Simulating the interaction of galaxies and the intergalactic medium

The co-evolution of galaxies and the intergalactic medium as a function of environment is studied using hydrodynamic simulations of the ACDM cosmogony. It is demonstrated with non-radiative calculations that, in the absence of non-gravitational mechanisms, dark matter haloes accrete a near-universal fraction (~ 0.9Ω(_b)/ Ω (_m))of baryons. The absence of a mass or redshift dependence of this fraction augurs well for parameter tests that use X-ray clusters as cosmological probes. Moreover, this result indicates that non- gravitational processes must efficiently regulate the formation of stars in dark matter haloes if the halo mass function is to be reconciled with the observed galaxy luminosity function. Simulations featuring stellar evolution and non-gravitational feedback mechanisms (photo-heating by the ultraviolet background, and thermal and kinetic supemovae feedback) are used to follow the evolution of star formation, and the thermo- and chemo- dynamical evolution of baryons. The observed star formation history of the Universe is reproduced, except at low redshift where it is overestimated by a factor of a few, possibly indicating the need for feedback from active galactic nuclei to quench cooling flows around massive galaxies. The simulations more accurately reproduce the observed abundance of galaxies with late-type morphologies than has been reported elsewhere. The unique initial conditions of these simulations, based on the Millennium Simulation, allow an unprecedented study of the role of large-scale environment to be conducted. The cosmic star formation rate density is found to vary by an order of magnitude across the extremes of environment expected in the local Universe. The mass fraction of baryons in the observationally elusive warm-hot intergalactic medium (WHIM), and the volume filling factor that this gas occupies, is also shown to vary by a factor of a few across such environments. This variation is attributed to differences in the halo mass functions of the environments. Finally, we compare the X-ray properties of haloes from the simulations with the predictions of the White and Frenk (1991) analytic galaxy formation model, and demonstrate that deviations from the analytic prediction arise from the assumptions i) that haloes retain their cosmic share of baryons, and ii) their gas follows an isothermal density profile. The simulations indicate that a significant fraction of gas is ejected from low mass haloes by galactic superwinds, leading to a significant increase in their cooling time profiles and an associated drop in their soft X-ray luminosities, relative to the analytic model. Simulated X-ray luminosities remain greater than present observational upper limits, but it is argued that the observations provide only weak constraints and may suffer from a systematic bias, such that the mass of the halo hosting a given galaxy is overestimated. This bias also follows from the assumption that haloes exhibit isothermal density profiles

Galaxy mergers can initiate quenching by unlocking an AGN-driven transformation of the baryon cycle

We use zoom simulations to show how merger-driven disruption of the gas disc in a galaxy provides its central active galactic nucleus (AGN) with fuel to drive outflows that entrain and expel a significant fraction of the circumgalactic medium (CGM). This in turn suppresses replenishment of the interstellar medium, causing the galaxy to quench up to several Gyr after the merger. We start by performing a zoom simulation of a present-day star-forming disc galaxy with the EAGLE galaxy formation model. Then, we re-simulate the galaxy with controlled changes to its initial conditions, using the genetic modification technique. These modifications either increase or decrease the stellar mass ratio of the galaxy’s last significant merger, which occurs at z ≈ 0.74. The halo reaches the same present-day mass in all cases, but changing the mass ratio of the merger yields markedly different galaxy and CGM properties. We find that a merger can unlock rapid growth of the central supermassive black hole if it disrupts the co-rotational motion of gas in the black hole’s vicinity. Conversely, if a less disruptive merger occurs and gas close to the black hole is not disturbed, the AGN does not strongly affect the CGM, and consequently the galaxy continues to form stars. Our result illustrates how a unified view of AGN feedback, the baryon cycle and the interstellar medium is required to understand how mergers and quenching are connected over long timescales

DYNAMO-I. A sample of Ha-luminous galaxies with resolved kinematics

DYNAMO is a multiwavelength, spatially resolved survey of local (z ~ 0.1) star-forming galaxies designed to study evolution through comparison with samples at z ≃ 2. Half of the sample has integrated Hα luminosities of >1042 erg s-1, the typical lo

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

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

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

DYNAMO - I. A sample of H alpha-luminous galaxies with resolved kinematics

DYNAMO is a multiwavelength, spatially resolved survey of local (z ∼ 0.1) star-forming galaxies designed to study evolution through comparison with samples at z _ 2. Half of the sample has integrated Hα luminosities of >1042 erg s−1, the typical lower limit for resolved spectroscopy at z _ 2. The sample covers a range in stellar mass (109–1011M_) and star formation rate (0.2–100M_ yr−1). In this first paper of a series, we present integral-field spectroscopy of Hα emission for the sample of 67 galaxies. We infer gas fractions in our sample as high as _0.8, higher than typical for local galaxies. Gas fraction correlates with stellarmass in galaxies with star formation rates below 10M_ yr−1, as found by COLDGASS, but galaxies with higher star formation rates have higher than expected gas fractions. There is only a weak correlation, if any, between gas fraction and gas velocity dispersion. Galaxies in the sample visually classified as disc-like are offset from the local stellar mass Tully–Fisher relation to higher circular velocities, but this offset vanishes when both gas and stars are included in the baryonic Tully–Fisher relation. The mean gas velocity dispersion of the sample is_50 km s−1, and V/σ ranges from 2 to 10 for most of the discs, similar to ‘turbulent’ galaxies at high redshift. Half of our sample show disc-like rotation, while ∼20 per cent show no signs of rotation. The division between rotating and non-rotating is approximately equal for the sub-samples with either star formation rates >10M_ yr−1, or specific star formation rates typical of the star formation ‘main sequence’ at z _ 2. Across our whole sample, we find good correlation between the dominance of ‘turbulence’ in galaxy discs (as expressed by V/σ ) and gas fraction as has been predicted for marginally stable Toomre discs. Comparing our sample with many others at low- and high-redshift reveals a correlation between gas velocity dispersion and star formation rate. These findings suggest the DYNAMO discs are excellent candidates for local galaxies similar to turbulent z _ 2 disc galaxies

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types