Ontology mapping: a logic-based approach with applications in selected domains

In advent of the Semantic Web and recent standardization efforts, Ontology has quickly become a popular and core semantic technology. Ontology is seen as a solution provider to knowledge based systems. It facilitates tasks such as knowledge sharing, reuse and intelligent processing by computer agents. A key problem addressed by Ontology is the semantic interoperability problem. Interoperability in general is a common problem in different domain applications and semantic interoperability is the hardest and an ongoing research problem. It is required for systems to exchange knowledge and having the meaning of the knowledge accurately and automatically interpreted by the receiving systems. The innovation is to allow knowledge to be consumed and used accurately in a way that is not foreseen by the original creator. While Ontology promotes semantic interoperability across systems by unifying their knowledge bases through consensual understanding, common engineering and processing practices, it does not solve the semantic interoperability problem at the global level. As individuals are increasingly empowered with tools, ontologies will eventually be created more easily and rapidly at a near individual scale. Global semantic interoperability between heterogeneous ontologies created by small groups of individuals will then be required. Ontology mapping is a mechanism for providing semantic bridges between ontologies. While ontology mapping promotes semantic interoperability across ontologies, it is seen as the solution provider to the global semantic interoperability problem. However, there is no single ontology mapping solution that caters for all problem scenarios. Different applications would require different mapping techniques. In this thesis, we analyze the relations between ontology, semantic interoperability and ontology mapping, and promote an ontology-based semantic interoperability solution. We propose a novel ontology mapping approach namely, OntoMogic. It is based on first order logic and model theory. OntoMogic supports approximate mapping and produces structures (approximate entity correspondence) that represent alignment results between concepts. OntoMogic has been implemented as a coherent system and is applied in different application scenarios. We present case studies in the network configuration, security intrusion detection and IT governance & compliance management domain. The full process of ontology engineering to mapping has been demonstrated to promote ontology-based semantic interoperability

Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development

Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.published_or_final_versio

Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma

Therapy-induced tumour microenvironment (TME) remodelling poses a major hurdle for cancer cure. As the majority of patients with hepatocellular carcinoma (HCC) exhibits primary or acquired resistance to antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) therapies, we aimed to investigate the mechanisms underlying tumour adaptation to immune-checkpoint targeting.Published versionThis project is supported by the Collaborative Research Fund (C4045-18W to AS-LC), the General Research Fund (14115820 and 14120621 to AS-LC), the Li Ka Shing Foundation (grant number not applicable to YMDL, AS-LC), the Health and Medical Research Fund (07180556 to JZ), the Terry Fox Foundation—Terry Fox Run, Hong Kong (I1008 to SLC, AS-LC), the CUHK Strategic Seed Funding for Collaborative Research Scheme (grant number not applicable to AS-LC) and the Charlie Lee Charitable Foundation (grant number not applicable). We also acknowledge support (funding and study medications) by Merck Sharp and Dohme (MSD-IIS 55253 to SLC) for the clinical trial (NCT03419481)

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field