scholarly journals EORNA, a barley gene and transcript abundance database

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Linda Milne ◽  
Micha Bayer ◽  
Paulo Rapazote-Flores ◽  
Claus-Dieter Mayer ◽  
Robbie Waugh ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Transcript Abundance ◽  
Specific Gene ◽  
Rna Seq ◽  
Scottish Gaelic ◽  
On Demand ◽  
Abundance Data ◽  
Reference Transcript ◽  
Abundance Variation ◽  
Meta Analyses

AbstractA high-quality, barley gene reference transcript dataset (BaRTv1.0), was used to quantify gene and transcript abundances from 22 RNA-seq experiments, covering 843 separate samples. Using the abundance data we developed a Barley Expression Database (EORNA*) to underpin a visualisation tool that displays comparative gene and transcript abundance data on demand as transcripts per million (TPM) across all samples and all the genes. EORNA provides gene and transcript models for all of the transcripts contained in BaRTV1.0, and these can be conveniently identified through either BaRT or HORVU gene names, or by direct BLAST of query sequences. Browsing the quantification data reveals cultivar, tissue and condition specific gene expression and shows changes in the proportions of individual transcripts that have arisen via alternative splicing. TPM values can be easily extracted to allow users to determine the statistical significance of observed transcript abundance variation among samples or perform meta analyses on multiple RNA-seq experiments. * Eòrna is the Scottish Gaelic word for Barley.

scholarly journals EoRNA, a barley gene and transcript abundance database

2020 ◽  
Author(s):  
Linda Milne ◽  
Micha Bayer ◽  
Paulo Rapazote-Flores ◽  
Claus-Dieter Mayer ◽  
Robbie Waugh ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Transcript Abundance ◽  
Specific Gene ◽  
Rna Seq ◽  
Scottish Gaelic ◽  
On Demand ◽  
Abundance Data ◽  
Reference Transcript ◽  
Abundance Variation ◽  
Meta Analyses

AbstractA high-quality, barley gene reference transcript dataset (BaRTv1.0), was used to quantify gene and transcript abundances from 22 RNA-seq experiments, covering 843 separate samples. Using the abundance data we developed a Barley Expression Database (EoRNA* – Expression of RNA) to underpin a visualisation tool that displays comparative gene and transcript abundance data on demand as transcripts per million (TPM) across all samples and all the genes. EoRNA provides gene and transcript models for all of the transcripts contained in BaRTV1.0, and these can be conveniently identified through either BaRT or HORVU gene names, or by direct BLAST of query sequences. Browsing the quantification data reveals cultivar, tissue and condition specific gene expression and shows changes in the proportions of individual transcripts that have arisen via alternative splicing. TPM values can be easily extracted to allow users to determine the statistical significance of observed transcript abundance variation among samples or perform meta analyses on multiple RNA-seq experiments. * Eòrna is the Scottish Gaelic word for Barley

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

scholarly journals A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Xiaoqiang Zhu ◽  
Xianglong Tian ◽  
Linhua Ji ◽  
Xinyu Zhang ◽  
Yingying Cao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Drug Sensitivity ◽  
Chemotherapy Resistance ◽  
Gene Expression Signature ◽  
Prediction Algorithm ◽  
Specific Gene ◽  
Chemotherapy Response ◽  
Rna Seq ◽  
Mesenchymal Transition

AbstractStudies have shown that tumor microenvironment (TME) might affect drug sensitivity and the classification of colorectal cancer (CRC). Using TME-specific gene signature to identify CRC subtypes with distinctive clinical relevance has not yet been tested. A total of 18 “bulk” RNA-seq datasets (total n = 2269) and four single-cell RNA-seq datasets were included in this study. We constructed a “Signature associated with FOLFIRI resistant and Microenvironment” (SFM) that could discriminate both TME and drug sensitivity. Further, SFM subtypes were identified using K-means clustering and verified in three independent cohorts. Nearest template prediction algorithm was used to predict drug response. TME estimation was performed by CIBERSORT and microenvironment cell populations-counter (MCP-counter) methods. We identified six SFM subtypes based on SFM signature that discriminated both TME and drug sensitivity. The SFM subtypes were associated with distinct clinicopathological, molecular and phenotypic characteristics, specific enrichments of gene signatures, signaling pathways, prognosis, gut microbiome patterns, and tumor lymphocytes infiltration. Among them, SFM-C and -F were immune suppressive. SFM-F had higher stromal fraction with epithelial-to-mesenchymal transition phenotype, while SFM-C was characterized as microsatellite instability phenotype which was responsive to immunotherapy. SFM-D, -E, and -F were sensitive to FOLFIRI and FOLFOX, while SFM-A, -B, and -C were responsive to EGFR inhibitors. Finally, SFM subtypes had strong prognostic value in which SFM-E and -F had worse survival than other subtypes. SFM subtypes enable the stratification of CRC with potential chemotherapy response thereby providing more precise therapeutic options for these patients.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Lago ◽  
Matteo Nadai ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

scholarly journals Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Perrine Janiaud ◽  
Arnav Agarwal ◽  
Ioanna Tzoulaki ◽  
Evropi Theodoratou ◽  
Konstantinos K. Tsilidis ◽  
...  
Keyword(s):  
Protective Factors ◽  
Observational Studies ◽  
Prediction Interval ◽  
Statistical Significance ◽  
Median Number ◽  
Small Study ◽  
Study Heterogeneity ◽  
Large Heterogeneity ◽  
Meta Analyses ◽  
No Gold Standard

Abstract Background The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. Methods We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10−6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance. Results 3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10−6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in observational studies, 37.1% had effect estimates in opposite directions and 43.5% had effect estimates differing beyond chance in the two designs. Across 94 comparisons assessed in both MR and observational studies, such discrepancies occurred in 30.8% and 54.7%, respectively. Conclusions Acknowledging that no gold-standard exists to judge whether an observational association is genuine, statistically significant results are common in observational studies, but they are rarely convincing or corroborated by randomized evidence.

scholarly journals Neuromuscular junction-specific genes screening by deep RNA-seq analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiankun Hui ◽  
Hongyang Jing ◽  
Xinsheng Lai
Keyword(s):  
Ion Channel ◽  
Neuromuscular Junctions ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Muscle Membrane ◽  
Receptor Interaction ◽  
Specific Gene ◽  
Rna Seq ◽  
Channel Activity ◽  
Ppi Networks

Abstract Background Neuromuscular junctions (NMJs) are chemical synapses formed between motor neurons and skeletal muscle fibers and are essential for controlling muscle contraction. NMJ dysfunction causes motor disorders, muscle wasting, and even breathing difficulties. Increasing evidence suggests that many NMJ disorders are closely related to alterations in specific gene products that are highly concentrated in the synaptic region of the muscle. However, many of these proteins are still undiscovered. Thus, screening for NMJ-specific proteins is essential for studying NMJ and the pathogenesis of NMJ diseases. Results In this study, synaptic regions (SRs) and nonsynaptic regions (NSRs) of diaphragm samples from newborn (P0) and adult (3-month-old) mice were used for RNA-seq. A total of 92 and 182 genes were identified as differentially expressed between the SR and NSR in newborn and adult mice, respectively. Meanwhile, a total of 1563 genes were identified as differentially expressed between the newborn SR and adult SR. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) of the DEGs were performed. Protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape. Further analysis identified some novel proteins and pathways that may be important for NMJ development, maintenance and maturation. Specifically, Sv2b, Ptgir, Gabrb3, P2rx3, Dlgap1 and Rims1 may play roles in NMJ development. Hcn1 may localize to the muscle membrane to regulate NMJ maintenance. Trim63, Fbxo32 and several Asb family proteins may regulate muscle developmental-related processes. Conclusion Here, we present a complete dataset describing the spatiotemporal transcriptome changes in synaptic genes and important synaptic pathways. The neuronal projection-related pathway, ion channel activity and neuroactive ligand-receptor interaction pathway are important for NMJ development. The myelination and voltage-gated ion channel activity pathway may be important for NMJ maintenance. These data will facilitate the understanding of the molecular mechanisms underlying the development and maintenance of NMJ and the pathogenesis of NMJ disorders.

scholarly journals Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mathys Grapotte ◽  
Manu Saraswat ◽  
Chloé Bessière ◽  
Christophe Menichelli ◽  
Jordan A. Ramilowski ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Tandem Repeats ◽  
Specific Gene ◽  
Rna Seq ◽  
Transcription Start Sites ◽  
Long Read ◽  
Cap Analysis ◽  
Dna Tandem Repeats ◽  
Short Tandem ◽  
Str Polymorphism

AbstractUsing the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.

scholarly journals A Meta-Analysis of Brain-Derived Neurotrophic Factor Effects on Brain Volume in Schizophrenia: Genotype and Serum Levels

2021 ◽  
pp. 1-14
Author(s):  
Anthony O. Ahmed ◽  
Samantha Kramer ◽  
Naama Hofman ◽  
John Flynn ◽  
Marie Hansen ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Psychotic Disorders ◽  
Brain Volume ◽  
Statistical Significance ◽  
Brain Derived Neurotrophic Factor ◽  
Volume Data ◽  
Analytic Review ◽  
Volume Measurements ◽  
Meta Analyses ◽  
Serum Bdnf

Aim: The Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene has established pleiotropic effects on schizophrenia incidence and morphologic alterations in the illness. The effects of brain-derived neurotrophic factor (BDNF) on brain volume measurements are however mixed seeming to be less established for most brain regions. The current meta-analytic review examined (1) the association of the Val66Met SNP and brain volume alterations in schizophrenia by comparing Met allele carriers to Val/Val homozygotes and (2) the association of serum BDNF with brain volume measurements. Method: Studies included in the meta-analyses were identified through an electronic search of PubMed and PsycInfo (via EBSCO) for English language publications from January 2000 through December 2017. Included studies had conducted a genotyping procedure of Val66Met or obtained assays of serum BDNF and obtained brain volume data in patients with psychotic disorders. Nonhuman studies were excluded. Results: Study 1 which included 52 comparisons of Met carriers and Val/Val homozygotes found evidence of lower right and left hippocampal volumes among Met allele carriers with schizophrenia. Frontal measurements, while also lower among Met carriers, did not achieve statistical significance. Study 2 which included 7 examinations of the correlation between serum BDNF and brain volume found significant associations between serum BDNF levels and right and left hippocampal volume with lower BDNF corresponding to lower volumes. Discussion: The meta-analyses provided evidence of associations between brain volume alterations in schizophrenia and variations on the Val66Met SNP and serum BDNF. Given the limited number of studies, it remains unclear if BDNF effects are global or regionally specific.

