Prediction of functional microexons by transfer learning

Background Microexons are a particular kind of exon of less than 30 nucleotides in length. More than 60% of annotated human microexons were found to have high levels of sequence conservation, suggesting their potential functions. There is thus a need to develop a method for predicting functional microexons. Results Given the lack of a publicly available functional label for microexons, we employed a transfer learning skill called Transfer Component Analysis (TCA) to transfer the knowledge obtained from feature mapping for the prediction of functional microexons. To provide reference knowledge, microindels were chosen because of their similarities to microexons. Then, Support Vector Machine (SVM) was used to train a classification model in the newly built feature space for the functional microindels. With the trained model, functional microexons were predicted. We also built a tool based on this model to predict other functional microexons. We then used this tool to predict a total of 19 functional microexons reported in the literature. This approach successfully predicted 16 out of 19 samples, giving accuracy greater than 80%. Conclusions In this study, we proposed a method for predicting functional microexons and applied it, with the predictive results being largely consistent with records in the literature.

Temporal variability in quantitative human gut microbiome profiles and implications for clinical research

While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between- and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing. Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics. We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100-fold shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show significant effects. We find that the dysbiotic Bact2 enterotype shows increased between- and within-subject compositional variability. Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.

Evaluation of Age and Sex-Related Metabolic Changes in Healthy Subjects: An Italian Brain 18F-FDG PET Study

Background: 18F-fluorodeoxyglucose (18F-FDG) positron-emission-tomography (PET) allows detection of cerebral metabolic alterations in neurological diseases vs. normal aging. We assess age- and sex-related brain metabolic changes in healthy subjects, exploring impact of activity normalization methods. Methods: brain scans of Italian Association of Nuclear Medicine normative database (151 subjects, 67 Males, 84 Females, aged 20–84) were selected. Global mean, white matter, and pons activity were explored as normalization reference. We performed voxel-based and ROI analyses using SPM12 and IBM-SPSS software. Results: SPM proved a negative correlation between age and brain glucose metabolism involving frontal lobes, anterior-cingulate and insular cortices bilaterally. Narrower clusters were detected in lateral parietal lobes, precuneus, temporal pole and medial areas bilaterally. Normalizing on pons activity, we found a more significant negative correlation and no positive one. ROIs analysis confirmed SPM results. Moreover, a significant age × sex interaction effect was revealed, with worse metabolic reduction in posterior-cingulate cortices in females than males, especially in post-menopausal age. Conclusions: this study demonstrated an age-related metabolic reduction in frontal lobes and in some parieto-temporal areas more evident in females. Results suggested pons as the most appropriate normalization reference. Knowledge of age- and sex-related cerebral metabolic changes is critical to correctly interpreting brain 18F-FDG PET imaging.

MIMOSA2: A metabolic network-based tool for inferring mechanism-supported relationships in microbiome-metabolome data

Motivation: Recent technological developments have facilitated an expansion of microbiome-metabolome studies, in which a set of microbiome samples are assayed using both genomic and metabolomic technologies to characterize the composition of microbial taxa and the concentrations of various metabolites. A common goal of many of these studies is to identify microbial features (species or genes) that contribute to differences in metabolite levels across samples. Previous work indicated that integrating these datasets with reference knowledge on microbial metabolic capacities may enable more precise and confident inference of such microbe-metabolite links. Results: We present MIMOSA2, an R package and web application for model-based integrative analysis of microbiome-metabolome datasets. MIMOSA2 uses reference databases to construct a community metabolic model based on microbiome data and uses this model to predict differences in metabolite levels across samples. These predictions are compared with metabolomics data to identify putative microbiome-governed metabolites and specific taxonomic contributors to metabolite variation. MIMOSA2 supports various input data types and can be customized to incorporate user-defined metabolic pathways. We demonstrate MIMOSA2's ability to identify ground truth microbial mechanisms in simulation datasets, and compare its results with experimentally inferred mechanisms in a dataset describing honeybee gut microbiota. Overall, MIMOSA2 combines reference databases, a validated statistical framework, and a user-friendly interface to facilitate modeling and evaluating relationships between members of the microbiota and their metabolic products. Availability and Implementation: MIMOSA2 is implemented in R under the GNU General Public License v3.0 and is freely available as a web server and R package from www.borensteinlab.com/software_MIMOSA2.html.

Antimicrobial Resistance of Non-Typhoid Salmonella in Meat and Meat Products

Salmonella enterica serovars are associated with numerous annual deaths worldwide and are responsible for a large number of foodborne diseases. Within this frame of reference, knowledge of antimicrobial susceptibility represents the fundamental approach of most Salmonella treatments. Therefore, scientific publications of antimicrobial susceptibilities and resistance must be precise, with interpretations adjusted to a particular standard. Hence, the three objectives in this study were: (i) to describe the frequency of antimicrobial-resistant isolates of Non-Typhoidal Salmonella (NTS) isolated from beef, pork, chicken meat, and other meat products; (ii) to describe the distribution of serovars and their multi-resistance to antibiotics for clinical use (veterinary and human) between 1996 and 2019; and (iii) to propose additional considerations that could improve the use and usefulness of the published results. Our results determined that the predominant isolates came from poultry. Enteritidis and Typhimurium were the most reported serovars by MIC (with both having the highest resistance to TET) while the lowest resistance was to CIP and CRO for Enteritidis and Typhimurium, respectively. The multi-resistance pattern AMP AMC CEP GEN KAN STR TET was the most frequently observed pattern by MIC in Montevideo and Seftenberg, while, for disc diffusion, the pattern AMP STR TET was the most frequent in the Bredeney serotype. In conclusion, researchers should carry out homogeneous sampling procedures, identify the types of the samples, use standard identification methods, and employ appropriate standards for antimicrobial susceptibility interpretation. Additionally, there is also a need for all WHO members to comply with the WHA 73.5 resolution. Our final recommendation is for all producers to reduce antibiotic prophylactic use.

Security basic model for applied tasks of the distributed information system

The tasks of modelling and the components of the basic model of applied task protection of a distributed information system have been considered. The measurement and relationship of security parameters, protection, new and reference attacks, anomalies, and threat environments have been proposed. The conditions of threats, attacks and, consequently, inconsistencies in the results of applied tasks are proved. At the beginning of the article the concept of a distributed information system, system of applied tasks, modern trends of zero-trust architecture in building information security systems are discussed. Further, it gives an overview of existing methods of detection and counteraction to attacks based on reference knowledge bases. To improve the level of security it is proposed to analyze the causes of attacks, namely hazards and threats to the system. Attacks, hazards and threats are considered as structured processes that affect the internal and external environment of the system of the applied tasks with a further impact on the output of these tasks. The concepts of security level and security level of a distributed information system are introduced, as well as the concepts of applied task, environment, and user contradictions. As the logical metrics of discrepancy detection the apparatus of semantic analysis is proposed, which (based on the reference knowledge base, the apparatus of text transformations) should be applied at the stage of loading of applied task and describe the input and output data, requirements to the environment of the task solution. The result of the research is the proposed method for identifying additional data about hazards, threats, attacks, countermeasures to attacks, applied task-solving. This data is generated from the reference and augmented textual descriptions derived from the proposed contradictions. By building additional reference images of threats, attacks, countermeasures, it becomes possible to prevent the activation of new attacks on the distributed information system.

Teaching and Learning Floating and Sinking: Didactic Transformation in a Density-Based Approach

This essay synthesizes more than a decade of research, most of which has been published, on the teaching and learning of floating and sinking (FS) phenomena. The research is comprised of the iterative design, development, implementation and evaluation of a Teaching-Learning sequence (TLS) for the teaching and learning of density within FS phenomena. It was initiated within the frame of the European Community supported “Materials Science” project. Due to the many, different aspects of the project, each publication has focused on a particular part of the study (e.g., effectiveness and the iteration process). The didactic transformation for the teaching of FS phenomena is presented and discussed here. In doing so, it is essential to mention: (a) the students’ ideas as the main cause of the scientific knowledge transformation, (b) the scientific/reference knowledge, and (c) the knowledge to be taught and its limitations. Thus, we intend to describe and justify the didactic transformation process and briefly synthesize the published (from previous papers) and unpublished results to show its effectiveness.

