Searching for transiting extra-solar planets at optical and radio wavelengths

This thesis is concerned with various aspects of the detection and characterisation of transiting extra-solar planets. The noise properties of photometric data from SuperWASP, a wide-field survey instrument designed to detect exoplanets, are investigated. There has been a large shortfall in the number of planets such transit surveys have detected, compared to previous predictions of the planet catch. It has been suggested that correlated, or red, noise in the photometry is responsible for this; here it is confirmed that red noise is present in the SuperWASP photometry, and its effects on planet discovery are quantified. Examples are given of follow-up photometry of candidate transiting planets, confirming that modestly-sized telescopes can rule out some candidates photometrically. A Markov-chain Monte Carlo code is developed to fit transit lightcurves and determine the depth of such lightcurves in different passbands. Tests of this code with transit data of WASP-3 b are reported. The results of a search for additional transiting planets in known transiting planetary systems are presented. SuperWASP photometry of 24 such systems is searched for additional transits. No further planets are discovered, but a strong periodic signal is detected in the photometry of WASP-10. This is ascribed to stellar rotational variation, the period of which is determined to be 11.91 ± 0.05 days. Monte Carlo modelling is performed to quantify the ability of SuperWASP to detect additional transiting planets; it is determined that there is a good (> 50 per cent) chance of detecting additional, Saturn-sized planets in P ~ 10 day orbits. Finally, the first-ever attempt to detect the secondary eclipse of a transiting extra-solar planet at radio wavelengths is made. Although no eclipse is conclusively detected, upper limits to the flux density from HD 189733 b are established, and compared to theoretical predictions of the flux due to electron-cyclotron maser emission

WASP-80b has a dayside within the T-dwarf range

AHMJT is a Swiss National Science Foundation (SNSF) fellow under grant number P300P2-147773. MG and EJ are Research Associates at the F.R.S-FNRS; LD received the support the support of the F.R.I.A. fund of the FNRS. DE, KH, and SU acknowledge the financial support of the SNSF in the frame of the National Centre for Competence in Research ‘PlanetS’. EH and IR acknowledge support from the Spanish Ministry of Economy and Competitiveness (MINECO) and the ‘Fondo Europeo de Desarrollo Regional’ (FEDER) through grants AYA2012-39612-C03-01 and ESP2013-48391-C4-1-R.WASP-80b is a missing link in the study of exo-atmospheres. It falls between the warm Neptunes and the hot Jupiters and is amenable for characterisation, thanks to its host star's properties. We observed the planet through transit and during occultation with Warm Spitzer. Combining our mid-infrared transits with optical time series, we find that the planet presents a transmission spectrum indistinguishable from a horizontal line. In emission, WASP-80b is the intrinsically faintest planet whose dayside flux has been detected in both the 3.6 and 4.5 $\mu$m Spitzer channels. The depths of the occultations reveal that WASP-80b is as bright and as red as a T4 dwarf, but that its temperature is cooler. If planets go through the equivalent of an L-T transition, our results would imply this happens at cooler temperatures than for brown dwarfs. Placing WASP-80b's dayside into a colour-magnitude diagram, it falls exactly at the junction between a blackbody model and the T-dwarf sequence; we cannot discern which of those two interpretations is the more likely. Flux measurements on other planets with similar equilibrium temperatures are required to establish whether irradiated gas giants, like brown dwarfs, transition between two spectral classes. An eventual detection of methane absorption in transmission would also help lift that degeneracy. We obtained a second series of high-resolution spectra during transit, using HARPS. We reanalyse the Rossiter-McLaughlin effect. The data now favour an aligned orbital solution and a stellar rotation nearly three times slower than stellar line broadening implies. A contribution to stellar line broadening, maybe macroturbulence, is likely to have been underestimated for cool stars, whose rotations have therefore been systematically overestimated. [abridged]Publisher PDFPeer reviewe

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

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

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

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research