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

Correlates of overall and central obesity in adults from seven European countries: findings from the Food4Me Study

To identify predictors of obesity in adults and investigate to what extent these predictors are independent of other major confounding factors. Data collected at baseline from 1441 participants from the Food4Me study conducted in seven European countries were included in this study. A food frequency questionnaire was used to measure dietary intake. Accelerometers were used to assess physical activity levels (PA), whereas participants self-reported their body weight, height and waist circumference via the internet. The main factors associated (p < 0.05) with higher BMI per 1-SD increase in the exposure were age (β:1.11 kg/m2), intakes of processed meat (β:1.04 kg/m2), red meat (β:1.02 kg/m2), saturated fat (β:0.84 kg/m2), monounsaturated fat (β:0.80 kg/m2), protein (β:0.74 kg/m2), total energy intake (β:0.50 kg/m2), olive oil (β:0.36 kg/m2), sugar sweetened carbonated drinks (β:0.33 kg/m2) and sedentary time (β:0.73 kg/m2). In contrast, the main factors associated with lower BMI per 1-SD increase in the exposure were PA (β:-1.36 kg/m2), intakes of wholegrains (β:-1.05 kg/m2), fibre (β:-1.02 kg/m2), fruits and vegetables (β:-0.52 kg/m2), nuts (β:-0.52 kg/m2), polyunsaturated fat (β:-0.50 kg/m2), Healthy Eating Index (β:-0.42 kg/m2), Mediterranean diet score (β:-0.40 kg/m2), oily fish (β:-0.31 kg/m2), dairy (β:-0.31 kg/m2) and fruit juice (β:-0.25 kg/m2). These findings are important for public health and suggest that promotion of increased PA, reducing sedentary behaviours and improving the overall quality of dietary patterns are important strategies for addressing the existing obesity epidemic and associated disease burden

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

Longitudinal river zonation in the tropics: examples of fish and caddisflies from endorheic Awash river, Ethiopia

Primary Research PaperSpecific concepts of fluvial ecology are well studied in riverine ecosystems of the temperate zone but poorly investigated in the Afrotropical region. Hence, we examined the longitudinal zonation of fish and adult caddisfly (Trichoptera) assemblages in the endorheic Awash River (1,250 km in length), Ethiopia. We expected that species assemblages are structured along environmental gradients, reflecting the pattern of large-scale freshwater ecoregions. We applied multivariate statistical methods to test for differences in spatial species assemblage structure and identified characteristic taxa of the observed biocoenoses by indicator species analyses. Fish and caddisfly assemblages were clustered into highland and lowland communities, following the freshwater ecoregions, but separated by an ecotone with highest biodiversity. Moreover, the caddisfly results suggest separating the heterogeneous highlands into a forested and a deforested zone. Surprisingly, the Awash drainage is rather species-poor: only 11 fish (1 endemic, 2 introduced) and 28 caddisfly species (8 new records for Ethiopia) were recorded from the mainstem and its major tributaries. Nevertheless, specialized species characterize the highland forests, whereas the lowlands primarily host geographically widely distributed species. This study showed that a combined approach of fish and caddisflies is a suitable method for assessing regional characteristics of fluvial ecosystems in the tropicsinfo:eu-repo/semantics/publishedVersio

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe