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

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

Crop Updates 2005 - Cereals

This session covers thirty six papers from different authors: WHEAT AGRONOMY 1. Optimum sowing time of new wheat varieties in Western Australia, Darshan Sharma, Brenda Shackley, Mohammad Amjad, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 2. Wheat varieties updated in ‘Flowering Calculator’: A model predicting flowering time, B. Shackley, D. Tennant, D. Sharma and C.M. Zaicou-Kunesch, Department of Agriculture 3. Plant populations for wheat varieties, Christine M. Zaicou-Kunesch, Wal Anderson, Darshan Sharma, Brenda Shackley and Mohammad Amjad, Department of Agriculture 4. New wheat cultivars response to fertiliser nitrogen in four major agricultural regions of Western Australia, Mohammad Amjad, Wal Anderson, Brenda Shackley, Darshan Sharma and Christine Zaicou-Kunesch, Department of Agriculture 5. Agronomic package for EGA Eagle Rock, Steve Penny, Department of Agriculture 6. Field evaluation of eastern and western wheats in large-scale farmer’s trials, Mohammad Amjad, Ben Curtis and Veronika Reck, Department of Agriculture 7. New wheat varieties for a changing environment, Richard Richards, CSIRO Plant Industry; Canberra 8. Farmers can profitably minimise exposure to frost! Garren Knell, Steve Curtin and David Sermon, ConsultAg 9. National Variety Trials, Alan Bedggood, Australian Crops Accreditation System; Horsham 10. Preharvest-sprouting tolerance of wheat in the field, T.B. Biddulph1, T.L. Setter2, J.A. Plummer1 and D.J. Mares3; 1Plant Biology; FNAS, University of Western Australia; 2Department of Agriculture, 3School of Agriculture and Wine, University of Adelaide 11. Waterlogging induces high concentration of Mn and Al in wheat genotypes in acidic soils, H. Khabaz-Saberi, T. Setter, I. Waters and G. McDonald, Department of Agriculture 12. Agronomic responses of new wheat varieties in the Northern Agricultural Region, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 13. Agronomic responses of new wheat varieties in the Central Agricultural Region of WA, Darshan Sharma, Steve Penny and Wal Anderson, Department of Agriculture 14. EGA Eagle Rock tolerance to metribuzin and its mixtures, Harmohinder Dhammu, David Nicholson and Chris Roberts, Department of Agriculture 15. Herbicide tolerance of new bread wheats, Harmohinder Dhammu1 and David Nicholson2, Department of Agriculture NUTRITION 16. The impact of fertiliser placement, timing and rates on nitrogen-use efficiency, Stephen Loss, CSBP Ltd 17. Cereals deficient in potassium are most susceptible to some leaf diseases, Ross Brennan and Kith Jayasena, Department of Agriculture 18. Responses of cereal yields to potassium fertiliser type, placement and timing, Eddy Pol, CSBP Limited 19. Sulphate of Potash, the potash of choice at seeding, Simon Teakle, United Farmers Co-operative 20. Essential disease management for successful barley production, K. Jayasena, R. Loughman, C. Beard, B. Paynter, K. Tanaka, G. Poulish and A. Smith, Department of Agriculture 21. Genotypic differences in potassium efficiency of wheat, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 22. Genotypic differences in potassium efficiency of barley, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 23. Investigating timing of nitrogen application in wheat, Darshan Sharma and Lionel Martin, Department of Agriculture, and Muresk Institute of Agriculture, Curtin University of Technology 24. Nutrient timing requirements for increased crop yields in the high rainfall cropping zone, Narelle Hill, Ron McTaggart, Dr Wal Anderson and Ray Tugwell, Department of Agriculture DISEASES 25. Integrate strategies to manage stripe rust risk, Geoff Thomas, Robert Loughman, Ciara Beard, Kith Jayasena and Manisha Shankar, Department of Agriculture 26. Effect of primary inoculum level of stripe rust on variety response in wheat, Manisha Shankar, John Majewski and Robert Loughman, Department of Agriculture 27. Disease resistance update for wheat varieties in WA, M. Shankar, J.M. Majewski, D. Foster, H. Golzar, J. Piotrowski and R. Loughman, Department of Agriculture 28. Big droplets for wheat fungicides, Rob Grima, Agronomist, Elders 29. On farm research to investigate fungicide applications to minimise leaf disease impacts in wheat, Jeff Russell and Angie Roe, Department of Agriculture, and Farm Focus Consultants PESTS 30. Rotations for nematode management, Vivien A. Vanstone, Sean J. Kelly, Helen F. Hunter and Mena C. Gilchrist, Department of Agriculture 31. Investigation into the adaqyacy of sealed farm silos in Western Australia to control phosphine-resistant Rhyzopertha dominica, C.R. Newman, Department of Agriculture 32.Insect contamination of cereal grain at harvest, Svetlana Micic and Phil Michael, Department of Agriculture 33. Phosure – Extending the life of phosphine, Gabrielle Coupland and Ern Kostas, Co-operative Bulk Handling SOIL 34. Optimum combinations of ripping depth and tine spacing for increasing wheat yield, Mohammed Hamza and Wal Anderson, Department of Agriculture 35. Hardpan penetration ability of wheat roots, Tina Botwright Acuña and Len Wade, School of Plant Biology, University of Western Australia MARKETS 36. Latin America: An emerging agricultural powerhouse, Ingrid Richardson, Food and Agribusiness Research, Rabobank; Sydne

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth