Towards distributed reasoning for behavioral optimization

We propose an architecture which supports the behavioral self-optimization of complex systems. In this architecture we bring together specification-based reasoning and the framework of ant colony optimization (ACO). By this we provide a foundation for distributed reasoning about different properties of the solution space represented by different viewpoint specifications. As a side-effect of reasoning we propagate the information about promising areas in the solution space to the current state. Consequently the system’s decisions can be improved by considering the long term values of certain behavioral trajectories (given a certain situational horizon). We consider this feature to be a contribution to autonomic computing1st IFIP International Conference on Biologically Inspired Cooperative Computing - Biological Inspiration 1Red de Universidades con Carreras en Informática (RedUNCI

Towards distributed reasoning for behavioral optimization

We propose an architecture which supports the behavioral self-optimization of complex systems. In this architecture we bring together specification-based reasoning and the framework of ant colony optimization (ACO). By this we provide a foundation for distributed reasoning about different properties of the solution space represented by different viewpoint specifications. As a side-effect of reasoning we propagate the information about promising areas in the solution space to the current state. Consequently the system’s decisions can be improved by considering the long term values of certain behavioral trajectories (given a certain situational horizon). We consider this feature to be a contribution to autonomic computing1st IFIP International Conference on Biologically Inspired Cooperative Computing - Biological Inspiration 1Red de Universidades con Carreras en Informática (RedUNCI

Towards distributed reasoning for behavioral optimization

We propose an architecture which supports the behavioral self-optimization of complex systems. In this architecture we bring together specification-based reasoning and the framework of ant colony optimization (ACO). By this we provide a foundation for distributed reasoning about different properties of the solution space represented by different viewpoint specifications. As a side-effect of reasoning we propagate the information about promising areas in the solution space to the current state. Consequently the system’s decisions can be improved by considering the long term values of certain behavioral trajectories (given a certain situational horizon). We consider this feature to be a contribution to autonomic computing1st IFIP International Conference on Biologically Inspired Cooperative Computing - Biological Inspiration 1Red de Universidades con Carreras en Informática (RedUNCI

Speeding up Energy System Models - a Best Practice Guide

Background Energy system models (ESM) are widely used in research and industry to analyze todays and future energy systems and potential pathways for the European energy transition. Current studies address future policy design, analysis of technology pathways and of future energy systems. To address these questions and support the transformation of today’s energy systems, ESM have to increase in complexity to provide valuable quantitative insights for policy makers and industry. Especially when dealing with uncertainty and in integrating large shares of renewable energies, ESM require a detailed implementation of the underlying electricity system. The increased complexity of the models makes the application of ESM more and more difficult, as the models are limited by the available computational power of today’s decentralized workstations. Severe simplifications of the models are common strategies to solve problems in a reasonable amount of time – naturally significantly influencing the validity of results and reliability of the models in general. Solutions for Energy-System Modelling Within BEAM-ME a consortium of researchers from different research fields (system analysis, mathematics, operations research and informatics) develop new strategies to increase the computational performance of energy system models and to transform energy system models for usage on high performance computing clusters. Within the project, an ESM will be applied on two of Germany’s fastest supercomputers. To further demonstrate the general application of named techniques on ESM, a model experiment is implemented as part of the project. Within this experiment up to six energy system models will jointly develop, implement and benchmark speed-up methods. Finally, continually collecting all experiences from the project and the experiment, identified efficient strategies will be documented and general standards for increasing computational performance and for applying ESM to high performance computing will be documented in a best-practice guide

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

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