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

Inclusion4EU: Towards a Framework of Inclusive Software Design Processes and Practices

This research is based on a trans-European research project aimed at enhancing software design and engineering practices to promote inclusivity, involving stakeholders from academia, industry, and disability advocacy services. To explore the nature and meaning of inclusion, a number of different approaches to inclusion are outlined, including models of equitable design (Accessible Design, Inclusive Design, Universal Design, and Design for All), User Design processes (Co-Production, Co-Creation, User-Centred Design, Co-Design, and Participatory Design), and Software Engineering Methodologies (Linear, Spiral, and Agile). These three categories of models are combined to form a three-dimensional environment in which software development projects can be mapped into to assess their level of inclusion. Finally, some case studies are presented to illustrate this new 3-D space in action

Network Hawkes Process Models for Exploring Latent Hierarchy in Social Animal Interactions

Group-based social dominance hierarchies are of essential interest in animal behavior research. Studies often record aggressive interactions observed over time, and models that can capture such dynamic hierarchy are therefore crucial. Traditional ranking methods summarize interactions across time, using only aggregate counts. Instead, we take advantage of the interaction timestamps, proposing a series of network point process models with latent ranks. We carefully design these models to incorporate important characteristics of animal interaction data, including the winner effect, bursting and pair-flip phenomena. Through iteratively constructing and evaluating these models we arrive at the final cohort Markov-Modulated Hawkes process (C-MMHP), which best characterizes all aforementioned patterns observed in interaction data. We compare all models using simulated and real data. Using statistically developed diagnostic perspectives, we demonstrate that the C-MMHP model outperforms other methods, capturing relevant latent ranking structures that lead to meaningful predictions for real data

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

Ethics4eu: Designing New Curricula For Computer Science Ethics Education: Case Studies For Ai Ethics

The computing ethics landscape is changing rapidly, as new technologies become more complex and pervasive, and people choose to interact with them in new and distinct ways. The resultant interactions are more novel and less easy to categorise using traditional ethical frameworks. It is important that developers of these technologies do not live in an ethical vacuum, that they think about the consequences of their creations, and take measures to prevent others being harmed by their work. To equip developers to rise to this challenge and create a positive future for the use of technology, it important that ethics becomes a central element of computer science education. To this end, the Ethics4EU project has developed curricula on a wide range of topics including privacy and agency of personal information, digital literacy, data governance and accountability, surveillance applications, algorithmic decision and automating human intelligence for robotics and autonomous vehicles. Crucially the content examines computing ethics, not only in terms of hardware and software, but how systems, people, organisations and society interact with technology.In this paper, we present our interdisciplinary approach to developing educational content for AI Ethics. This includes accessible teaching materials, in-class activities, sample assessments, practical guidelines and instructor guides. We discuss findings of an evaluation of the developed content with undergraduate computer science students

Wealth Building in Rural America: Potential in Human Diversity

Wealth Building in Rural America: Potential in Human Diversit

You Can\u27t Lose a Game If You Don\u27t Play the Game: Exploring the Ethics of Gamification in Education

Gamification has been hailed as a meaningful solution to the perennial challenge of sustaining student attention in class. It uses facets of gameplay in an educational context, including things such as points, leaderboards and badges. These are clearly efforts to make the student experience more entertaining and engaging, but nonetheless, they are also clearly digital nudges and attempts to change the students’ behaviours and attitudes to a specific set of concepts, and in which case they must, and should, be subject to the same ethical scrutiny as any other form of persuasion technique, as they may be unintentionally eroding the choices that students feel they have. This research therefore discusses some of the key ethical considerations and concerns associated with gamification, and presents a new framework that incorporates ethical tests into each stage of a pre-existing model of instructional design, that can be used when introducing gamification into an educational process