Towards a Java Subtyping Operad

The subtyping relation in Java exhibits self-similarity. The self-similarity in Java subtyping is interesting and intricate due to the existence of wildcard types and, accordingly, the existence of three subtyping rules for generic types: covariant subtyping, contravariant subtyping and invariant subtyping. Supporting bounded type variables also adds to the complexity of the subtyping relation in Java and in other generic nominally-typed OO languages such as C# and Scala. In this paper we explore defining an operad to model the construction of the subtyping relation in Java and in similar generic nominally-typed OO programming languages. Operads, from category theory, are frequently used to model self-similar phenomena. The Java subtyping operad, we hope, will shed more light on understanding the type systems of generic nominally-typed OO languages.Comment: 13 page

Semantic subtyping for objects and classes

In this paper we propose an integration of structural subtyping with boolean connectives and semantic subtyping to define a Java-like programming language that exploits the benefits of both techniques. Semantic subtyping is an approach for defining subtyping relation based on set-theoretic models, rather than syntactic rules. On the one hand, this approach involves some non trivial mathematical machinery in the background. On the other hand, final users of the language need not know this machinery and the resulting subtyping relation is very powerful and intuitive. While semantic subtyping is naturally linked to the structural one, we show how our framework can also accommodate the nominal subtyping. Several examples show the expressivity and the practical advantages of our proposal

On the preciseness of subtyping in session types

Subtyping in concurrency has been extensively studied since early 1990s as one of the most interesting issues in type theory. The correctness of subtyping relations has been usually provided as the soundness for type safety. The converse direction, the completeness, has been largely ignored in spite of its usefulness to define the greatest subtyping relation ensuring type safety. This paper formalises preciseness (i.e. both soundness and completeness) of subtyping for mobile processes and studies it for the synchronous and the asynchronous session calculi. We first prove that the well-known session subtyping, the branching-selection subtyping, is sound and complete for the synchronous calculus. Next we show that in the asynchronous calculus, this subtyping is incomplete for type-safety: that is, there exist session types T and S such that T can safely be considered as a subtype of S, but T ≤ S is not derivable by the subtyping. We then propose an asynchronous sub-typing system which is sound and complete for the asynchronous calculus. The method gives a general guidance to design rigorous channel-based subtypings respecting desired safety properties

An evaluation of DNA-damage response and cell-cycle pathways for breast cancer classification

Accurate subtyping or classification of breast cancer is important for ensuring proper treatment of patients and also for understanding the molecular mechanisms driving this disease. While there have been several gene signatures proposed in the literature to classify breast tumours, these signatures show very low overlaps, different classification performance, and not much relevance to the underlying biology of these tumours. Here we evaluate DNA-damage response (DDR) and cell cycle pathways, which are critical pathways implicated in a considerable proportion of breast tumours, for their usefulness and ability in breast tumour subtyping. We think that subtyping breast tumours based on these two pathways could lead to vital insights into molecular mechanisms driving these tumours. Here, we performed a systematic evaluation of DDR and cell-cycle pathways for subtyping of breast tumours into the five known intrinsic subtypes. Homologous Recombination (HR) pathway showed the best performance in subtyping breast tumours, indicating that HR genes are strongly involved in all breast tumours. Comparisons of pathway based signatures and two standard gene signatures supported the use of known pathways for breast tumour subtyping. Further, the evaluation of these standard gene signatures showed that breast tumour subtyping, prognosis and survival estimation are all closely related. Finally, we constructed an all-inclusive super-signature by combining (union of) all genes and performing a stringent feature selection, and found it to be reasonably accurate and robust in classification as well as prognostic value. Adopting DDR and cell cycle pathways for breast tumour subtyping achieved robust and accurate breast tumour subtyping, and constructing a super-signature which contains feature selected mix of genes from these molecular pathways as well as clinical aspects is valuable in clinical practice.Comment: 28 pages, 7 figures, 6 table

Detailed evaluation of data analysis tools for subtyping of bacterial isolates based on whole genome sequencing : Neisseria meningitidis as a proof of concept

Whole genome sequencing is increasingly recognized as the most informative approach for characterization of bacterial isolates. Success of the routine use of this technology in public health laboratories depends on the availability of well-characterized and verified data analysis methods. However, multiple subtyping workflows are now often being used for a single organism, and differences between them are not always well described. Moreover, methodologies for comparison of subtyping workflows, and assessment of their performance are only beginning to emerge. Current work focuses on the detailed comparison of WGS-based subtyping workflows and evaluation of their suitability for the organism and the research context in question. We evaluated the performance of pipelines used for subtyping of Neisseria meningitidis, including the currently widely applied cgMLST approach and different SNP-based methods. In addition, the impact of the use of different tools for detection and filtering of recombinant regions and of different reference genomes were tested. Our benchmarking analysis included both assessment of technical performance of the pipelines and functional comparison of the generated genetic distance matrices and phylogenetic trees. It was carried out using replicate sequencing datasets of high- and low-coverage, consisting mainly of isolates belonging to the clonal complex 269. We demonstrated that cgMLST and some of the SNP-based subtyping workflows showed very good performance characteristics and highly similar genetic distance matrices and phylogenetic trees with isolates belonging to the same clonal complex. However, only two of the tested workflows demonstrated reproducible results for a group of more closely related isolates. Additionally, results of the SNP-based subtyping workflows were to some level dependent on the reference genome used. Interestingly, the use of recombination-filtering software generally reduced the similarity between the gene-by-gene and SNP-based methodologies for subtyping of N. meningitidis. Our study, where N. meningitidis was taken as an example, clearly highlights the need for more benchmarking comparative studies to eventually contribute to a justified use of a specific WGS data analysis workflow within an international public health laboratory context