RESUMEN
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.
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Secuenciación de Inmunoprecipitación de Cromatina , Cromatina , Bases de Datos Genéticas , Análisis de la Célula Individual , Cromatina/genética , Epigénesis Genética , Humanos , AnimalesRESUMEN
Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.
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Elementos de Facilitación Genéticos , Redes Reguladoras de Genes , Programas Informáticos , Factores de Transcripción , Animales , Humanos , Ratones , Regulación de la Expresión Génica , Genómica , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The rapid development of genomic high-throughput sequencing has identified a large number of DNA regulatory elements with abundant epigenetics markers, which promotes the rapid accumulation of functional genomic region data. The comprehensively understanding and research of human functional genomic regions is still a relatively urgent work at present. However, the existing analysis tools lack extensive annotation and enrichment analytical abilities for these regions. Here, we designed a novel software, Genomic Region sets Enrichment Analysis Platform (GREAP), which provides comprehensive region annotation and enrichment analysis capabilities. Currently, GREAP supports 85 370 genomic region reference sets, which cover 634 681 107 regions across 11 different data types, including super enhancers, transcription factors, accessible chromatins, etc. GREAP provides widespread annotation and enrichment analysis of genomic regions. To reflect the significance of enrichment analysis, we used the hypergeometric test and also provided a Locus Overlap Analysis. In summary, GREAP is a powerful platform that provides many types of genomic region sets for users and supports genomic region annotations and enrichment analyses. In addition, we developed a customizable genome browser containing >400 000 000 customizable tracks for visualization. The platform is freely available at http://www.liclab.net/Greap/view/index.
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Genómica , Programas Informáticos , Cromatina , Genoma Humano , Humanos , Anotación de Secuencia Molecular , Factores de TranscripciónRESUMEN
MOTIVATION: DNA methylation within gene body and promoters in cancer cells is well documented. An increasing number of studies showed that cytosine-phosphate-guanine (CpG) sites falling within other regulatory elements could also regulate target gene activation, mainly by affecting transcription factors (TFs) binding in human cancers. This led to the urgent need for comprehensively and effectively collecting distinct cis-regulatory elements and TF-binding sites (TFBS) to annotate DNA methylation regulation. RESULTS: We developed a database (CanMethdb, http://meth.liclab.net/CanMethdb/) that focused on the upstream and downstream annotations for CpG-genes in cancers. This included upstream cis-regulatory elements, especially those involving distal regions to genes, and TFBS annotations for the CpGs and downstream functional annotations for the target genes, computed through integrating abundant DNA methylation and gene expression profiles in diverse cancers. Users could inquire CpG-target gene pairs for a cancer type through inputting a genomic region, a CpG, a gene name, or select hypo/hypermethylated CpG sets. The current version of CanMethdb documented a total of 38 986 060 CpG-target gene pairs (with 6 769 130 unique pairs), involving 385 217 CpGs and 18 044 target genes, abundant cis-regulatory elements and TFs for 33 TCGA cancer types. CanMethdb might help biologists perform in-depth studies of target gene regulations based on DNA methylations in cancer. AVAILABILITY AND IMPLEMENTATION: The main program is available at https://github.com/chunquanlipathway/CanMethdb. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Metilación de ADN , Neoplasias , Humanos , Factores de Transcripción/metabolismo , Genoma , Secuencias Reguladoras de Ácidos Nucleicos , Regiones Promotoras Genéticas , Neoplasias/genética , ADN/metabolismo , Islas de CpGRESUMEN
BACKGROUND: Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC. METHODS: The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan-Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. RESULTS: Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P < 0.001). TET2+5hmC+ (high TET2 and high 5hmC) association was significantly associated with well differentiation, myometrial invasion, negative lymph node metastasis, and tumor stage in EC. Association of TET2 and 5hmC was confirmed as a prognostic factor (HR = 2.843, 95%CI = 1.226-3.605, P = 0.007) for EC patients, and EC patients with TET2-5hmC- level had poor overall survival. CONCLUSIONS: In summary, the association of TET2 and 5hmC was downregulated in EC tissues, and may be a potential poor prognostic indicator for EC patients. Combined detection of TET2 and 5hmC may be valuable for the diagnosis and prognosis of EC.
