A knowledge base for the discovery of function, diagnostic potential and drug effects on cellular and extracellular miRNAs

Background: MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular mRNAs. A significant amount of miRNAs has been found in extracellular human body fluids (e.g. plasma and serum) and some circulating miRNAs in the blood have been successfully revealed as biomarkers for diseases including cardiovascular diseases and cancer. Released miRNAs do not necessarily reflect the abundance of miRNAs in the cell of origin. It is claimed that release of miRNAs from cells into blood and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. Moreover, miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function. In particular, the use of drugs should be taken into consideration while analyzing plasma miRNA levels as drug treatment. This may impair their employment as biomarkers. Description: We enriched our manually curated extracellular/circulating microRNAs database, miRandola, by providing (i) a systematic comparison of expression profiles of cellular and extracellular miRNAs, (ii) a miRNA targets enrichment analysis procedure, (iii) information on drugs and their effect on miRNA expression, obtained by applying a natural language processing algorithm to abstracts obtained from PubMed. Conclusions: This allows users to improve the knowledge about the function, diagnostic potential, and the drug effects on cellular and circulating miRNAs

From a Conceptual Model to a Knowledge Graph for Genomic Datasets

Data access at genomic repositories is problematic, as data is described by heterogeneous and hardly comparable metadata. We previously introduced a unified conceptual schema, collected metadata in a single repository and provided classical search methods upon them. We here propose a new paradigm to support semantic search of integrated genomic metadata, based on the Genomic Knowledge Graph, a semantic graph of genomic terms and concepts, which combines the original information provided by each source with curated terminological content from specialized ontologies. Commercial knowledge-assisted search is designed for transparently supporting keyword-based search without explaining inferences; in biology, inference understanding is instead critical. For this reason, we propose a graph-based visual search for data exploration; some expert users can navigate the semantic graph along the conceptual schema, enriched with simple forms of homonyms and term hierarchies, thus understanding the semantic reasoning behind query results

The Cyborg Astrobiologist: Testing a Novelty-Detection Algorithm on Two Mobile Exploration Systems at Rivas Vaciamadrid in Spain and at the Mars Desert Research Station in Utah

(ABRIDGED) In previous work, two platforms have been developed for testing computer-vision algorithms for robotic planetary exploration (McGuire et al. 2004b,2005; Bartolo et al. 2007). The wearable-computer platform has been tested at geological and astrobiological field sites in Spain (Rivas Vaciamadrid and Riba de Santiuste), and the phone-camera has been tested at a geological field site in Malta. In this work, we (i) apply a Hopfield neural-network algorithm for novelty detection based upon color, (ii) integrate a field-capable digital microscope on the wearable computer platform, (iii) test this novelty detection with the digital microscope at Rivas Vaciamadrid, (iv) develop a Bluetooth communication mode for the phone-camera platform, in order to allow access to a mobile processing computer at the field sites, and (v) test the novelty detection on the Bluetooth-enabled phone-camera connected to a netbook computer at the Mars Desert Research Station in Utah. This systems engineering and field testing have together allowed us to develop a real-time computer-vision system that is capable, for example, of identifying lichens as novel within a series of images acquired in semi-arid desert environments. We acquired sequences of images of geologic outcrops in Utah and Spain consisting of various rock types and colors to test this algorithm. The algorithm robustly recognized previously-observed units by their color, while requiring only a single image or a few images to learn colors as familiar, demonstrating its fast learning capability.Comment: 28 pages, 12 figures, accepted for publication in the International Journal of Astrobiolog

i-DATAQUEST : a Proposal for a Manufacturing Data Query System Based on a Graph

During the manufacturing product life cycle, an increasing volume of data is generated and stored in distributed resources. These data are heterogeneous, explicitly and implicitly linked and they could be structured and unstructured. The rapid, exhaustive and relevant acquisition of information from this data is a major manufacturing industry issue. The key challenges, in this context, are to transform heterogeneous data into a common searchable data model, to allow semantic search, to detect implicit links between data and to rank results by relevance. To address this issue, the authors propose a query system based on a graph database. This graph is defined based on all the transformed manufacturing data. Besides, the graph is enriched by explicitly and implicitly data links. Finally, the enriched graph is queried thanks to an extended queries system defined by a knowledge graph. The authors depict a proof of concept to validate the proposal. After a partial implementation of this proof of concept, the authors obtain an acceptable result and a needed effort to improve the system response time. Finally, the authors open the topic on the subjects of right management, user profile/customization and data update.Chaire ENSAM-Capgemini sur le PLM du futu

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (T1DGC)

Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide

Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19

Background and objectives: Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS-CoV-2. Methods: This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry. Results: BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS-CoV-2. Conclusions: The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19