scholarly journals Zea mays RNA-seq estimated transcript abundances are strongly affected by read mapping bias

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuhua Zhan ◽  
Cortland Griswold ◽  
Lewis Lukens
Keyword(s):  
Gene Expression ◽  
Zea Mays ◽  
Reference Genome ◽  
Transcript Abundance ◽  
Gene Transcript ◽  
Rna Seq ◽  
Individual Genome ◽  
Abundance Estimates ◽  
Mapping Bias ◽  
Quantify Gene Expression

Abstract Background Genetic variation for gene expression is a source of phenotypic variation for natural and agricultural species. The common approach to map and to quantify gene expression from genetically distinct individuals is to assign their RNA-seq reads to a single reference genome. However, RNA-seq reads from alleles dissimilar to this reference genome may fail to map correctly, causing transcript levels to be underestimated. Presently, the extent of this mapping problem is not clear, particularly in highly diverse species. We investigated if mapping bias occurred and if chromosomal features associated with mapping bias. Zea mays presents a model species to assess these questions, given it has genotypically distinct and well-studied genetic lines. Results In Zea mays, the inbred B73 genome is the standard reference genome and template for RNA-seq read assignments. In the absence of mapping bias, B73 and a second inbred line, Mo17, would each have an approximately equal number of regulatory alleles that increase gene expression. Remarkably, Mo17 had 2–4 times fewer such positively acting alleles than did B73 when RNA-seq reads were aligned to the B73 reference genome. Reciprocally, over one-half of the B73 alleles that increased gene expression were not detected when reads were aligned to the Mo17 genome template. Genes at dissimilar chromosomal ends were strongly affected by mapping bias, and genes at more similar pericentromeric regions were less affected. Biased transcript estimates were higher in untranslated regions and lower in splice junctions. Bias occurred across software and alignment parameters. Conclusions Mapping bias very strongly affects gene transcript abundance estimates in maize, and bias varies across chromosomal features. Individual genome or transcriptome templates are likely necessary for accurate transcript estimation across genetically variable individuals in maize and other species.

Antibiotic Prophylaxis in Acute Necrotizing Pancreatitis Revisited

2009 ◽  
Vol 43 (9) ◽  
pp. 1486-1495 ◽  
Author(s):  
Marisel Segarra-Newnham ◽  
Augustus Hough
Keyword(s):  
Intensive Care ◽  
Antibiotic Prophylaxis ◽  
Randomized Trials ◽  
Necrotizing Pancreatitis ◽  
Acute Necrotizing Pancreatitis ◽  
On Demand ◽  
Previous Review ◽  
Significant Difference ◽  
Acute Necrotizing ◽  
Meta Analyses

Objective: To review studies of antibiotic prophylaxis in acute necrotizing pancreatitis published in the last decade and update recommendations. Data Sources: A search of PubMed (1998–July 2009) was conducted using the terms necrotizing pancreatitis, antibiotics, prophylaxis, and treatment. Clinical studies, meta-analyses, and review articles published in English were included. Additional references were obtained from article bibliographies. Randomized trials published before 1998 were included if indicated. Study Selection and Data Extraction: Relevant studies or meta-analyses on antibiotic prophylaxis since our previous review in 1998 were evaluated; older data were included if still relevant. Data Synthesis: Since our previous review, 4 more randomized trials, including 2 double-blind trials, have been conducted. The blinded studies found no significant difference in mortality with antibiotic prophylaxis compared with placebo, while the unblinded studies found a significant decrease in infections. Given these disparate results, available guidelines and meta-analyses provide different conclusions, usually based on exclusion or inclusion of a single trial. Based on all available data, antibiotic prophylaxis should not be used in patients with necrotizing pancreatitis. Instead, a more measured, on-demand use of antibiotics is preferred. Antibiotics should be added if signs and symptoms of infection are present (eg, fever, leukocytosis, positive results of cultures). Given improvements in intensive care and nutritional support, recent trials have found a lower incidence of infected necrotizing pancreatitis than before. Therefore, future trials are likely to need higher numbers of patients. Conclusions: Use of antibiotic prophylaxis for patients with necrotizing pancreatitis is not indicated, based on 2 blinded trials. Instead, on-demand use of antibiotics appears to be appropriate. Given progress in intensive care and the high crossover rate in studies, the need for antibiotic prophylaxis may continue to be debated for decades.

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