Analysis and visualisation of RDF resources in Ondex

An increasing number of biomedical resources provide their information on the Semantic Web and this creates the basis for a distributed knowledge base which has the potential to advance biomedical research [1]. This potential, however, cannot be realized until researchers from the life sciences can interact with information in the Semantic Web. In particular, there is a need for tools that provide data reduction, visualization and interactive analysis capabilities.
Ondex is a data integration and visualization platform developed to support Systems Biology Research [2]. At its core is a data model based on two main principles: first, all information can be represented as a graph and, second, all elements of the graph can be annotated with ontologies. This data model conforms to the Semantic Web framework, in particular to RDF, and therefore Ondex is ideally positioned as a platform that can exploit the semantic web. 
The Ondex system offers a range of features and analysis methods of potential value to semantic web users, including:
-	An interactive graph visualization interface (Ondex user client), which provides data reduction and representation methods that leverage the ontological annotation.
-	A suite of importers from a variety of data sources to Ondex (http://ondex.org/formats.html)
-	A collection of plug-ins which implement graph analysis, graph transformation and graph-matching functions.
-	An integration toolkit (Ondex Integrator) which allows users to compose workflows from these modular components
-	In addition, all importers and plug-ins are available as web-services which can be integrated in other tools, as for instance Taverna [3].
The developments that will be presented in this demo have made this functionality interoperable with the Semantic Web framework. In particular we have developed an interactive importer, based on SPARQL that allows the query-driven construction of datasets which brings together information from different RDF data resources into Ondex.
These datasets can then be further refined, analysed and annotated both interactively using the Ondex user client and via user-defined workflows. The results of these analyses can be exported in RDF, which can be used to enrich existent knowledge bases, or to provide application-specific views of the data. Both importer and exporter only focus on a subset of the Ondex and RDF data models, which are shared between these two data representations [4].
In this demo we will show how Ondex can be used to query, analyse and visualize Semantic Web knowledge bases. In particular we will present real use cases focused, but not limited to, resources relevant to plant biology. 
We believe that Ondex can be a valid contribution to the adoption of the Semantic Web in Systems Biology research and in biomedical investigation more generally. We welcome feedback on our current import/export prototype and suggestions for the advancement of Ondex for the Semantic Web.

References

1.	Ruttenberg, A. et. al.: Advancing translational research with the Semantic Web, BMC Bioinformatics, 8 (Suppl. 3): S2 (2007).
2.	Köhler, J., Baumbach, J., Taubert, J., Specht, M., Skusa, A., Ruegg, A., Rawlings, C., Verrier, P., Philippi, S.: Graph-based analysis and visualization of experimental results with Ondex. Bioinformatics 22 (11):1383-1390 (2006).
3.	Rawlings, C.: Semantic Data Integration for Systems Biology Research, Technology Track at ISMB’09, http://www.iscb.org/uploaded/css/36/11846.pdf (2009).
4.	Splendiani, A. et. al.: Ondex semantic definition, (Web document) http://ondex.svn.sourceforge.net/viewvc/ondex/trunk/doc/semantics/ (2009).
&#xa

Towards linked open gene mutations data

<p>Abstract</p> <p>Background</p> <p>With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework.</p> <p>In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data.</p> <p>Methods</p> <p>A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest.</p> <p>Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite.</p> <p>Results</p> <p>We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application.</p> <p>Conclusions</p> <p>This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development.</p> <p>The publication of variation information as Linked Data opens new perspectives: the exploitation of SPARQL searches on mutation data and other biological databases may support data retrieval which is presently not possible. Moreover, reasoning on integrated variation data may support discoveries towards personalized medicine.</p

Phylogenetic and biogeographic history of brook lampreys (Lampetra: Petromyzontidae) in the river basins of the Adriatic Sea based on DNA barcode data.

