RESUMO
This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Resistencia a Medicamentos Antineoplásicos , Expressão Gênica , Genes Supressores de Tumor , Humanos , Mesilato de Imatinib/uso terapêutico , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Monoéster Fosfórico Hidrolases/genética , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição/genéticaRESUMO
The COVID-19 pandemic has highlighted the need to take advantage of specific and effective patient telemonitoring platforms, with specific reference to the constant monitoring of vital parameters of patients most at risk. Among the various applications developed in Italy, certainly there is reCOVeryaID, a web application aimed at remotely monitoring patients potentially, currently or no longer infected with COVID-19. Therefore, in this paper we present a system model, consisting of a multi-platform intelligent telemonitoring application, that enables remote monitoring and provision of integrated home care to both patients symptomatic, asymptomatic and pre-symptomatic with severe acute respiratory infectious disease or syndrome caused by viruses belonging to the Coronavirus family, as well as simply to people with respiratory problems and/or related diseases (chronic obstructive pulmonary disease or asthma). In fact, in this paper we focus on exposing the technologies and various functionalities offered by the system, which constitute the practical implementation of the theoretical framework described in detail in another paper. Specifically, the reCOVeryaID telemonitoring application is a stand-alone, knowledge base-supported application that can promptly react and inform physicians if dangerous trends in a patient's short- and long-term vital signs are detected, thus enabling them to be monitored continuously, both in the hospital and at home. The paper also reports an evaluation of user satisfaction, carried out by actual patients and medical doctors.
RESUMO
The COVID-19 emergency underscored the importance of resolving crucial issues of territorial health monitoring, such as overloaded phone lines, doctors exposed to infection, chronically ill patients unable to access hospitals, etc. In fact, it often happened that people would call doctors/hospitals just out of anxiety, not realizing that they were clogging up communications, thus causing problems for those who needed them most; such people, often elderly, have often felt lonely and abandoned by the health care system because of poor telemedicine. In addition, doctors were unable to follow up on the most serious cases or make sure that others did not worsen. Thus, uring the first pandemic wave we had the idea to design a system that could help people alleviate their fears and be constantly monitored by doctors both in hospitals and at home; consequently, we developed reCOVeryaID, a telemonitoring application for coronavirus patients. It is an autonomous application supported by a knowledge base that can react promptly and inform medical doctors if dangerous trends in the patient's short- and long-term vital signs are detected. In this paper, we also validate the knowledge-base rules in real-world settings by testing them on data from real patients infected with COVID-19.
RESUMO
In this tutorial, we learn how to set up and exploit the virtual knowledge graph (VKG) approach to access data stored in relational legacy systems and to enrich such data with domain knowledge coming from different heterogeneous (biomedical) resources. The VKG approach is based on an ontology that describes a domain of interest in terms of a vocabulary familiar to the user and exposes a high-level conceptual view of the data. Users can access the data by exploiting the conceptual view, and in this way they do not need to be aware of low-level storage details. They can easily integrate ontologies coming from different sources and can obtain richer answers thanks to the interaction between data and domain knowledge.