Harmonic radar tracking reveals that honeybee drones navigate between multiple aerial leks.

Male honeybees (drones) are thought to congregate in large numbers in particular "drone congregation areas" to mate. We used harmonic radar to record the flight paths of individual drones and found that drones favored certain locations within the landscape which were stable over two years. Drones often visit multiple potential lekking sites within a single flight and take shared flight paths between them. Flights between such sites are relatively straight and begin as early as the drone's second flight, indicating familiarity with the sites acquired during initial learning flights. Arriving at congregation areas, drones display convoluted, looping flight patterns. We found a correlation between a drone's distance from the center of each area and its acceleration toward the center, a signature of collective behavior leading to congregation in these areas. Our study reveals the behavior of individual drones as they navigate between and within multiple aerial leks.

Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis.

Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease.

The electronic Rothamsted Archive (e-RA), an online resource for data from the Rothamsted long-term experiments.

The electronic Rothamsted Archive, e-RA (www.era.rothamsted.ac.uk) provides a permanent managed database to both securely store and disseminate data from Rothamsted Research's long-term field experiments (since 1843) and meteorological stations (since 1853). Both historical and contemporary data are made available via this online database which provides the scientific community with access to a unique continuous record of agricultural experiments and weather measured since the mid-19th century. Qualitative information, such as treatment and management practices, plans and soil information, accompanies the data and are made available on the e-RA website. e-RA was released externally to the wider scientific community in 2013 and this paper describes its development, content, curation and the access process for data users. Case studies illustrate the diverse applications of the data, including its original intended purposes and recent unforeseen applications. Usage monitoring demonstrates the data are of increasing interest. Future developments, including adopting FAIR data principles, are proposed as the resource is increasingly recognised as a unique archive of data relevant to sustainable agriculture, agroecology and the environment.

KnetMaps: a BioJS component to visualize biological knowledge networks.

KnetMaps is a BioJS component for the interactive visualization of biological knowledge networks. It is well suited for applications that need to visualise complementary, connected and content-rich data in a single view in order to help users to traverse pathways linking entities of interest, for example to go from genotype to phenotype. KnetMaps loads data in JSON format, visualizes the structure and content of knowledge networks using lightweight JavaScript libraries, and supports interactive touch gestures. KnetMaps uses effective visualization techniques to prevent information overload and to allow researchers to progressively build their knowledge.

Recon2Neo4j: applying graph database technologies for managing comprehensive genome-scale networks.

Summary: The goal of this work is to offer a computational framework for exploring data from the Recon2 human metabolic reconstruction model. Advanced user access features have been developed using the Neo4j graph database technology and this paper describes key features such as efficient management of the network data, examples of the network querying for addressing particular tasks, and how query results are converted back to the Systems Biology Markup Language (SBML) standard format. The Neo4j-based metabolic framework facilitates exploration of highly connected and comprehensive human metabolic data and identification of metabolic subnetworks of interest. A Java-based parser component has been developed to convert query results (available in the JSON format) into SBML and SIF formats in order to facilitate further results exploration, enhancement or network sharing. Availability and Implementation: The Neo4j-based metabolic framework is freely available from: https://diseaseknowledgebase.etriks.org/metabolic/browser/ . The java code files developed for this work are available from the following url: https://github.com/ibalaur/MetabolicFramework . Contact: ibalaur@eisbm.org. Supplementary information: Supplementary data are available at Bioinformatics online.

EpiGeNet: A Graph Database of Interdependencies Between Genetic and Epigenetic Events in Colorectal Cancer.

The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.

Representing and querying disease networks using graph databases.

BACKGROUND: Systems biology experiments generate large volumes of data of multiple modalities and this information presents a challenge for integration due to a mix of complexity together with rich semantics. Here, we describe how graph databases provide a powerful framework for storage, querying and envisioning of biological data. RESULTS: We show how graph databases are well suited for the representation of biological information, which is typically highly connected, semi-structured and unpredictable. We outline an application case that uses the Neo4j graph database for building and querying a prototype network to provide biological context to asthma related genes. CONCLUSIONS: Our study suggests that graph databases provide a flexible solution for the integration of multiple types of biological data and facilitate exploratory data mining to support hypothesis generation.

Ondex Web: web-based visualization and exploration of heterogeneous biological networks.

