Pathway Figure OCR (PFOCR) is a novel kind of pathway database approaching the breadth and depth of Gene Ontology while providing rich, mechanistic diagrams and direct literature support. Here, we ...highlight the utility of PFOCR in disease research in comparison with popular pathway databases through an assessment of disease coverage and analytical applications. In addition to common pathway analysis use cases, we present two advanced case studies demonstrating unique advantages of PFOCR in terms of cancer subtype and grade prediction analyses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The genotyping‐by‐sequencing (GBS) approach was applied to genotype selected interspecific hybrid (F1) and backcross (BC2) families of Elaeis oleifera and Elaeis guineensis. Genome‐wide linkage ...disequilibrium (LD) was estimated at 150‐kb pairwise distance for r2 values of 0.17 and 0.42 for F1 and BC2, respectively. Single marker‐trait association analysis identified 47 markers associated with five fatty acid composition (FAC) traits (C16:0, C18:0, C18:1, C18:2 and iodine value IV) in F1, and 12 significant markers linked to oleic acid (C18:1) and vegetative traits (petiole width and mean leaf width) in BC. Within the QTL region associated with FAC traits, we identified key candidate genes influencing fatty acid synthesis. We implemented two machine learning algorithms, namely random forest and gradient boosting, to evaluate the ability of significant markers in predicting phenotype values. We also demonstrated the contribution of different marker combinations on trait values via prediction trees. This is the first attempt to evaluate the predictive ability of a combination of markers associated with traits identified from association mapping analysis in oil palm populations.
Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and ...indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Using a microscopy-based binding assay, we show that K-Ras, H-Ras, and five homologous Ras family small GTPases function upstream of PI3K by directly binding the PI3K catalytic subunit, p110. In contrast, several Rho family small GTPases activated PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities. Thus, a distributed network of Ras and Rho family small GTPases induces and reinforces PI3K activity, explaining past challenges to elucidate the specific relevance of different small GTPases in regulating PI3K and controlling cell polarization and chemotaxis.
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► Twenty-one small GTPases activate the PI3K pathway ► Upstream small GTPases activate PI3K via direct interaction ► Cooperation of downstream small GTPases is required for effective activation of PI3K
Due to increasing demand for new advanced crops, considerable efforts have been made to explore the improvement of stress and disease resistance cultivar traits through the study of wild crops. When ...both wild and interspecific hybrid materials are available, a common approach has been to study two types of materials separately and simply compare the quantitative trait locus (QTL) regions. However, combining the two types of materials can potentially create a more efficient method of finding predictive QTLs. In this simulation study, we focused on scenarios involving causal marker expression suppressed by
trans-
regulatory mechanisms, where the otherwise easily lost associated signals benefit the most from combining the two types of data. A probabilistic sampling approach was used to prioritize consistent genotypic phenotypic patterns across both types of data sets. We chose random forest and gradient boosting to apply the prioritization scheme and found that both facilitated the investigation of predictive causal markers in most of the biological scenarios simulated.
Blood protein extravasation through a disrupted blood-brain barrier and innate immune activation are hallmarks of neurological diseases and emerging therapeutic targets. However, how blood proteins ...polarize innate immune cells remains largely unknown. Here, we established an unbiased blood-innate immunity multiomic and genetic loss-of-function pipeline to define the transcriptome and global phosphoproteome of blood-induced innate immune polarization and its role in microglia neurotoxicity. Blood induced widespread microglial transcriptional changes, including changes involving oxidative stress and neurodegenerative genes. Comparative functional multiomics showed that blood proteins induce distinct receptor-mediated transcriptional programs in microglia and macrophages, such as redox, type I interferon and lymphocyte recruitment. Deletion of the blood coagulation factor fibrinogen largely reversed blood-induced microglia neurodegenerative signatures. Genetic elimination of the fibrinogen-binding motif to CD11b in Alzheimer's disease mice reduced microglial lipid metabolism and neurodegenerative signatures that were shared with autoimmune-driven neuroinflammation in multiple sclerosis mice. Our data provide an interactive resource for investigation of the immunology of blood proteins that could support therapeutic targeting of microglia activation by immune and vascular signals.
Endometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune ...lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single-cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages.
A case-control study was designed. Endometrial biopsies and blood (n = 60 total) were obtained from women with (n = 20, n = 17, respectively) and without (n = 14, n = 9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed: one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed.
The broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91
macrophages overexpressed SIRPα (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease.
A greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Crop wild relatives are a reservoir of phenotypic variation not present in the germplasm of cultivated species and thus have great potential for crop improvement. However, issues of genetic ...compatibility often interfere with effective utilization of crop wild relative taxa. Among chickpea (Cicer arietinum L.) crop wild relatives, Cicer echinospermum P.H. Davis is the sole species in the secondary genepool, being partially compatible with the primary genepool that is composed of the cultigen and its progenitor wild species Cicer reticulatum Ladizinksy. We report results from genetic studies among interspecific hybrids between cultivated chickpea and accessions from six recently identified wild C. echinospermum sites in southeastern Turkey, encompassing the known genetic diversity of the secondary genepool. Our studies indicate that both hybrid sterility and hybrid breakdown occur and are associated with distinct subgroups of C. echinospermum. Analysis of early‐generation progenies suggests that both hybrid sterility and hybrid breakdown are conditioned by one to few genetic loci. These results clarify ambiguity in the nature of the hybridization barriers of reduced fertility in interspecific crossing of cultivated chickpea with C. echinospermum and should foster a more systematic and wider use of C. echinospermum for base broadening of cultivated chickpea.
Nonalcoholic fatty liver disease (NAFLD) is a well-recognized hepatic manifestation of metabolic disease in adults and has been associated with the development of gestational diabetes (GDM). Hepatic ...insulin resistance can result in increased release of glucose (from gluconeogenesis) and free fatty acids (due to enhanced lipolysis), which can lead in turn to fetal overgrowth. However, the relationship between maternal metabolic factors (such as circulating levels of triglycerides, free fatty acids FFA, or adipokines) and excessive fetal birthweight in NAFLD has not been carefully examined. In this study, we evaluated the relationship between NAFLD and the subsequent risk of large-for-gestational-age (LGA) birthweight.
Singleton nondiabetic pregnant women were evaluated for the presence of fatty liver at 10-14 weeks of gestation by abdominal ultrasound. The degree of fatty liver was classified as Grade 0-3 steatosis. At the time of liver ultrasound, maternal blood was taken after fasting and measured for adiponectin and FFA. LGA was defined as birthweight >90th percentile for gestational age.
A total of 623 women were included in the analysis. The frequency of LGA was 10.9% (68/623), and the frequency of NAFLD was 18.9%. The risk of LGA increased significantly in patients with Grade 2-3 steatosis in the first trimester. The relationship between Grade 2-3 steatosis and LGA remained significant after adjustment for maternal age, pre-pregnancy BMI, GDM, and maternal serum triglyceride levels. The concentration of maternal blood adiponectin at 10-14 weeks was significantly lower in cases with LGA than non-LGA, but the maternal blood FFA concentrations were not different between the groups.
The presence of Grade 2-3 steatosis on ultrasound in early pregnancy was associated with the increased risk of delivering an LGA infant, even after adjustment for multiple confounding factors including GDM. Adiponectin may be the linking biomarker between NAFLD and LGA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The explosive growth of genomic data provides an opportunity to make increased use of sequence variations for phenotype prediction. We have developed a prediction machine for quantitative phenotypes ...(WhoGEM) that overcomes some of the bottlenecks limiting the current methods. We demonstrated its performance by predicting quantitative disease resistance and quantitative functional traits in the wild model plant species, Medicago truncatula, using geographical locations as covariates for admixture analysis. The method's prediction reliability equals or outperforms all existing algorithms for quantitative phenotype prediction. WhoGEM analysis produces evidence that variation in genome admixture proportions explains most of the phenotypic variation for quantitative phenotypes.
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