OmicsON : integration of omics data with molecular networks and statistical procedures

A huge amount of atomized biological data collected in various databases and the need for a description of their relation by theoretical methods causes the development of data integration methods. The omics data analysis by integration of biological knowledge with mathematical procedures implemented in the OmicsON R library is presented in the paper. OmicsON is a tool for the integration of two sets of data: transcriptomics and metabolomics. In the workflow of the library, the functional grouping and statistical analysis are applied. Subgroups among the transcriptomic and metabolomics sets are created based on the biological knowledge stored in Reactome and String databases. It gives the possibility to analyze such sets of data by multivariate statistical procedures like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). The integration of metabolomic and transcriptomic data based on the methodology contained in OmicsON helps to easily obtain information on the connection of data from two different sets. This information can significantly help in assessing the relationship between gene expression and metabolite concentrations, which in turn facilitates the biological interpretation of the analyzed process

Identification of differentiating metabolic pathways between infant gut microbiome populations reveals depletion of function-level adaptation to human milk in the finnish population

ABSTRACT A variety of autoimmune and allergy events are becoming increasingly common, especially in Western countries. Some pieces of research link such conditions with the composition of microbiota during infancy. In this period, the predominant form of nutrition for gut microbiota is oligosaccharides from human milk (HMO). A number of gut-colonizing strains, such as Bifidobacterium and Bacteroides, are able to utilize HMO, but only some Bifidobacterium strains have evolved to digest the specific composition of human oligosaccharides. Differences in the proportions of the two genera that are able to utilize HMO have already been associated with the frequency of allergies and autoimmune diseases in the Finnish and the Russian populations. Our results show that differences in terms of the taxonomic annotation do not explain the reason for the differences in the Bifidobacterium/Bacteroides ratio between the Finnish and the Russian populations. In this paper, we present the results of function-level analysis. Unlike the typical workflow for gene abundance analysis, BiomeScout technology explains the differences in the Bifidobacterium/Bacteroides ratio. Our research shows the differences in the abundances of the two enzymes that are crucial for the utilization of short type 1 oligosaccharides. IMPORTANCE Knowing the limitations of taxonomy-based research, there is an emerging need for the development of higher-resolution techniques. The significance of this research is demonstrated by the novel method used for the analysis of function-level metagenomes. BiomeScout—the presented technology—utilizes proprietary algorithms for the detection of differences between functionalities present in metagenomic samples

Large extracellular vesicles do not mitigate the harmful effect of hyperglycemia on endothelial cell mobility

Extracellular vesicles, especially the larger fraction (LEVs – large extracellular vesicles), are believed to be an important means of intercellular communication. Earlier studies on LEVs have shown their healing properties, especially in the vascular cells of diabetic patients. Uptake of LEVs by endothelial cells and internalization of their cargo have also been demonstrated. Endothelial cells change their properties under hyperglycemic conditions (HGC), which reduces their activity and is the cause of endothelial dysfunction. The aim of our study was to investigate how human umbilical vein endothelial cells (HUVECs) change their biological properties: shape, mobility, cell surface stiffness, as well as describe the activation of metabolic pathways after exposure to the harmful effects of HGC and the administration of LEVs released by endothelial cells. We obtained LEVs from HUVEC cultures in HGC and normoglycemia (NGC) using the filtration and ultracentrifugation methods. We assessed the size of LEVs and the presence of biomarkers such as phosphatidylserine, CD63, beta-actin and HSP70. We analyzed the LEVs uptake efficiency by HUVECs, HUVEC shape, actin cytoskeleton remodeling, surface stiffness and finally gene expression by mRNA analysis. Under HGC conditions, HUVECs were larger and had a stiffened surface and a strengthened actin cortex compared to cells under NGC condition. HGC also altered the activation of metabolic pathways, especially those related to intracellular transport, metabolism, and organization of cellular components. The most interesting observation in our study is that LEVs did not restore cell motility disturbed by HGC. Although, LEVs were not able to reverse this deleterious effect of HGC, they activated transcription of genes involved in protein synthesis and vesicle trafficking in HUVECs

Microvesicles microRNA transcriptomes dataset for human melanoma cell cultures

Udowodniono, że microRNA pochodzące z ektosomów odgrywa ważną rolę w genezie oraz progresji czerniaka skóry. Celem niniejszej pracy było wygenerowanie zbioru transkryptomicznych danych microRNA dla linii czerniaka skóry o zróżnicowanym stopniu złośliwości. Wykorzystano cztery modele linii komórkowych: WM115 pierwotna linia w fazie wzrostu pionowego; WM266-4 przerzut z węzłów chłonnych w fazie wzrostu pionowego; WM793 pierwotna linia w fazie wzrostu pionowego oraz WM1205Lu przerzut wyizolowany z płuca myszy w fazie wzrostu pionowego. Banki komórkowe WM115, WM266-4, WM793, WM1205Lu pochodzą z the European Searchable Tumour Cell Line and Data Bank (ESTDAB)- A Collection of Immunologically Characterised Melanoma Cell Lines and Databank (Tübingen, Germany). Dane zostały wygenerowanie z użyciemplatformy sekwencjonowania nowej generacji Illumina.Microvesicles microRNA have been shown to play an important role in human melanoma development and progression. The aim of this study was to generate transcriptome microRNA dataset for human skin melanoma with different metastatic potential. We used four melanoma cell lines models: WM115 primary vertical growth phase; WM266-4 lymph node metastasis vertical growth phase; WM793 primary vertical growth phase and WM1205Lu metastatic vertical growth phase from nude mice lung metastases. Cell banks of WM115, WM266-4, WM793, WM1205Lu originated from the European Searchable Tumour Cell Line and Data Bank (ESTDAB)- A Collection of Immunologically Characterised Melanoma Cell Lines and Databank (Tübingen, Germany). Data was generated using next-generation sequencing Illumina platform

Surface graphitization process of SiC(0001).

Grafen syntezowany był w ultrawysokiej próżni na powierzchni SiC o politypie 4H i orientacji (0001), poprzez wygrzewanie SiC do temperatur około 1700K. Uzyskane tą techniką próbki charakteryzowano przy pomocy kilku technik badawczych. Spektroskopia Ramana została wykorzystana do określenia optymalnej temperatury grafityzacji. Dyfraktometria niskoenergetycznych elektronów (LEED) oraz kątowo- rozdzielcza spektroskopia fotoelektronów (ARPES), pozwoliły zbadać odpowiednio: periodyczność sieci krystalicznej powierzchni oraz jej strukturę elektronową.Graphene films are synthetized in ultrahigh vacuum on 4H-SiC (0001) surface, at the temperature around 1700 K, by desorption of silicon. Several techniques are applied for diagnostics of the obtained films. Raman spectroscopy is used in order to find the temperature of the graphitization onset. Low energy electron difraction (LEED) and angle resolved photoemission spectroscopy (ARPES) are used to study the surface atomic and electronic structure

Multicomponent layers of polymer with the conductive polymer - surface properties and protein adsorption

Celem pracy było opracowanie strategii tworzenia nanowarstw polimerowych o zadanej strukturze (kolumnowej lub warstwowej) z mieszanin zawierających polimer przewodzący, do zastosowania do przestrzennie kontrolowanej adsorpcji białek. W tym celu wykorzystano mieszaniny polimeru przewodzącego (P3BT lub P3HT) z polimerem izolującym (PMMA), z których przygotowano nanowarstwy polimerowe na podłożach o różnej energii powierzchniowej (krzem, krzem funkcjonalizowany silanami), modyfikując w ten sposób proces separacji faz. Topografie uzyskanych nanowarstw analizowano za pomocą mikroskopii sił atomowych, natomiast jej morfologie za pomocą mikroskopii fluorescencyjnej oraz spektroskopii masowej jonów wtórnych. Dodatkowo sprawdzono, że dla nanowarstw o układzie kolumnowym możliwa jest selektywna adsorpcja białka (surowiczej albuminy wołowej (BSA)) do jednego z polimerów.The aim of this study was to develop a strategy of creating polymer nanolayers of given structure (columnar or layered) from mixtures containing a conductive polymer, to be used for spatially controlled adsorption of proteins. For this purpose the mixture of the conductive polymer (P3BT or P3HT) and an insulating polymer (PMMA) was used, from which the polymer nanolayers on substrates of different surface energy (silicon, silan-functionalized silicon) were made, thereby modifying phase separation process. Topography of nanolayers was analyzed using atomic force microscopy and their morphology with use of fluorescence microscopy and secondary ion mass spectrometry. In addition, tests have shown that the selective adsorption of protein (bovine serum albumin (BSA)) to one of the polymers is possible for the columnar nanolayers

The Clinical Trial Landscape for Melanoma Therapies

(1) Despite many years of research, melanoma still remains a big challenge for modern medicine. The purpose of this article is to review publicly available clinical trials to find trends regarding the number of trials, their location, and interventions including the most frequently studied drugs and their combinations. (2) We surveyed clinical trials registered in the International Clinical Trials Registry Platform (ICTRP), one of the largest databases on clinical trials. The search was performed on 30 November 2018 using the term “melanoma”. Data have been supplemented with the information obtained from publicly available data repositories including PubMed, World Health Organization, National Cancer Institute, Centers for Disease Control and Prevention, European Cancer Information System, and many others to bring the historical context of this study. (3) Among the total of 2563 clinical trials included in the analysis, most have been registered in the USA (1487), which is 58% of the total. The most commonly studied drug in clinical trials was ipilimumab, described as applied intervention in 251 trials. (4) An increase in the number of melanoma clinical trials using immunomodulating monoclonal antibody therapies, small molecule-targeted therapies (inhibitors of BRAF, MEK, CDK4/6), and combination therapies is recognized. This illustrates the tendency towards precision medicine

Reduced internalization of ectosomes by hyperglycemic endothelial cells influences wound healing processes

Pęcherzyki zewnątrzkomórkowe, a zwłaszcza większe z nich - ektosomy są uważane za struktury odpowiedzialne za komunikację między komórkową. Mogą być one internalizowane przez komórki śródbłonka i za pośrednictwem zamkniętych w ich wnętrzu cząsteczek biologiczne aktywnych zmieniać zachowanie komórek docelowych. W warunkach hiperglikemii, komórki śródbłonka podlegają zmianom: dochodzi do ich sztywnienia, czy ograniczenia ruchomości, zmiany te objawiają się jako tzw. dysfunkcja komórek śródbłonka i przyczyniają się do powstania zmian w systemach krążenia mikro- i makronaczyniowego. Celem niniejszej pracy było zbadanie, czy ektosomy po ich internalizacji mogą przywrócić prawidłową ruchomość i zdolność do migracji komórek śródbłonka. W trakcie badań został zmierzony stopień internalizacji ektosomów przez komórki oraz wpływ ekrosomów na morfologię komórek śródbłonka, organizację cytoszkieletu oraz, z wykorzystaniem mikroskopii sił atomowych, sztywność błony komórkowej. Dodatkowo, aby ocenić jak hiperglikemia i ektosomy wpływają na ekspersję genów przeprowadziliśmy analizę transkryptomiczną. Nasze badania pokazały, że internalizacja ektosomów do komórek śródbłonka jest upośledzona w warunkach hiperglikemii. Dodatkowo komórki hodowane w hiperglikemii mają większy rozmiar, sztywniejszą powierzchnię oraz gęstszy cytoszkielet niż komórki hodowane w prawidłowej glikemii. Zaobserwowaliśmy również, że zmiany ekspresji w wielu szlakach komórkowych, zwłaszcza tych odpowiedzialnych za transport wewnątrzkomórkowy, metabolizm i organizację komponentów wewnątrzkomórkowych. Pokazaliśmy również, że sama stymulacja prawidłowymi ektosomami komórek hodowanych w warunkach hiperglikemicznych nie może odwrócić tych niekorzystnych zmian.Extracellular vesicles, namely those larger ones - Ectosomes (Ect), are thought to be important cell-to-cell communication medium. They can be internalized by endothelial cells, owing to their cargo, can modulate targeted cell behavior. Under hyperglycemic conditions (HGC), endothelial cells change their properties and became stiffer and less mobile which causes endothelial dysfunction and abnormalities in micro- and macrovascular system. The aim of this study was to find whether Ect restore mobility and motility of macrovascular endothelial cells under HGC. Uptake of Ect, cell morphology, cytoskeleton organization and membrane stiffness (by atomic force microscopy) were analyzed after the exposure to isolated Ect. To find which cellular pathways were deregulated by HGC and how Ect restore gene expression profile, transcriptome analysis was done. We observed that endothelial cells internalized more Ect under normoglycemic conditions (NGC) then HGC. Hyperglycemic cells (HG) were bigger and showed the stiffer surface with denser actin cytoskeleton in comparison to normoclycemic cells. Number of metabolic pathways was influenced under HGC, especially those related to intracellular transport, metabolism and cellular component organization and Ect did not restore HGC impaired cell signaling. Ectosomes cannot reverse this harmful effect of hyperglyceemia in endothelial cells, which can have clinical implication in use Ect as therapeutic target in diabetes treatment