SUMMARY: Ondex Web is a new web-based implementation of the network visualization and exploration tools from the Ondex data integration platform. New features such as context-sensitive menus and annotation tools provide users with intuitive ways to explore and manipulate the appearance of heterogeneous biological networks. Ondex Web is open source, written in Java and can be easily embedded into Web sites as an applet. Ondex Web supports loading data from a variety of network formats, such as XGMML, NWB, Pajek and OXL. AVAILABILITY AND IMPLEMENTATION: http://ondex.rothamsted.ac.uk/OndexWeb.

Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.

Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge. We study the capsular polysaccharide biosynthetic pathway of the major human gastrointestinal pathogen Campylobacter jejuni. We consider several key steps in the formation of capsular polysaccharide consisting of 15 genes of which 8 have assigned function, and we explore the extent to which functions can be hypothesised for the remaining 7. Two sources of experimental data provide the information for learning-the results of knockout experiments on the genes involved in capsule formation and the absence/presence of capsule genes in a multitude of strains of different serotypes. The machine learning uses the pathway structure as background knowledge. We propose assignments of specific genes to five previously unassigned reaction steps. For four of these steps, there was an unambiguous optimal assignment of gene to reaction, and to the fifth, there were three candidate genes. Several of these assignments were consistent with additional experimental results. We therefore show that the logic-based methodology provides a robust strategy to integrate results from different experimental approaches and propose hypotheses for the behaviour of a biological system.

InterStoreDB: a generic integration resource for genetic and genomic data.

Associating phenotypic traits and quantitative trait loci (QTL) to causative regions of the underlying genome is a key goal in agricultural research. InterStoreDB is a suite of integrated databases designed to assist in this process. The individual databases are species independent and generic in design, providing access to curated datasets relating to plant populations, phenotypic traits, genetic maps, marker loci and QTL, with links to functional gene annotation and genomic sequence data. Each component database provides access to associated metadata, including data provenance and parameters used in analyses, thus providing users with information to evaluate the relative worth of any associations identified. The databases include CropStoreDB, for management of population, genetic map, QTL and trait measurement data, SeqStoreDB for sequence-related data and AlignStoreDB, which stores sequence alignment information, and allows navigation between genetic and genomic datasets. Genetic maps are visualized and compared using the CMAP tool, and functional annotation from sequenced genomes is provided via an EnsEMBL-based genome browser. This framework facilitates navigation of the multiple biological domains involved in genetics and genomics research in a transparent manner within a single portal. We demonstrate the value of InterStoreDB as a tool for Brassica research. InterStoreDB is available from: http://www.interstoredb.org.

AIGO: towards a unified framework for the analysis and the inter-comparison of GO functional annotations.

BACKGROUND: In response to the rapid growth of available genome sequences, efforts have been made to develop automatic inference methods to functionally characterize them. Pipelines that infer functional annotation are now routinely used to produce new annotations at a genome scale and for a broad variety of species. These pipelines differ widely in their inference algorithms, confidence thresholds and data sources for reasoning. This heterogeneity makes a comparison of the relative merits of each approach extremely complex. The evaluation of the quality of the resultant annotations is also challenging given there is often no existing gold-standard against which to evaluate precision and recall. RESULTS: In this paper, we present a pragmatic approach to the study of functional annotations. An ensemble of 12 metrics, describing various aspects of functional annotations, is defined and implemented in a unified framework, which facilitates their systematic analysis and inter-comparison. The use of this framework is demonstrated on three illustrative examples: analysing the outputs of state-of-the-art inference pipelines, comparing electronic versus manual annotation methods, and monitoring the evolution of publicly available functional annotations. The framework is part of the AIGO library (http://code.google.com/p/aigo) for the Analysis and the Inter-comparison of the products of Gene Ontology (GO) annotation pipelines. The AIGO library also provides functionalities to easily load, analyse, manipulate and compare functional annotations and also to plot and export the results of the analysis in various formats. CONCLUSIONS: This work is a step toward developing a unified framework for the systematic study of GO functional annotations. This framework has been designed so that new metrics on GO functional annotations can be added in a very straightforward way.

Assessing the functional coherence of modules found in multiple-evidence networks from Arabidopsis.