The Adriatic brook lamprey, Lampetra zanandreai Vladykov 1955, was described from northeastern Italy. Its distribution is thought to include left tributaries of the River Po and the river basins of the Adriatic Sea from the River Po to the River Isonzo/Soča in Italy, Switzerland and Slovenia. It also shows a geographically isolated distribution in the Potenza River on the Adriatic slope in Central Italy. Lampetra from the Neretva River system in Croatia and Bosnia and Herzegovina and the Morača River system in Montenegro that were previously identified as L. zanandreai were recently described as a new species Lampetra soljani Tutman, Freyhof, Dulčić, Glamuzina & Geiger 2017 based on morphological data and a genetic distance between the two species of roughly 2.5% in the DNA barcoding gene cytochrome oxidase I (COI). Since DNA barcodes for L. zanandreai are only available for one population from the upper Po River in northwestern Italy, we generated additional COI nucleotide sequence data of this species from Switzerland, northeastern and central Italy comprising near topotypic material and obtained GenBank sequences of the species from Slovenia to better assess the evolutionary history of the two brook lamprey species in the river basins of the Adriatic Sea. Our data show a low sequence divergence of <1% between L. zanandreai from Switzerland, northeastern and central Italy and Slovenia and the Balkan species L. soljani. However, members of the population previously identified as 'L. zanandreai' from northwest Italy are genetically highly divergent from those of L. zanandreai and likely belong to an undescribed species, L. sp. 'upper Po'. The presence of a unique and highly divergent brook lamprey lineage in the upper Po River suggests that L. zanandreai and Lampetra sp. 'upper Po' may have evolved in separate paleo drainages during the formation of the modern Po Valley subsequent to marine inundations in the Pliocene

The stuffed crocodile of "Castel Nuovo" in Naples (Italy): new insights from ancient DNA and radiocarbon

In the present study, a stuffed crocodile displayed for centuries at the "Castel Nuovo" (New Castle) in Naples was radiocarbon dated and examined using ancient DNA analysis. The specimen was classified as Crocodylus niloticus based on its large body size and the mitochondrial DNA haplotype obtained, already described for a living population in Lake Nasser (Egypt). Radiocarbon analysis indicated an age of 585 ± 40 14C year BP, which coincides with the end of the Middle Ages. These results are commented in the light of Medieval religious symbolism and ancient legends which link the crocodile to the history of Naples during the mid-fifteenth century. The data obtained seem to confirm the explanation found in an old guidebook to Naples, according to which the stuffed crocodile was offered by a soldier returning from Egypt as an ex-voto to the image of the "Madonna del Parto" in the chapel of the castle. In addition, the radiocarbon dating shows that the individual analysed could be the oldest taxidermied vertebrate in Europe

Biomedical semantics in the Semantic Web

The Semantic Web offers an ideal platform for representing and linking biomedical information, which is a prerequisite for the development and application of analytical tools to address problems in data-intensive areas such as systems biology and translational medicine. As for any new paradigm, the adoption of the Semantic Web offers opportunities and poses questions and challenges to the life sciences scientific community: which technologies in the Semantic Web stack will be more beneficial for the life sciences? Is biomedical information too complex to benefit from simple interlinked representations? What are the implications of adopting a new paradigm for knowledge representation? What are the incentives for the adoption of the Semantic Web, and who are the facilitators? Is there going to be a Semantic Web revolution in the life sciences

Pug-Headedness Anomaly in a Wild and Isolated Population of Native Mediterranean Trout Salmo trutta L., 1758 Complex (Osteichthyes: Salmonidae)

Skeletal anomalies are commonplace among farmed fish. The pug-headedness anomaly is an osteological condition that results in the deformation of the maxilla, pre-maxilla, and infraorbital bones. Here, we report the first record of pug-headedness in an isolated population of the critically endangered native Mediterranean trout Salmo trutta L., 1758 complex from Sardinia, Italy. Fin clips were collected for the molecular analyses (D-loop, LDH-C1* locus. and 11 microsatellites). A jaw index (JI) was used to classify jaw deformities. Ratios between the values of morphometric measurements of the head and body length were calculated and plotted against values of body length to identify the ratios that best discriminated between malformed and normal trout. Haplotypes belonging to the AD lineage and the genotype LDH-C1*100/100 were observed in all samples, suggesting high genetic integrity of the population. The analysis of 11 microsatellites revealed that observed heterozygosity was similar to the expected one, suggesting the absence of inbreeding or outbreeding depression. The frequency of occurrence of pug-headedness was 12.5% (two out of 16). One specimen had a strongly blunted forehead and an abnormally short upper jaw, while another had a slightly anomaly asymmetrical jaw. Although sample size was limited, variation in environmental factors during larval development seemed to be the most likely factors to trigger the deformities

A power law global error model for the identification of differentially expressed genes in microarray data

BACKGROUND: High-density oligonucleotide microarray technology enables the discovery of genes that are transcriptionally modulated in different biological samples due to physiology, disease or intervention. Methods for the identification of these so-called "differentially expressed genes" (DEG) would largely benefit from a deeper knowledge of the intrinsic measurement variability. Though it is clear that variance of repeated measures is highly dependent on the average expression level of a given gene, there is still a lack of consensus on how signal reproducibility is linked to signal intensity. The aim of this study was to empirically model the variance versus mean dependence in microarray data to improve the performance of existing methods for identifying DEG. RESULTS: In the present work we used data generated by our lab as well as publicly available data sets to show that dispersion of repeated measures depends on location of the measures themselves following a power law. This enables us to construct a power law global error model (PLGEM) that is applicable to various Affymetrix GeneChip data sets. A new DEG identification method is therefore proposed, consisting of a statistic designed to make explicit use of model-derived measurement spread estimates and a resampling-based hypothesis testing algorithm. CONCLUSIONS: The new method provides a control of the false positive rate, a good sensitivity vs. specificity trade-off and consistent results with varying number of replicates and even using single samples

Mediterranean swordfish (Xiphias gladius Linnaeus, 1758) population structure revealed by microsatellite DNA: genetic diversity masked by population mixing in shared areas

Background The Mediterranean swordfish stock is overfished and considered not correctly managed. Elucidating the patterns of the Mediterranean swordfish population structure constitutes an essential prerequisite for effective management of this fishery resource. To date, few studies have investigated intra-Mediterranean swordfish population structure, and their conclusions are controversial. Methods A panel of 20 microsatellites DNA was used to investigate fine-scale population structuring of swordfish from six main fishing areas of the Mediterranean Sea. Results This study provides evidence to reject the hypothesis of a single swordfish population within the Mediterranean Sea. DAPC analysis revealed the presence of three genetic clusters and a high level of admixture within the Mediterranean Sea. Genetic structure was supported by significant FST values while mixing was endorsed by the heterozygosity deficit observed in sampling localities indicative of a possible Wahlund effect, by sampling admixture individuals. Overall, our tests reject the hypothesis of a single swordfish population within the Mediterranean Sea. Homing towards the Mediterranean breeding areas may have generated a weak degree of genetic differentiation between populations even at the intra-basin scale

Haplotype characterization of a stranded common minke whale calf (Balaenoptera acutorostrata lacépède, 1804): Is the mediterranean sea a potential calving or nursery ground for the species?

The stranding of a suckling calf of Common Minke Whale (Balaenoptera acutorostrata) on the coast near Salerno (Campania, Southern Italy) is reported. The molecular analysis of a partial sequence of the mitochondrial DNA control region shows that the animal bore a haplotype identical to haplotype Ba169 considered as typical of individuals from North Atlantic population. Historical data and our results suggest the possibility that the Mediterranean Sea might be a potential calving or nursery ground for this species

Semantic Web Applications and Tools for the Life Sciences:SWAT4LS 2010

As Semantic Web technologies mature and new releases of key elements, such as SPARQL 1.1 and OWL 2.0, become available, the Life Sciences continue to push the boundaries of these technologies with ever more sophisticated tools and applications. Unsurprisingly, therefore, interest in the SWAT4LS (Semantic Web Applications and Tools for the Life Sciences) activities have remained high, as was evident during the third international SWAT4LS workshop held in Berlin in December 2010. Contributors to this workshop were invited to submit extended versions of their papers, the best of which are now made available in the special supplement of BMC Bioinformatics. The papers reflect the wide range of work in this area, covering the storage and querying of Life Sciences data in RDF triple stores, tools for the development of biomedical ontologies and the semantics-based integration of Life Sciences as well as clinicial data