Humans Infected with Relapsing Fever Spirochete Borrelia miyamotoi, Russia

Disease may occur throughout the world because of the widespread prevalence of this pathogen in ixodid ticks

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte

Photochemically-produced SO2_2 in the atmosphere of WASP-39b

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability. However, no unambiguous photochemical products have been detected in exoplanet atmospheres to date. Recent observations from the JWST Transiting Exoplanet Early Release Science Program found a spectral absorption feature at 4.05 $\mu$m arising from SO$_2$ in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 M$_J$) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of $\sim$1100 K. The most plausible way of generating SO$_2$ in such an atmosphere is through photochemical processes. Here we show that the SO$_2$ distribution computed by a suite of photochemical models robustly explains the 4.05 $\mu$m spectral feature identified by JWST transmission observations with NIRSpec PRISM (2.7$\sigma$) and G395H (4.5$\sigma$). SO$_2$ is produced by successive oxidation of sulphur radicals freed when hydrogen sulphide (H$_2$S) is destroyed. The sensitivity of the SO$_2$ feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of $\sim$10$\times$ solar. We further point out that SO$_2$ also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.Comment: 39 pages, 14 figures, accepted to be published in Natur

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies