The Reactome pathway knowledgebase.

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.

Gramene 2013: comparative plant genomics resources.

Gramene (http://www.gramene.org) is a curated online resource for comparative functional genomics in crops and model plant species, currently hosting 27 fully and 10 partially sequenced reference genomes in its build number 38. Its strength derives from the application of a phylogenetic framework for genome comparison and the use of ontologies to integrate structural and functional annotation data. Whole-genome alignments complemented by phylogenetic gene family trees help infer syntenic and orthologous relationships. Genetic variation data, sequences and genome mappings available for 10 species, including Arabidopsis, rice and maize, help infer putative variant effects on genes and transcripts. The pathways section also hosts 10 species-specific metabolic pathways databases developed in-house or by our collaborators using Pathway Tools software, which facilitates searches for pathway, reaction and metabolite annotations, and allows analyses of user-defined expression datasets. Recently, we released a Plant Reactome portal featuring 133 curated rice pathways. This portal will be expanded for Arabidopsis, maize and other plant species. We continue to provide genetic and QTL maps and marker datasets developed by crop researchers. The project provides a unique community platform to support scientific research in plant genomics including studies in evolution, genetics, plant breeding, molecular biology, biochemistry and systems biology.

Impacts of tourism hotspots on vegetation communities show a higher potential for self-propagation along roads than hiking trails.

Vegetation communities along recreational tracks may suffer from substantial edge-effects through the impacts of trampling, modified environmental conditions and competition with species that benefit from disturbance. We assessed impacts on trackside vegetation by comparing high and low usage tourism sites at a 1-10 m distance from recreational tracks in a popular arid-lands tourism destination in South Australia. The central aim was quantification of the strengths and spatial extent of tourism impacts along recreational tracks with a qualitative comparison of roads and trails. Track-distance gradients were most prevalent at high usage sites. There, species community composition was altered, total plant cover decreased, non-native species cover increased, plant diversity increased or decreased (depending on the distance) and soil compaction increased towards recreational tracks. Roadside effects were greater and more pervasive than trailside effects. Further, plant diversity did not continuously increase towards the road verge as it did along trails but dropped sharply in the immediate road shoulder which indicated high disturbance conditions that few species were able to tolerate. To our knowledge, we are the first to demonstrate that the access mode to a recreation site influences the potential of certain impacts, such as the increase of non-native species, to self-perpetuate from their points of introduction to disjointed sites with a predisposition to disturbance. Due to this propulsion of impacts, the overall spatial extent of roadside impacts was far greater than initially apparent from assessments at the road verge. We discuss possible means of mitigating these impacts.

Reactome: a database of reactions, pathways and biological processes.

Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice.

Vegetation moderates impacts of tourism usage on bird communities along roads and hiking trails.

Bird communities inhabiting ecosystems adjacent to recreational tracks may be adversely affected by disturbance from passing tourism traffic, vehicle-related mortality, habitat alteration and modified biotic relationships such as the increase of strong competitors. This study investigated the effects of tourist usage of roads vs. hiking trails on bird communities in gorges of the Flinders Ranges, a popular South Australian tourist destination in the arid-lands. High tourist usage along roads decreased the individual abundance and species richness of birds relative to low usage trails. The decrease in species richness, though less pronounced, also occurred at high-usage sites along trails. Changes in the species response to recreational disturbance/impacts varied depending on the ecology of the species. Bigger, more competitive birds with a generalist diet were overrepresented at high-usage sites along roads and trails. Species using microhabitats in lower vegetation layers were more sensitive. However, structural and floristic complexity of vegetation was a more important factor influencing bird abundance than tourist usage. Sites with a better developed shrub and tree layer sustained higher species abundance and richer communities. Importantly, vegetation qualities moderated the negative effect of high usage on the individual abundance of birds along roads, to the extent that such an effect was absent at sites with the best developed shrub and tree layer. To protect avifauna along recreational tracks in arid-lands gorges, we recommend the closure of some gorges or sections for vehicle or any access. Further, open space particularly for camping needs to be minimized as it creates areas of high tourist usage with modified habitat that provides birds with little buffer from disturbance.

Reactome knowledgebase of human biological pathways and processes.

Reactome (http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2975 human proteins, 2907 reactions and 4455 literature citations. A new entity-level pathway viewer and improved search and data mining tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. Reactome has increased its utility to the model organism communities with improved orthology prediction methods allowing pathway inference for 22 species and through collaborations to create manually curated Reactome pathway datasets for species including Arabidopsis, Oryza sativa (rice), Drosophila and Gallus gallus (chicken). Reactome's data content and software can all be freely used and redistributed under open source terms.

The Perils of Being Populous: Control and Conservation of Abundant Kangaroo Species.

Australia's first people managed landscapes for kangaroo species as important elements of their diet, accoutrements and ceremony. This developed and persisted for about 65,000 years. The second wave of colonists from the United Kingdom, Ireland and many subsequent countries introduced familiar domesticated livestock and they have imposed their agricultural practices on the same landscapes since 1788. This heralded an ongoing era of management of kangaroos that are perceived as competitors to livestock and unwanted consumers of crops. Even so, a kangaroo image remains the iconic identifier of Australia. Kangaroo management is shrouded in dogma and propaganda and creates a tension along a loose rural-city divide. This divide is further dissected by the promotion of the consumption of kangaroo products as an ecological good marred by valid concerns about hygiene and animal welfare. In the last decade, the fervour to suppress and micro-manage populations of some kangaroo species has mounted. This includes suppression within protected areas that have generally been considered as safe havens. This review explores these tensions between the conservation of iconic and yet abundant wildlife, and conflict with people and the various interfaces at which they meet kangaroos.

MAGICPL: A Generic Process Description Language for Distributed Pseudonymization Scenarios.

OBJECTIVES: Pseudonymization is an important aspect of projects dealing with sensitive patient data. Most projects build their own specialized, hard-coded, solutions. However, these overlap in many aspects of their functionality. As any re-implementation binds resources, we would like to propose a solution that facilitates and encourages the reuse of existing components. METHODS: We analyzed already-established data protection concepts to gain an insight into their common features and the ways in which their components were linked together. We found that we could represent these pseudonymization processes with a simple descriptive language, which we have called MAGICPL, plus a relatively small set of components. We designed MAGICPL as an XML-based language, to make it human-readable and accessible to nonprogrammers. Additionally, a prototype implementation of the components was written in Java. MAGICPL makes it possible to reference the components using their class names, making it easy to extend or exchange the component set. Furthermore, there is a simple HTTP application programming interface (API) that runs the tasks and allows other systems to communicate with the pseudonymization process. RESULTS: MAGICPL has been used in at least three projects, including the re-implementation of the pseudonymization process of the German Cancer Consortium, clinical data flows in a large-scale translational research network (National Network Genomic Medicine), and for our own institute's pseudonymization service. CONCLUSIONS: Putting our solution into productive use at both our own institute and at our partner sites facilitated a reduction in the time and effort required to build pseudonymization pipelines in medical research.

Oncology on FHIR: A Data Model for Distributed Cancer Research.

In the field of oncology, a close integration of cancer research and patient care is indispensable. Although an exchange of data between health care providers and other institutions such as cancer registries has already been established in Germany, it does not take advantage of internationally coordinated health data standards. Translational cancer research would also benefit from such standards in the context of secondary data use. This paper employs use cases from the German Cancer Consortium (DKTK) to show how this gap can be closed using a harmonised FHIR-based data model, and how to apply it to an existing federated data platform.

Contradiction and Complacency Shape Attitudes towards the Toll of Roads on Wildlife.

Most people in the world now live in cities. Urbanisation simultaneously isolates people from nature and contributes to biodiversity decline. As cities expand, suburban development and the road infrastructure to support them widens their impact on wildlife. Even so, urban communities, especially those on the peri-urban fringe, endeavour to support biodiversity through wildlife friendly gardens, green spaces and corridors, and conservation estates. On one hand, many who live on city fringes do so because they enjoy proximity to nature, however, the ever increasing intrusion of roads leads to conflict with wildlife. Trauma (usually fatal) to wildlife and (usually emotional and financial) to people ensues. Exposure to this trauma, therefore, should inform attitudes towards wildlife vehicle collisions (WVC) and be linked to willingness to reduce risk of further WVC. While there is good anecdotal evidence for this response, competing priorities and better understanding of the likelihood of human injury or fatalities, as opposed to wildlife fatalities, may confound this trend. In this paper we sought to explore this relationship with a quantitative study of driver behaviour and attitudes to WVC from a cohort of residents and visitors who drive through a peri-urban reserve (Royal National Park) on the outskirts of Sydney, Australia. We distributed a self-reporting questionnaire and received responses from 105 local residents and 51 visitors to small townships accessed by roads through the national park. We sought the respondents' exposure to WVC, their evasive actions in an impending WVC, their attitudes to wildlife fatalities, their strategies to reduce the risk of WVC, and their willingness to adopt new ameliorative measures. The results were partitioned by driver demographics and residency. Residents were generally well informed about mitigation strategies but exposure led to a decrease in viewing WVC as very serious. In addition, despite most respondents stating they routinely drive slower when collision risk is high (at dusk and dawn), our assessment of driving trends via traffic speeds suggested this sentiment was not generally adhered to. Thus we unveil some of the complexities in tackling driver's willingness to act on reducing risk of WVC, particularly when risk of human trauma is low.

Case study: data management strategies in an integrated pathway tool.

This paper describes the development strategies for an integrated tool to support scientists in the creative exploration of data relating to biochemical pathways. The multiple user groups, diverse functionalities, and many types and sources of data demanded a flexible yet coherent approach. This paper summarises the software requirements and the implied modules and functions, and focuses on the design decisions relevant to the representation, management and flow of data. Finally, several case studies in the use of the software are described and evaluated, and recommendations are made for future work.

Building models using Reactome pathways as templates.

The first steps of building a new model can be very time-consuming, involving consulting many research papers and then assembling a plausible network of reactions. In this chapter, tools for speeding up this process will be discussed. Reactome is a database containing extensive coverage of pathways in Homo sapiens and numerous reference species. It offers researchers wishing to create new models from scratch various tools for extracting the relevant reactions, complete with layout information. In this chapter, two use cases will be described, in which a modeller provides certain essential pieces of information and Reactome automatically constructs the basic models and then dumps them in SBML-ML format.

Annotating cancer variants and anti-cancer therapeutics in reactome.

Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of "cancer" pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics.

Critical amino acid residues in proteins: a BioMart integration of Reactome protein annotations with PRIDE mass spectrometry data and COSMIC somatic mutations.

The reversible phosphorylation of serine, threonine and tyrosine hydroxyl groups is an especially prominent form of post-translational modification (PTM) of proteins. It plays critical roles in the regulation of diverse processes, and mutations that directly or indirectly affect these phosphorylation events have been associated with many cancers and other pathologies. Here, we describe the development of a new BioMart tool that gathers data from three different biological resources to provide the user with an integrated view of phosphorylation events associated with a human protein of interest, the complexes of which the protein (modified or not) is a part, the reactions in which the protein and its complexes participate and the somatic mutations that might be expected to perturb those functions. The three resources used are the Reactome, PRIDE and COSMIC databases. The Reactome knowledgebase contains annotations of phosphorylated human proteins linked to the reactions in which they are phosphorylated and dephosphorylated, to the complexes of which they are parts and to the reactions in which the phosphorylated proteins participate as substrates, catalysts and regulators. The PRIDE database holds extensive mass spectrometry data from which protein phosphorylation patterns can be inferred, and the COSMIC database holds records of somatic mutations found in human cancer cells. This tool supports both flexible, user-specified queries and standard ('canned') queries to retrieve frequently used combinations of data for user-specified proteins and reactions. We demonstrate using the Wnt signaling pathway and the human c-SRC protein how the tool can be used to place somatic mutation data into a functional perspective by changing critical residues involved in pathway modulation, and where available, check for mass spectrometry evidence in PRIDE supporting identification of the critical residue.

The Reactome BioMart.

Reactome is an open source, expert-authored, manually curated and peer-reviewed database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Reactome BioMart provides biologists and bioinformaticians with a single web interface for performing simple or elaborate queries of the Reactome database, aggregating data from different sources and providing an opportunity to integrate experimental and computational results with information relating to biological pathways. Database URL: http://www.reactome.org.

BioMart Central Portal: an open database network for the biological community.

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities.

Reactome: a knowledge base of biologic pathways and processes.

Reactome http://www.reactome.org, an online curated resource for human pathway data, provides infrastructure for computation across the biologic reaction network. We use Reactome to infer equivalent reactions in multiple nonhuman species, and present data on the reliability of these inferred reactions for the distantly related eukaryote Saccharomyces cerevisiae. Finally, we describe the use of Reactome both as a learning resource and as a computational tool to aid in the interpretation of microarrays and similar large-scale datasets.

Domestic pigeons (Columba livia) discriminate between photographs of male and female pigeons.

We investigated whether pigeons are able to discriminate color photographs of male and female pigeons, using a categorical discrimination procedure. In Experiments 1 and 2B, 10 out of 14 pigeons learned the discrimination. Of these, 5 pigeons showed transfer to novel stimuli, demonstrating the categorical nature of the trained discrimination. Experiment 3 showed that the discriminative behavior was based primarily on the body, as opposed to the head and the neck region. In 1 out of 3 pigeons, the discriminative behavior was maintained by the black-and-white photographs. The results suggest that some pigeons have the ability to discriminate the sex of conspecifics without behavioral cues.

Domestic pigeons (Columba livia) discriminate between photographs of individual pigeons.

In two experiments, we examined the discrimination of photographs of individual pigeons by pigeons, using go/no-go discrimination procedures. In Experiments 1A and 1B, the pigeons were trained to discriminate 4 photographs of one pigeon from those of a number of pigeons. The subjects learned the discrimination, but their discriminative behavior did not transfer to new photographs taken from novel perspectives. When the pigeons were trained to discriminate between 20 photographs of five pigeons taken from four perspectives as the S+ and 20 photographs of five different pigeons as the S-, the subjects learned the discrimination, and this discriminative behavior partially transferred to new photographs taken from novel perspectives (Experiments 2A-2C). The results suggest that pigeons are able to discriminate among conspecific individuals, using stationary visual cues. This strengthens the assumption in evolutionary theory that animals can discriminate among individuals and encourages further investigation as to how this ability is used in various behaviors of animals.

The relationship between serum albumin and hydration status in hemodialysis patients.

OBJECTIVE: A decreased serum albumin level predicts poor survival in end-stage renal failure. Hypoalbuminemia is multifactorial and related to poor nutrition, inflammation, and comorbid disease. Overhydration is also common in renal replacement therapy patients, and hemodilution may also contribute to a low serum albumin level. DESIGN: Crosssectional observational study. SETTING: Outpatient hemodialysis unit of a district general hospital. SUBJECTS: We investigated the relationship of serum albumin to C-reactive protein (CRP) and hydration state in 49 unselected hemodialysis patients (28 men). METHODS: Patients were assessed predialysis and postdialysis at their clinical dry weight. Extracellular fluid volume (Vecf) and total body water (Vtbw) were estimated by whole-body bioelectric impedance. Vecf was expressed as a percentage of Vtbw (Vecf%Vtbw). Predialysis CRP, predialysis and postdialysis serum albumin, and body weight were measured. Normalized protein catabolic rate (nPCR) and KT/V urea were calculated. RESULTS: Predialysis and postdialysis serum albumin levels were 36.9 g/L (95% CI, 35.7 and 38.1) and 41.4 g/L (95% CI, 39.7 and 43.3), respectively (P <.0001). Mean weight change was 2.0 +/- 1.2 kg. Predialysis and postdialysis serum albumin levels were negatively correlated with CRP (before: r = -0.393, P <.005; after: r = -0.445, P =.001) and positively with nPCR (before: r = 0.336, P =.018; after: r = 0.353, P =.013). Predialysis serum albumin level correlated with predialysis Vecf%Vtbw (r = -0.384, P =.006) and postdialysis serum albumin level with postdialysis Vecf%Vtbw (r = -0.654, P <.0001). In multivariate analysis, predialysis albumin was dependent on nPCR (P =.04), CRP (P <.0001), and predialysis Vecf%Vtbw (P =.002), and postdialysis albumin was dependent on nPCR (P =.01), CRP (P =.002), and postdialysis Vecf%Vtbw (both P <.0001). The increase in albumin was strongly correlated with both change in actual weight (r = -0.651, P <.0001) and change in Vecf%Vtbw (r = -0.684, P <.0001). CONCLUSION: In unselected hemodialysis patients, serum albumin level is dependent on nPCR, CRP, and extracellular fluid volume. This relationship persists after dialysis, suggesting that many patients remain fluid overloaded at their postdialysis dry weight.