WHITE PAPER: AN OVERVIEW OF CONCEPTUAL FRAMEWORKS, ANALYTICAL APPROACHES AND RESEARCH QUESTIONS IN THE FOOD-ENERGY-WATER NEXUS

The food-energy-water (FEW) nexus is increasingly emphasized and prioritized as a framework for research, technology, and policy to deal with complex socio-environmental problems. Producing food in sufficient quantity and of sufficient quality, ensuring enough but not too much water, and generating energy, all to meet human needs and desires, requires an understanding of how those goals complement or counteract one another in specific places and through specific processes. FEW nexus research focuses on understanding the interconnections among each system, in order to provide a more complete picture about the causes and consequences of changes within and across aspects of those systems. This paper synthesizes the current state of thinking and research in FEW nexus field. We first overview the systems underpinnings of the FEW nexus as a conceptual framework, and identify the assumptions, similarities and contrasts among the most cited models from current literature. Several analytical approaches – coupled systems, ecosystem services, flows and risk analysis – are emerging as key tools for conducting interdisciplinary FEW nexus research, and we identify their conceptual connections to systems thinking broadly as well as the specific assumptions that each make about the relationships among systems. Finally, based on expert consultations and assessment of current data availability, we highlight several topical areas of contemporary relevance for FEW nexus research at various scales. Characterizing the conceptual, analytical and empirical similarities and distinctions among approaches to FEW nexus research with a starting point for identifying innovative research questions and approaches.This work was supported by the National Socio-Environmental Synthesis Center (SESYNC), which is funded by National Science Foundation Grant # DBI-1052875

Reserves and trade jointly determine exposure to food supply shocks

While a growing proportion of global food consumption is obtained through international trade, there is an ongoing debate on whether this increased reliance on trade benefits or hinders food security, and specifically, the ability of global food systems to absorb shocks due to local or regional losses of production. This paper introduces a model that simulates the short-term response to a food supply shock originating in a single country, which is partly absorbed through decreases in domestic reserves and consumption, and partly transmitted through the adjustment of trade flows. By applying the model to publicly-available data for the cereals commodity group over a 17 year period, we find that differential outcomes of supply shocks simulated through this time period are driven not only by the intensification of trade, but as importantly by changes in the distribution of reserves. Our analysis also identifies countries where trade dependency may accentuate the risk of food shortages from foreign production shocks; such risk could be reduced by increasing domestic reserves or importing food from a diversity of suppliers that possess their own reserves. This simulation-based model provides a framework to study the short-term, nonlinear and out-of-equilibrium response of trade networks to supply shocks, and could be applied to specific scenarios of environmental or economic perturbations

From meta-studies to modeling: Using synthesis knowledge to build broadly applicable process-based land change models

International audienceThis paper explores how meta-studies can support the development of process-based land change models (LCMs) that can be applied across locations and scales. We describe a multi-step framework for model development and provide descriptions and examples of how meta-studies can be used in each step. We conclude that meta-studies best support the conceptualization and experimentation phases of the model development cycle, but cannot typically provide full model parameterizations. Moreover, meta-studies are particularly useful for developing agent-based LCMs that can be applied across a wide range of contexts, locations, and/or scales, because meta-studies provide both quantitative and qualitativedata needed to derive agent behaviors more readily than from case study or aggregate data sources alone. Recent land change synthesis studies provide sufficient topical breadth and depth to support the development of broadly applicable process-based LCMs, as well as the potential to accelerate the production of generalized knowledge through model-driven synthesis

Beyond land cover change: Towards a new generation of Land Use Models

Land use models play an important role in exploring future land change dynamics and are instrumental to support the integration of knowledge in land system science. However, only modest progress has been made in achieving these aims due to insufficient model evaluation and limited representation of the underlying socio-ecological processes. We discuss how land use models can better represent multi-scalar dynamics, human agency and demand-supply relations, and how we can achieve learning from model evaluation. By addressing these issues we outline pathways towards a new generation of land use models that allow not only the assessment of future land cover pattern changes, but also stimulate envisioning future land use by society to support debate on sustainability solutions and help design alternative solutions

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

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

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

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