BACKGROUND: Combining multiple evidence-types from different information sources has the potential to reveal new relationships in biological systems. The integrated information can be represented as a relationship network, and clustering the network can suggest possible functional modules. The value of such modules for gaining insight into the underlying biological processes depends on their functional coherence. The challenges that we wish to address are to define and quantify the functional coherence of modules in relationship networks, so that they can be used to infer function of as yet unannotated proteins, to discover previously unknown roles of proteins in diseases as well as for better understanding of the regulation and interrelationship between different elements of complex biological systems. RESULTS: We have defined the functional coherence of modules with respect to the Gene Ontology (GO) by considering two complementary aspects: (i) the fragmentation of the GO functional categories into the different modules and (ii) the most representative functions of the modules. We have proposed a set of metrics to evaluate these two aspects and demonstrated their utility in Arabidopsis thaliana. We selected 2355 proteins for which experimentally established protein-protein interaction (PPI) data were available. From these we have constructed five relationship networks, four based on single types of data: PPI, co-expression, co-occurrence of protein names in scientific literature abstracts and sequence similarity and a fifth one combining these four evidence types. The ability of these networks to suggest biologically meaningful grouping of proteins was explored by applying Markov clustering and then by measuring the functional coherence of the clusters. CONCLUSIONS: Relationship networks integrating multiple evidence-types are biologically informative and allow more proteins to be assigned to a putative functional module. Using additional evidence types concentrates the functional annotations in a smaller number of modules without unduly compromising their consistency. These results indicate that integration of more data sources improves the ability to uncover functional association between proteins, both by allowing more proteins to be linked and producing a network where modular structure more closely reflects the hierarchy in the gene ontology.

Enhancing data integration with text analysis to find proteins implicated in plant stress response.

High throughput genomic studies can identify large numbers of potential candidate genes, which must be interpreted and filtered by investigators to select the best ones for further analysis. Prioritization is generally based on evidence that supports the role of a gene product in the biological process being investigated. The two most important bodies of information providing such evidence are bioinformatics databases and the scientific literature. In this paper we present an extension to the Ondex data integration framework that uses text mining techniques over Medline abstracts as a method for accessing both these bodies of evidence in a consistent way. In an example use case, we apply our method to create a knowledge base of Arabidopsis proteins implicated in plant stress response and use various scoring metrics to identify key protein-stress associations. In conclusion, we show that the additional text mining features are able to highlight proteins using the scientific literature that would not have been seen using data integration alone. Ondex is an open-source software project and can be downloaded, together with the text mining features described here, from www.ondex.org.

Wheat Estimated Transcript Server (WhETS): a tool to provide best estimate of hexaploid wheat transcript sequence.

Wheat biologists face particular problems because of the lack of genomic sequence and the three homoeologous genomes which give rise to three very similar forms for many transcripts. However, over 1.3 million available public-domain Triticeae ESTs (of which approximately 850,000 are wheat) and the full rice genomic sequence can be used to estimate likely transcript sequences present in any wheat cDNA sample to which PCR primers may then be designed. Wheat Estimated Transcript Server (WhETS) is designed to do this in a convenient form, and to provide information on the number of matching EST and high quality cDNA (hq-cDNA) sequences, tissue distribution and likely intron position inferred from rice. Triticeae EST and hq-cDNA sequences are mapped onto rice loci and stored in a database. The user selects a rice locus (directly or via Arabidopsis) and the matching Triticeae sequences are assembled according to user-defined filter and stringency settings. Assembly is achieved initially with the CAP3 program and then with a single nucleotide polymorphism (SNP)-analysis algorithm designed to separate homoeologues. Alignment of the resulting contigs and singlets against the rice template sequence is then displayed. Sequences and assembly details are available for download in fasta and ace formats, respectively. WhETS is accessible at http://www4.rothamsted.bbsrc.ac.uk/whets.

SNP cherry picker: maximizing the chance of finding an association with a disease SNP.

UNLABELLED: The high cost of genotyping single nucleotide polymorphisms (SNPs) generally prohibits the systematic mapping of entire genetic linkage regions in order to find the polymorphisms associated with increased risk of disease. In practice, SNPs are selected at approximately equal spacing across the linkage region to try to locate a SNP lying in the haplotype block of the disease SNP. The size of the haplotype block may not be known, however, and SNPs taken from public domain sources may not in fact be polymorphic. Our program will choose a subset of the SNPs in a linkage region so as to maximize the expected proportion of the sequence that lies within a given distance of a real SNP. AVAILABILITY: The software is available, free of charge, for academic use on request from the authors. SUPPLEMENTARY INFORMATION: www.oxagen.co.uk

Pedstrip: extracting a maximal subset of available, unrelated individuals from a pedigree.

UNLABELLED: Certain types of genetic analysis are simplified by assembling a collection of unrelated individuals, e.g. case-control experiments. If a family study is being performed then it will be necessary to extract subsets of unrelated, available individuals from pedigress. Our program provides an optimal method for performing this task. AVAILABILITY: The software is available, free of charge, on request from Oxagen Ltd. SUPPLEMENTARY INFORMATION: http://www.oxagen.co.uk