Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. CONCLUSIONS: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. Circ Genom Precis Med 2018 Feb; 11(2):e001813

IDENTIFICATION OF A MOLECULAR SIGNATURE PREDICTIVE OF REFRACTORINESS IN ACUTE MYELOID LEUKEMIA

Acute Myeloid Leukemia (AML) blast cells are immature committed myeloid cells unable to spontaneously undergo terminal maturation, characterized by heterogeneous sensitivity to natural differentiation inducers. No data are available so far by which infer the AML’s response to differentiating therapy. Thus, we have initially profiled by GeneChip arrays the gene expression of several AML cell lines: they derived by the original blast cell populations and are still characterized by the same immunophenotype, retain a different sensitivity or resistance to ATRA and VD and never undergo spontaneously terminal maturation. Here we show that differences exist by which predict the cell line differentiation fate. Next we constructed a signature able to predict resistance or sensitivity to the differentiation induction and tested it, using a TaqMan platform, for its capability to predict the in-vitro response of 28 VD or ATRA treated AML blast cell populations. Finally, by a meta-analysis of public available microarray data we demonstrated that our signature, that was formerly designed to identify differentiation therapy resistant populations, turned out to be a good classifier for clusters of patients with citogenetically and molecularly defined lesions that are known to have poor prognostic significance

TRANSFORMATION AND RESOURCES IN THE "NEW" GEO-ECONOMY

The essay addresses the big changes that took place in the geo-economy of manufacturing as a result of the amazing growth of the Asian economies, especially China’s, over the last three decades. The indicators used in order to assess the extent of the change are the consumption data of 11 industrial raw materials (the 6 main non-ferrous metals: copper, aluminium, lead, zinc, tin and nickel; plus crude steel, rubber, plastic materials, wood-based panels, paper and paperboard) in the G-20 countries. The figures were compared to the data of the evolution of the manufacturing output worldwide to measure the degree of shifting of its center of gravity from North America and Europe towards Asia. Both statistical methods lead to the conclusion that the distribution of the manufacturing output in the world has been changing remarkably in the last 10 to 15 years, moving eastward: while in the year 2000 the United States still held 24.8% of the world output in current dollars, in 2007, though still at the top, its share dropped to 18.2% and in 2010 China ranked first with a 21.7% share. After Japan and Germany, that retain the third and fourth positions respectively among manufacturing producers, India and South Korea rose sharply to the fifth and sixth positions. Italy ranked seventh. At the same time a progressive rise was observed in basic product consumption in industrial processing. The United States, the first world consumer in 9 basic products out of 11 in 1980, lost its record in the use of industrial materials in 2010, replaced by China. As regards Italy, in Europe our country was second after Germany in the use of industrial materials throughout the period from 1980 to 2010