The Use of Storytelling to Promote Literacy Skills in Biology Education

This chapter provides biology teachers with a cell division-based teaching sequence to develop the literacy skills of 10th grade students using the storytelling potential. The objectives are 1) to analyze the design process of this sequence and 2) to examine how it is implemented in two classrooms in terms of a communicative approach. The sequence design is informed by the didactical transposition approach. The authors analyze the transformation of reference knowledge, firstly, into a teaching sequence of four activities organized around authentic issues, such as cancer treatment or reproductive problems, and then, into taught knowledge. The results show that the use of storytelling in design could enhance students' scientific literacy, scientific discourse, and problem-solving competence, as it allows for their greater participation (80-90% of utterances). Interactive approaches (8/10 episodes) predominate in experts-learners discussions, improving students' view of science as a process and not as a closed set of notions.

THE MEDICAL INFORMATION SYSTEM CONCEPT FOR ACUTE LYMPHOBLASTIC LEUKEMIA DIAGNOSING

Continuous improvement of software and hardware platforms makes it possible to significant-ly expand the development capabilities of modern medical information systems (MIS) to reach a qualitatively new level associated with the transition to the creation of universal cross-platform web-applications. The article discusses the concept of the implementation of MIS for the diagnosis of acute leu-kemia (AL) and minimal residual disease (MRD) through the complex integration of systems based on laser flow cytometry (an integrated method for diagnosing hemoblastosis), intelli-gent computer microscopy based on expert neural network analyzer for recognition of blast cell images based on formed reference knowledge base. When making a diagnosis, this MIS will allow doctors to work with information about patients directly through the system inter-face by comparing data about new patients with images of an expert database and then sub-sequent generate the diagnostic conclusion based on the results of the studies performed. Data security in the system is ensured by the web server administration regulations and the division of access rights for various categories of users. MIS provides an opportunity for a comprehensive diagnostic study of patients making decisions about the tactics of treatment.

Exploring Integrative Analysis Using the BioMedical Evidence Graph

PURPOSE The analysis of cancer biology data involves extremely heterogeneous data sets, including information from RNA sequencing, genome-wide copy number, DNA methylation data reporting on epigenetic regulation, somatic mutations from whole-exome or whole-genome analyses, pathology estimates from imaging sections or subtyping, drug response or other treatment outcomes, and various other clinical and phenotypic measurements. Bringing these different resources into a common framework, with a data model that allows for complex relationships as well as dense vectors of features, will unlock integrated data set analysis. METHODS We introduce the BioMedical Evidence Graph (BMEG), a graph database and query engine for discovery and analysis of cancer biology. The BMEG is unique from other biologic data graphs in that sample-level molecular and clinical information is connected to reference knowledge bases. It combines gene expression and mutation data with drug-response experiments, pathway information databases, and literature-derived associations. RESULTS The construction of the BMEG has resulted in a graph containing > 41 million vertices and 57 million edges. The BMEG system provides a graph query–based application programming interface to enable analysis, with client code available for Python, Javascript, and R, and a server online at bmeg.io. Using this system, we have demonstrated several forms of cross–data set analysis to show the utility of the system. CONCLUSION The BMEG is an evolving resource dedicated to enabling integrative analysis. We have demonstrated queries on the system that illustrate mutation significance analysis, drug-response machine learning, patient-level knowledge-base queries, and pathway level analysis. We have compared the resulting graph to other available integrated graph systems and demonstrated the former is unique in the scale of the graph and the type of data it makes available.