Comprehensive Analysis of Circular RNAs in Endothelial Cells.

Non-coding RNAs constitute a heterogeneous group of molecules that lack the ability to encode proteins but retain the potential ability to influence cellular processes through a regulatory mechanism. Of these proteins, microRNAs, long non-coding RNAs, and more recently, circular RNAs have been the most extensively described. However, it is not entirely clear how these molecules interact with each other. For circular RNAs, the basics of their biogenesis and properties are also lacking. Therefore, in this study we performed a comprehensive analysis of circular RNAs in relation to endothelial cells. We identified the pool of circular RNAs present in the endothelium and showed their spectrum and expression across the genome. Using different computational strategies, we proposed approaches to search for potentially functional molecules. In addition, using data from an in vitro model that mimics conditions in the endothelium of an aortic aneurysm, we demonstrated altered expression levels of circRNAs mediated by microRNAs.

On the Dependence of Prion and Amyloid Structure on the Folding Environment.

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations-globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.

Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients.

Malignant gliomas are the most frequent primary brain tumors in adults. They are genetically heterogenous and invariably recur due to incomplete surgery and therapy resistance. Circulating tumor DNA (ctDNA) is a component of circulating cell-free DNA (ccfDNA) and represents genetic material that originates from the primary tumor or metastasis. Brain tumors are frequently located in the eloquent brain regions, which makes biopsy difficult or impossible due to severe postoperative complications. The analysis of ccfDNA from a patient's blood presents a plausible and noninvasive alternative. In this study, freshly frozen tumors and corresponding blood samples were collected from 84 brain tumor patients and analyzed by targeted next-generation sequencing (NGS). The cohort included 80 glioma patients, 2 metastatic cancer patients, and 2 primary CNS lymphoma (PCNSL) patients. We compared the pattern of genetic alterations in the tumor DNA (tDNA) with that of ccfDNA. The implemented technical improvements in quality control and library preparation allowed for the detection of ctDNA in 8 out of 84 patients, including 5 out of 80 glioma patients. In 32 out of 84 patients, we found potentially pathogenic genetic alterations in ccfDNA that were not detectable in tDNA. While sequencing ccfDNA from plasma has a low efficacy as a diagnostic tool for glioma patients, we concluded that further improvements in sample processing and library preparation can make liquid biopsy a valuable diagnostic tool for glioma patients.

MiR-191 as a Key Molecule in Aneurysmal Aortic Remodeling.

Abdominal aortic aneurysms (AAA) are a complex disease with an unclear pathomechanism. A positive family history is emphasized as a significant risk factor, and a nonspecific model of inheritance suggests participation of epigenetic regulation in the pathogenesis of this disease. Past studies have implicated microRNAs in the development of AAA; therefore in this project, we measured miR-191 levels in AAA patients and compared them with a control group. We found that miR-191 levels were significantly elevated in aneurysmal patients, although this did not correlate with the available clinical data. We then developed an in vitro model where, using cells with an endothelial phenotype, we determined the effect of miR-191 on the transcriptome using RNA sequencing. Subsequent pathway analysis established that some of the perturbations mediated by miR-191 can be explained by several processes which have long been observed and described in literature as accompanying the development of abdominal aortic aneurysms.

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins.

The natural environment of proteins is the polar aquatic environment and the hydrophobic (amphipathic) environment of the membrane. The fuzzy oil drop model (FOD) used to characterize water-soluble proteins, as well as its modified version FOD-M, enables a mathematical description of the presence and influence of diverse environments on protein structure. The present work characterized the structures of membrane proteins, including those that act as channels, and a water-soluble protein for contrast. The purpose of the analysis was to verify the possibility that an external force field can be used in the simulation of the protein-folding process, taking into account the diverse nature of the environment that guarantees a structure showing biological activity.

PRIMAGE project: predictive in silico multiscale analytics to support childhood cancer personalised evaluation empowered by imaging biomarkers.

PRIMAGE is one of the largest and more ambitious research projects dealing with medical imaging, artificial intelligence and cancer treatment in children. It is a 4-year European Commission-financed project that has 16 European partners in the consortium, including the European Society for Paediatric Oncology, two imaging biobanks, and three prominent European paediatric oncology units. The project is constructed as an observational in silico study involving high-quality anonymised datasets (imaging, clinical, molecular, and genetics) for the training and validation of machine learning and multiscale algorithms. The open cloud-based platform will offer precise clinical assistance for phenotyping (diagnosis), treatment allocation (prediction), and patient endpoints (prognosis), based on the use of imaging biomarkers, tumour growth simulation, advanced visualisation of confidence scores, and machine-learning approaches. The decision support prototype will be constructed and validated on two paediatric cancers: neuroblastoma and diffuse intrinsic pontine glioma. External validation will be performed on data recruited from independent collaborative centres. Final results will be available for the scientific community at the end of the project, and ready for translation to other malignant solid tumours.

Introducing the Brassica Information Portal: Towards integrating genotypic and phenotypic Brassica crop data.

The Brassica Information Portal (BIP) is a centralised repository for brassica phenotypic data. The site hosts trait data associated with brassica research and breeding experiments conducted on brassica crops, that are used as oilseeds, vegetables, livestock forage and fodder and for biofuels. A key feature is the explicit management of meta-data describing the provenance and relationships between experimental plant materials, as well as trial design and trait descriptors. BIP is an open access and open source project, built on the schema of CropStoreDB, and as such can provide trait data management strategies for any crop data. A new user interface and programmatic submission/retrieval system helps to simplify data access for researchers, breeders and other end-users. BIP opens up the opportunity to apply integrative, cross-project analyses to data generated by the Brassica Research Community. Here, we present a short description of the current status of the repository.

DNA microarray integromics analysis platform.

BACKGROUND: The study of interactions between molecules belonging to different biochemical families (such as lipids and nucleic acids) requires specialized data analysis methods. This article describes the DNA Microarray Integromics Analysis Platform, a unique web application that focuses on computational integration and analysis of "multi-omics" data. Our tool supports a range of complex analyses, including - among others - low- and high-level analyses of DNA microarray data, integrated analysis of transcriptomics and lipidomics data and the ability to infer miRNA-mRNA interactions. RESULTS: We demonstrate the characteristics and benefits of the DNA Microarray Integromics Analysis Platform using two different test cases. The first test case involves the analysis of the nutrimouse dataset, which contains measurements of the expression of genes involved in nutritional problems and the concentrations of hepatic fatty acids. The second test case involves the analysis of miRNA-mRNA interactions in polysaccharide-stimulated human dermal fibroblasts infected with porcine endogenous retroviruses. CONCLUSIONS: The DNA Microarray Integromics Analysis Platform is a web-based graphical user interface for "multi-omics" data management and analysis. Its intuitive nature and wide range of available workflows make it an effective tool for molecular biology research. The platform is hosted at https://lifescience.plgrid.pl/.