An Automated System for the Assessment and Ranking of Domain Ontologies

As the number of intelligent software applications and the number of semantic websites continue to expand, ontologies are needed to formalize shared terms. Often it is necessary to either find a previously used ontology for a particular purpose, or to develop a new one to meet a specific need. Because of the challenge involved in creating a new ontology from scratch, the latter option is often preferable. The ability of a user to select an appropriate, high-quality domain ontology from a set of available options would be most useful in knowledge engineering and in developing intelligent applications. Being able to assess an ontology\u27s quality and suitability is also important when an ontology is developed from the beginning. These capabilities, however, require good quality assessment mechanisms as well as automated support when there are a large number of ontologies from which to make a selection. This thesis provides an in-depth analysis of the current research in domain ontology evaluation, including the development of a taxonomy to categorize the numerous directions the research has taken. Based on the lessons learned from the literature review, an approach to the automatic assessment of domain ontologies is selected and a suite of ontology quality assessment metrics grounded in semiotic theory is presented. The metrics are implemented in a Domain Ontology Rating System (DoORS), which is made available as an open source web application. An additional framework is developed that would incorporate this rating system as part of a larger system to find ontology libraries on the web, retrieve ontologies from them, and assess them to select the best ontology for a particular task. An empirical evaluation in four phases shows the usefulness of the work, including a more stringent evaluation of the metrics that assess how well an ontology fits its domain and how well an ontology is regarded within its community of users

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Genome organization of <i>Arthrobacter</i> phage Amigo, Cluster AQ.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180517#pone.0180517.g005" target="_blank">Fig 5</a> for details.</p

Genome organization of <i>Arthrobacter</i> phage Maggie, Cluster AN.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180517#pone.0180517.g005" target="_blank">Fig 5</a> for details.</p

Nucleotide sequence comparison of <i>Arthrobacter</i> phages.

<p>Dot Plot of <i>Arthrobacter</i> phage genomes displayed using Gepard [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180517#pone.0180517.ref035" target="_blank">35</a>]. Individual genome sequences were concatenated into a single file arranged such that related genomes were adjacent to each other. The assignment of clusters is shown along both the left and bottom.</p

Splitstree representation of <i>Arthrobacter</i> phages and average nucleotide comparisons of Cluster AO <i>Arthrobacter</i> phages.

<p>All <i>Arthrobacter</i> phage predicted proteins were assorted into 1052 phams according to shared amino acid sequence similarities. Each genome was then assigned a value reflecting the presence or absence of a pham member, and the genomes were compared and displayed using Splitstree [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180517#pone.0180517.ref036" target="_blank">36</a>]. Cluster and subcluster assignments derived from the dot plot and ANI analyses are annotated. The scale bar indicates 0.001 substitutions/site.</p

Genome organization of <i>Arthrobacter</i> phage Laroye, Cluster AL.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180517#pone.0180517.g005" target="_blank">Fig 5</a> for details.</p