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Previous studies have suggested that certain variants in immune-related genes may participate in the pathogenesis of multiple sclerosis (MS), including rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, rs16944 in the IL-1ß gene, rs2243250 in the IL-4 gene, and rs12722489 and rs2104286 in the IL-2Rα gene. However, the results remained inconclusive and conflicting. In view of this, a comprehensive meta-analysis including all eligible studies was conducted to investigate the association between these 8 selected genetic variants and MS risk. Up to June 2023, 64 related studies were finally included in this meta-analysis. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated by the random-effects model were used to evaluate the strength of association. Publication bias test, sensitivity analyses, and trial sequential analysis (TSA) were conducted to examine the reliability of statistical results. Our results indicated that rs17824933 in the CD6 gene, rs1883832 in the CD40 gene, rs2300747 in the CD58 gene, rs763361 in the CD226 gene, and rs12722489 and rs2104286 in the IL-2Rα gene may serve as the susceptible factors for MS pathogenesis, while rs16944 in the IL-1ß gene and rs2243250 in the IL-4 gene may not be associated with MS risk. However, the present findings need to be confirmed and reinforced in future studies.
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Certain cancer types afflict female and male patients disproportionately. The reasons include differences in male/female physiology, effect of sex hormones, risk behavior, environmental exposures, and genetics of the sex chromosomes X and Y. Loss of Y (LOY) is common in peripheral blood cells in aging men, and this phenomenon is associated with several diseases. However, the frequency and role of LOY in tumors is little understood. Here, we present a comprehensive catalog of LOY in >5,000 primary tumors from male patients in the TCGA. We show that LOY rates vary by tumor type and provide evidence for LOY being either a passenger or driver event depending on context. LOY in uveal melanoma specifically is associated with age and survival and is an independent predictor of poor outcome. LOY creates common dependencies on DDX3X and EIF1AX in male cell lines, suggesting that LOY generates unique vulnerabilities that could be therapeutically exploited.
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Cadmium pollution in agricultural soil is a great threat to crop growth and human health. In this research, with 1%, 3% and 5% biochar applied to control soil cadmium pollution, melon was selected to be the experimental object for physiological detection and transcriptome analysis, through which we explored the mechanism of cadmium tolerance and biochar mitigating cadmium stress in muskmelon. Three set concentrations of biochar have a mitigative effect on muskmelon cadmium stress, and 5% biochar and 3% biochar respectively have the best and the worst alleviative effect. The alleviation of biochar to cadmium stress on muskmelon is primarily in the manner of inhibiting cadmium transfer, while the resistance of muskmelon to cadmium stress is through activating phenylpropanoid pathway and overexpressing stress related genes. Under cadmium treatment, 11 genes of the phenylpropane pathway and 19 stress-related genes including cytochrome P450 family protein genes and WRKY transcription factor genes were up-regulated, while 1%, 3%, 5% biochar addition significantly downregulated 3, 0, 7 phenylpropane pathway genes and 17, 5, 16 stress-related genes, respectively. Genes such as cytochrome P450 protein family genes, WRKY transcription factor genes, and annexin genes may play a key role in muskmelon's resistance to cadmium stress. The results show the key pathways and genes of cadmium stress resistance and the effect of different concentrations of biochar in alleviating cadmium stress, which provide a reference for the research of cadmium stress resistance in crops and the application of biochar in cadmium pollution in agricultural soil.
Assuntos
Cádmio , Poluentes do Solo , Humanos , Cádmio/toxicidade , Cádmio/análise , Transcriptoma , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Carvão Vegetal/farmacologia , Solo , Fatores de Transcrição , Sistema Enzimático do Citocromo P-450RESUMO
Symbioses between legumes and rhizobia require establishment of the plant-derived symbiosome membrane, which surrounds the rhizobia and accommodates the symbionts by providing an interface for nutrient and signal exchange. The host cytoskeleton and endomembrane trafficking systems play central roles in the formation of a functional symbiotic interface for rhizobia endosymbiosis; however, the underlying mechanisms remain largely unknown. Here we demonstrate that the nodulation-specific kinesin-like calmodulin-binding protein (nKCBP), a plant-specific microtubule-based kinesin motor, controls central vacuole morphogenesis in symbiotic cells in Medicago truncatula. Phylogenetic analysis further indicated that nKCBP duplication occurs solely in legumes of the clade that form symbiosomes. Knockout of nKCBP results in central vacuole deficiency, defective symbiosomes and abolished nitrogen fixation. nKCBP decorates linear particles along microtubules, and crosslinks microtubules with the actin cytoskeleton, to control central vacuole formation by modulating vacuolar vesicle fusion in symbiotic cells. Together, our findings reveal that rhizobia co-opted nKCBP to achieve symbiotic interface formation by regulating cytoskeletal assembly and central vacuole morphogenesis during nodule development.
