An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Sedimentary cycles in a Mesoproterozoic aeolian erg-margin succession: Mangabeira Formation, Espinhaço Supergroup, Brazil

Aeolian systems were abundant and widespread in the early Proterozoic, post-2.2 Ga. However, the majority of aeolian successions of such great age are intensely deformed and are preserved only in a fragmentary state meaning that, hitherto, few attempts have been made to apply a sequence stratigraphic approach to determine mechanisms of aeolian construction, accumulation and preservation in such systems. The Mangabeira Formation is a well preserved Mesoproterozoic erg successions covering part of the São Francisco Craton, northeastern Brazil. The lower unit of the Mangabeira Formation (~ 500 m thick) comprises aeolian deposits of dune, interdune, and sand-sheet origin, as well as some of waterlain origin. These deposits are organized into vertically stacked depositional cycles, each 6 to 20 m thick, and characterized by aeolian sandsheet and waterlain deposits succeeded by aeolian dune and interdune deposits indicative of a drying-upward trend. Aeolian cross-strata exhibit a mean dip direction to the north. Each of these cycles likely arose in response to climatic oscillation from relatively humid to arid conditions, possibly related to orbital forcing. The lower unit of the Mangabeira Formation comprises up to 14 erg sequences. The accumulation and preservation of each was determined by the relative rate of water-table rise and the availability of sand for aeolian transport, both of which changed through time, resulting in the preservation of a succession of repeated drying-upward cycles

Produção de biomassa e rendimento de óleo essencial de folhas, galhos finos e rebrotas utilizando poda da copa de Aniba canelilla (H.B.K.) (Lauraceae) na Amazônia Central

Aniba canelilla (H.B.K.) Mez. is a tree species from Amazon that produces essential oil. The oil extraction from its leaves and stems can be an alternative way to avoid the tree cutting for production of essential oil. The aim of this study was to analyse factors that may influence the essential oil production and the biomass of resprouts after pruning the leaves and stems of A. canelilla trees. The tree crowns were pruned in the wet season and after nine months the leaves and stems of the remaining crown and the resprouts were collected, in the dry season. The results showed that the essential oil yield and chemical composition differed among the stems, leaves and resprouts. The stems' essential oil production differed between the seasons and had a higher production in the resprouting stems than the old stems of the remaining crown. The production of essential oil and leaf biomass of resprouts were differently related to the canopy openness, indicating that light increases the production of the essential oil and decreases the biomass of resprouting leaves. This study revealed that plant organs differ in their essential oil production and that the canopy openness must be taken into account when pruning the A. canelilla tree crown in order to achieve higher oil productivity.Aniba canelilla (H.B.K.) Mez. é uma espécie arbórea da Amazônia que produz óleo essencial. A extração do óleo de suas folhas e galhos pode ser uma forma alternativa de evitar a derrubada do tronco para sua produção de óleo essencial. O objetivo deste estudo foi analisar os fatores que podem influenciar a produção de óleo essencial e sua biomassa da rebrota após a poda de folhas e galhos das árvores de A. canelilla. As copas das árvores foram podadas na estação chuvosa e, após nove meses, as folhas e os galhos da copa remanescente e da rebrota foram coletadas na estação seca. Os resultados mostraram que o rendimento e a composição química de óleo essencial diferiram entre os galhos finos, as folhas e as rebrotas. A produção de óleo essencial de galhos diferiu entre as estações e teve maior produção nos galhos da rebrota do que nos galhos velhos da copa remanescente. A produção de óleo essencial e de biomassa das folhas da rebrota foram diferentemente relacionadas com a abertura de dossel, indicando que a luz aumenta a produção de óleo essencial e diminui a de biomassa nas folhas da rebrota. Este estudo revelou que as diferenças entre os órgãos da planta na produção de óleo essencial e a abertura de dossel devem ser levadas em consideração para podar a copa da árvore da A. canelilla e alcançar maior produtividade de óleo

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes