CRI iAtlas: an interactive portal for immuno-oncology research.

The Cancer Research Institute (CRI) iAtlas is an interactive web platform for data exploration and discovery in the context of tumors and their interactions with the immune microenvironment. iAtlas allows researchers to study immune response characterizations and patterns for individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports computation and visualization of correlations and statistics among features related to the tumor microenvironment, cell composition, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, expression of key immunomodulators, and tumor infiltrating lymphocyte (TIL) spatial maps. iAtlas was launched to accompany the release of the TCGA PanCancer Atlas and has since been expanded to include new capabilities such as (1) user-defined loading of sample cohorts, (2) a tool for classifying expression data into immune subtypes, and (3) integration of TIL mapping from digital pathology images. We expect that the CRI iAtlas will accelerate discovery and improve patient outcomes by providing researchers access to standardized immunogenomics data to better understand the tumor immune microenvironment and its impact on patient responses to immunotherapy

Non-pegmatitic beryl related to Carboniferous granitic magmatism, Velasco Range, Pampean Province, NW Argentina

The specialized leuco-monzogranite of the La Chinchilla Stock is a small Carboniferous stock located in the center of the Velasco Range, Pampean Province, La Rioja, Argentina. It is highly evolved and locally F- and Be-bearing, and has the potential for hosting U mineralization. Three different facies can be identified in the granitoid: border, porphyritic and equigranular facies. In all three facies the main minerals are quartz, microcline, plagioclase, biotite, and muscovite. Accessory minerals present in all facies include fluorite, zircon, and apatite. In addition, monazite, rutile, and uraninite occur as accessory minerals in the equigranular facies. Secondary minerals are muscovite, sericite, kaolinite, and opaque minerals. Secondary uranophane occurs in the equigranular and border facies. In localized areas, the equigranular facies contains small, green idiomorphic crystals of beryl (Be3Al2Si6O18) as accessory mineral. One of these beryl crystals was chemically analyzed for major and minor element contents using an electron microprobe and this information, along with fractional crystallization models and comparison with compositions of non-pegmatitic beryl from the literature, were used to understand the degree of evolution of the granitic melt. The chemical formula of beryl from the La Chinchilla Stock can be written as: C(Na0.014-0.033, K0.001-0.002, Ca0.001-0.004) T(2)(Be2.978-2.987, Li0.016-0.022) O(Al1.889-1.967, Fe0.045-0.103, Mg0.001-0.007, Mn0.001-0.007) T(1)(Si5.994-6.040O18). The alkali contents are low (Na2O6; FeOt<1.27 wt%). In a longitudinal geochemical profile, Al enrichment is observed at the border while the highest Na content is found in an internal point. In a transversal geochemical profile, the highest concentration of Al is seen in an internal point while Na remains almost invariable. Ferromagnesian elements vary randomly within the crystal. This indicates compositional changes in the magma for Al, ferromagnesian elements, and Na. The FeOt content of the analyzed beryl is within the compositional range of other disseminated beryl from granitoids but slightly higher than that of beryl from hydrothermal veins and greisens. It contains similar to slightly lower amounts of FeOt, MgO, and Na2O than beryl from medium to little evolved granitic pegmatites. Overall, the composition of beryl in the La Chinchilla Stock is quite similar to that from medium to poorly evolved granitic pegmatites of the nearby Velasco Pegmatite District. The formation of beryl in the La Chinchilla Stock is attributed to precipitation from a F-bearing, highly fractionated, Al- and Si-rich melt saturated in BeO. A fractional crystallization model using Rb and Ba suggests that the beryl-hosting rock crystallized from the parent melt after extreme fractionation and 75% crystallization. The occurrence of beryl as a magmatic accessory mineral in the equigranular facies of the La Chinchilla Stock is indicative of a very high degree of fractionation of the parental magma

Analytic pipelines to assess the relationship between immune response and germline genetics in human tumors.

Germline genetic variants modulate human immune response. We present analytical pipelines for assessing the contribution of hosts\u27 genetic background to the immune landscape of solid tumors using harmonized data from more than 9,000 patients in The Cancer Genome Atlas (TCGA). These include protocols for heritability, genome-wide association studies (GWAS), colocalization, and rare variant analyses. These workflows are developed around the structure of TCGA but can be adapted to explore other repositories or in the context of cancer immunotherapy. For complete details on the use and execution of this protocol, please refer to Sayaman et al. (2021)

Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality

Karlsson P, Droce A, Moser JM, et al. Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. International Journal Of Molecular Sciences. 2013;14(6):10908-10925.The identification of the mutation causing the phenotype of the amyotrophic lateral sclerosis (ALS) model mouse, wobbler, has linked motor neuron degeneration with retrograde vesicle traffic. The wobbler mutation affects protein stability of Vps54, a ubiquitously expressed vesicle-tethering factor and leads to partial loss of Vps54 function. Moreover, the Vps54 null mutation causes embryonic lethality, which is associated with extensive membrane blebbing in the neural tube and is most likely a consequence of impaired vesicle transport. Investigation of cells derived from wobbler and Vps54 null mutant embryos demonstrates impaired retrograde transport of the Cholera-toxin B subunit to the trans-Golgi network and mis-sorting of mannose-6-phosphate receptors and cargo proteins dependent on retrograde vesicle transport. Endocytosis assays demonstrate no difference between wobbler and wild type cells, indicating that the retrograde vesicle traffic to the trans-Golgi network, but not endocytosis, is affected in Vps54 mutant cells. The results obtained on wobbler cells were extended to test the use of cultured skin fibroblasts from human ALS patients to investigate the retrograde vesicle traffic. Analysis of skin fibroblasts of ALS patients will support the investigation of the critical role of the retrograde vesicle transport in ALS pathogenesis and might yield a diagnostic prospect

Germline genetic contribution to the immune landscape of cancer

Understanding the contribution of the host’s genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-β-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions.We are grateful to the Society for Immunotherapy of Cancer (SITC) for the logistical support of the investigator meeting within the SITC Cancer Immune Responsiveness Workshop (San Francisco CA, US, April 2018; Houston, TX, US, May 2019). We are also grateful to Noah Zaitlen and Andy Dahl for useful discussions on heritability interaction analyses. This work was funded in part by the National Institutes of Health R01CA227466 and K24CA169004 to EZ and T32CA221709 postdoctoral fellowship to RWS, Qatar National Research Fund (QNRF) NPRP11S-0121-180351 grant and the Sidra Precision Medicine Program internal grant (SDR100035 and SDR400023) to DB, Associazione Italiana per la Ricerca sul cancro (AIRC) grant IG2018-21846 to MC, the Cancer Research Institute funding to VT, and the Fundació Bancaria La Caixa, a La Caixa Junior Leader Fellowship (LCF/BQ/PI18/11630003) to EP-P.Peer ReviewedPostprint (author's final draft