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Medicago truncatula , Rhizobium , Rhizobium/fisiologia , Simbiose/fisiologia , Cinesinas/genética , Vacúolos/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Medicago truncatula/genética , Medicago truncatula/metabolismo , MorfogêneseRESUMO
BACKGROUND: Exogenous cDNA introduced into an experimental system, either intentionally or accidentally, can appear as added read coverage over that gene in next-generation sequencing libraries derived from this system. If not properly recognized and managed, this cross-contamination with exogenous signal can lead to incorrect interpretation of research results. Yet, this problem is not routinely addressed in current sequence processing pipelines. RESULTS: We present cDNA-detector, a computational tool to identify and remove exogenous cDNA contamination in DNA sequencing experiments. We demonstrate that cDNA-detector can identify cDNAs quickly and accurately from alignment files. A source inference step attempts to separate endogenous cDNAs (retrocopied genes) from potential cloned, exogenous cDNAs. cDNA-detector provides a mechanism to decontaminate the alignment from detected cDNAs. Simulation studies show that cDNA-detector is highly sensitive and specific, outperforming existing tools. We apply cDNA-detector to several highly-cited public databases (TCGA, ENCODE, NCBI SRA) and show that contaminant genes appear in sequencing experiments where they lead to incorrect coverage peak calls. CONCLUSIONS: cDNA-detector is a user-friendly and accurate tool to detect and remove cDNA detection in NGS libraries. This two-step design reduces the risk of true variant removal since it allows for manual review of candidates. We find that contamination with intentionally and accidentally introduced cDNAs is an underappreciated problem even in widely-used consortium datasets, where it can lead to spurious results. Our findings highlight the importance of sensitive detection and removal of contaminant cDNA from NGS libraries before downstream analysis.
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Sequenciamento de Nucleotídeos em Larga Escala , Simulação por Computador , DNA Complementar/genética , Biblioteca Gênica , Análise de Sequência de DNARESUMO
2-Fluoro-5-(trifluoromethyl)aniline was found to be a suitable monodentate transient directing group (MonoTDG) to enable Ru(II)-catalyzed intermolecular direct ortho-C(sp2)-H imidation of benzaldehydes. N-Tosyloxyphthalimide was used as an alternative azide-free amidation reagent to achieve high efficiency and good functional group tolerance. Moreover, the reaction could be enlarged to gram scale, and the amidated product could be readily converted into useful quinazoline and fused isoindolinone scaffolds by one-step derivatization.
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Legumes have evolved a symbiotic relationship with rhizobial bacteria and their roots form unique nitrogen-fixing organs called nodules. Studies have shown that abiotic and biotic stresses alter the profile of gene expression and transcript mobility in plants. However, little is known about the systemic transport of RNA between roots and shoots in response to rhizobial infection on a genome-wide scale during the formation of legume-rhizobia symbiosis. In our study, we found that two soybean (Glycine max) cultivars, Peking and Williams, show a high frequency of single nucleotide polymorphisms; this allowed us to characterize the origin and mobility of transcripts in hetero-grafts of these two cultivars. We identified 4,552 genes that produce mobile RNAs in soybean, and found that rhizobial infection triggers mass transport of mRNAs between shoots and roots at the early stage of nodulation. The majority of these mRNAs are of relatively low abundance and their transport occurs in a selective manner in soybean plants. Notably, the mRNAs that moved from shoots to roots at the early stage of nodulation were enriched in many nodule-related responsive processes. Moreover, the transcripts of many known symbiosis-related genes that are induced by rhizobial infection can move between shoots and roots. Our findings provide a deeper understanding of endogenous RNA transport in legume-rhizobia symbiotic processes.
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Glycine max/genética , Infecções/genética , Brotos de Planta/genética , RNA Mensageiro/metabolismo , Rhizobium/genética , Nódulos Radiculares de Plantas/genética , Sequência de Bases , Transporte Biológico , Regulação da Expressão Gênica de Plantas , Biblioteca Genômica , Geografia , Infecções/metabolismo , Nucleotídeos/química , Polimorfismo Genético , Rhizobium/metabolismo , SimbioseRESUMO
High-throughput technology has become a powerful approach for routine plant research. Interpreting the biological significance of high-throughput data has largely focused on the functional characterization of a large gene list or genomic loci that involves the following two aspects: the functions of the genes or loci and how they are regulated as a whole, i.e. searching for the upstream regulators. Traditional platforms for functional annotation largely help resolving the first issue. Addressing the second issue is essential for a global understanding of the regulatory mechanism, but is more challenging, and requires additional high-throughput experimental evidence and a unified statistical framework for data-mining. The rapid accumulation of 'omics data provides a large amount of experimental data. We here present Plant Regulomics, an interface that integrates 19 925 transcriptomic and epigenomic data sets and diverse sources of functional evidence (58 112 terms and 695 414 protein-protein interactions) from six plant species along with the orthologous genes from 56 whole-genome sequenced plant species. All pair-wise transcriptomic comparisons with biological significance within the same study were performed, and all epigenomic data were processed to genomic loci targeted by various factors. These data were well organized to gene modules and loci lists, which were further implemented into the same statistical framework. For any input gene list or genomic loci, Plant Regulomics retrieves the upstream factors, treatments, and experimental/environmental conditions regulating the input from the integrated 'omics data. Additionally, multiple tools and an interactive visualization are available through a user-friendly web interface. Plant Regulomics is available at http://bioinfo.sibs.ac.cn/plant-regulomics.
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Bases de Dados Genéticas , Genoma de Planta/genética , Plantas/genética , Plantas/metabolismo , Genômica , Software , Transcriptoma/genéticaRESUMO
The phytohormone abscisic acid (ABA)-induced leaf senescence facilitates nutrient reuse and potentially contributes to enhancing plant stress tolerance. However, excessive senescence causes serious reductions in crop yield, and the mechanism by which senescence is finely tuned at different levels is still insufficiently understood. Here, we found that the double mutant of core enzymes of the polycomb repressive complex 2 (PRC2) is hypersensitive to ABA in Arabidopsis thaliana. To elucidate the interplay between ABA and PRC2 at the genome level, we extensively profiled the transcriptomic and epigenomic changes triggered by ABA. We observed that H3K27me3 preferentially targets ABA-induced senescence-associated genes (SAGs). In the double, but not single, mutant of PRC2 enzymes, these SAGs were derepressed and could be more highly induced by ABA compared with the wild-type, suggesting a redundant role for the PRC2 enzymes in negatively regulating ABA-induced senescence. Contrary to the rapid transcriptomic changes triggered by ABA, the reduction of H3K27me3 at these SAGs falls far behind the induction of their expression, indicating that PRC2-mediated H3K27me3 contributed to long-term damping of ABA-induced senescence to prevent an oversensitive response. The findings of this study may serve as a paradigm for a global understanding of the interplay between the rapid effects of a phytohormone such as ABA and the long-term effects of the epigenetic machinery in regulating plant senescence processes and environmental responses.
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Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas Repressoras/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Epigênese Genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Complexo Repressor Polycomb 2 , Proteínas Repressoras/genética , Estresse Fisiológico , Fatores de Tempo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Genetic diversity in plants is remarkably high. Recent whole genome sequencing (WGS) of 67 rice accessions recovered 10,872 novel genes. Comparison of the genetic architecture among divergent populations or between crops and wild relatives is essential for obtaining functional components determining crucial traits. However, many major crops have gigabase-scale genomes, which are not well-suited to WGS. Existing cost-effective sequencing approaches including re-sequencing, exome-sequencing and restriction enzyme-based methods all have difficulty in obtaining long novel genomic sequences from highly divergent population with large genome size. The present study presented a reference-independent core genome targeted sequencing approach, CGT-seq, which employed epigenomic information from both active and repressive epigenetic marks to guide the assembly of the core genome mainly composed of promoter and intragenic regions. This method was relatively easily implemented, and displayed high sensitivity and specificity for capturing the core genome of bread wheat. 95% intragenic and 89% promoter region from wheat were covered by CGT-seq read. We further demonstrated in rice that CGT-seq captured hundreds of novel genes and regulatory sequences from a previously unsequenced ecotype. Together, with specific enrichment and sequencing of regions within and nearby genes, CGT-seq is a time- and resource-effective approach to profiling functionally relevant regions in sequenced and non-sequenced populations with large genomes.
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Epigênese Genética/fisiologia , Epigenômica/métodos , Especiação Genética , Variação Genética/genética , Tamanho do Genoma/fisiologia , Sequenciamento Completo do Genoma/métodos , Biologia Computacional/métodos , Genoma/genética , Técnicas de Genotipagem/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Anotação de Sequência Molecular/métodos , Oryza/classificação , Oryza/genética , Análise de Sequência de DNA/métodos , Transcriptoma , Triticum/classificação , Triticum/genéticaRESUMO
Phytohormones regulate diverse aspects of plant growth and environmental responses. Recent high-throughput technologies have promoted a more comprehensive profiling of genes regulated by different hormones. However, these omics data generally result in large gene lists that make it challenging to interpret the data and extract insights into biological significance. With the rapid accumulation of theses large-scale experiments, especially the transcriptomic data available in public databases, a means of using this information to explore the transcriptional networks is needed. Different platforms have different architectures and designs, and even similar studies using the same platform may obtain data with large variances because of the highly dynamic and flexible effects of plant hormones; this makes it difficult to make comparisons across different studies and platforms. Here, we present a web server providing gene set-level analyses of Arabidopsis thaliana hormone responses. GSHR collected 333 RNA-seq and 1,205 microarray datasets from the Gene Expression Omnibus, characterizing transcriptomic changes in Arabidopsis in response to phytohormones including abscisic acid, auxin, brassinosteroids, cytokinins, ethylene, gibberellins, jasmonic acid, salicylic acid, and strigolactones. These data were further processed and organized into 1,368 gene sets regulated by different hormones or hormone-related factors. By comparing input gene lists to these gene sets, GSHR helped to identify gene sets from the input gene list regulated by different phytohormones or related factors. Together, GSHR links prior information regarding transcriptomic changes induced by hormones and related factors to newly generated data and facilities cross-study and cross-platform comparisons; this helps facilitate the mining of biologically significant information from large-scale datasets. The GSHR is freely available at http://bioinfo.sibs.ac.cn/GSHR/.
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In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice (Oryza sativa) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 (WOX11) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.
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High-throughput technology is gradually becoming a powerful tool for routine research in rice. Interpretation of biological significance from the huge amount of data is a critical but non-trivial task, especially for rice, for which gene annotations rely heavily on sequence similarity rather than direct experimental evidence. Here we describe the annotation platform for comprehensive annotation of rice multi-omics data (CARMO), which provides multiple web-based analysis tools for in-depth data mining and visualization. The central idea involves systematic integration of 1819 samples from omics studies and diverse sources of functional evidence (15 401 terms), which are further organized into gene sets and higher-level gene modules. In this way, the high-throughput data may easily be compared across studies and platforms, and integration of multiple types of evidence allows biological interpretation from the level of gene functional modules with high confidence. In addition, the functions and pathways for thousands of genes lacking description or validation may be deduced based on concerted expression of genes within the constructed co-expression networks or gene modules. Overall, CARMO provides comprehensive annotations for transcriptomic datasets, epi-genomic modification sites, single nucleotide polymorphisms identified from genome re-sequencing, and the large gene lists derived from these omics studies. Well-organized results, as well as multiple tools for interactive visualization, are available through a user-friendly web interface. Finally, we illustrate how CARMO enables biological insights using four examples, demonstrating that CARMO is a highly useful resource for intensive data mining and hypothesis generation based on rice multi-omics data. CARMO is freely available online (http://bioinfo.sibs.ac.cn/carmo).