15Ȧ spectral resolution) which was developed in the 1980s based on Voyager [4] the SPICAV and SPICAM instruments which aslo obtained 15Ȧ spectral resolution, and were included in the Venus and Mars Express payloads, respectively [3,5]; the MASCS/UVVS (50 Ȧ spectral resolution) included on the Messenger payload [6]; and the IUVS (5Ȧ spectral resolution) included on the MAVEN payload launched November 2013 [7]. Reference