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5-Metilcitosina , Carcinoma Endometrioide , Dioxigenasas , Neoplasias Endometriales , Femenino , Humanos , 5-Metilcitosina/análogos & derivados , Carcinoma Endometrioide/genética , Relevancia Clínica , Dioxigenasas/genética , Dioxigenasas/metabolismo , Metilación de ADN , Proteínas de Unión al ADNRESUMEN
Transcription factors (TFs) play key roles in biological processes and are usually used as cell markers. The emerging importance of TFs and related markers in identifying specific cell types in human diseases increases the need for a comprehensive collection of human TFs and related markers sets. Here, we developed the TF-Marker database (TF-Marker, http://bio.liclab.net/TF-Marker/), aiming to provide cell/tissue-specific TFs and related markers for human. By manually curating thousands of published literature, 5905 entries including information about TFs and related markers were classified into five types according to their functions: (i) TF: TFs which regulate expression of the markers; (ii) T Marker: markers which are regulated by the TF; (iii) I Marker: markers which influence the activity of TFs; (iv) TFMarker: TFs which play roles as markers and (v) TF Pmarker: TFs which play roles as potential markers. The 5905 entries of TF-Marker include 1316 TFs, 1092 T Markers, 473 I Markers, 1600 TFMarkers and 1424 TF Pmarkers, involving 383 cell types and 95 tissue types in human. TF-Marker further provides a user-friendly interface to browse, query and visualize the detailed information about TFs and related markers. We believe TF-Marker will become a valuable resource to understand the regulation patterns of different tissues and cells.
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Bases de Datos Genéticas , Neoplasias/genética , Programas Informáticos , Factores de Transcripción/genética , Transcripción Genética , Huesos/química , Huesos/metabolismo , Encéfalo/metabolismo , Colon/química , Colon/metabolismo , Femenino , Regulación de la Expresión Génica , Marcadores Genéticos , Humanos , Internet , Hígado/química , Hígado/metabolismo , Pulmón/química , Pulmón/metabolismo , Masculino , Glándulas Mamarias Humanas/química , Glándulas Mamarias Humanas/metabolismo , Anotación de Secuencia Molecular , Neoplasias/metabolismo , Neoplasias/patología , Especificidad de Órganos , Próstata/química , Próstata/metabolismo , Factores de Transcripción/clasificación , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. METHODS: Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. RESULTS: Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. CONCLUSIONS: Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. TRIAL REGISTRATION: Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05).
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Factor Neurotrófico Derivado del Encéfalo , Depresión Posparto , Ketamina , Neurotransmisores , Serotonina , Humanos , Femenino , Ketamina/administración & dosificación , Ketamina/farmacología , Depresión Posparto/tratamiento farmacológico , Depresión Posparto/sangre , Adulto , Neurotransmisores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Serotonina/sangre , Antidepresivos/administración & dosificación , Antidepresivos/uso terapéutico , Antidepresivos/farmacología , Norepinefrina/sangre , Dopamina/sangreRESUMEN
BACKGROUND: Cervical cancer (CC) is a common malignancy of the female reproductive tract, and preoperative prediction of lymph node metastasis (LNM) is essential. This study aims to design and validate a magnetic resonance imaging (MRI) radiomics-based predictive model capable of detecting LNM in patients diagnosed with CC. METHODS: This retrospective analysis incorporated 86 and 38 CC patients into the training and testing groups, respectively. Radiomics features were extracted from MRI T2WI, T2WI-SPAIR, and axial apparent diffusion coefficient (ADC) sequences. Selected features identified in the training group were then used to construct a radiomics scoring model, with relevant LNM-related risk factors having been identified through univariate and multivariate logistic regression analyses. The resultant predictive model was then validated in the testing cohort. RESULTS: In total, 16 features were selected for the construction of a radiomics scoring model. LNM-related risk factors included worse differentiation (P < 0.001), more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P = 0.03), and a higher radiomics score from the combined MRI sequences (P = 0.01). The equation for the predictive model was as follows: -0.0493-2.1410 × differentiation level + 7.7203 × radiomics score of combined sequences + 1.6752 × FIGO stage. The respective area under the curve (AUC) values for the T2WI radiomics score, T2WI-SPAIR radiomics score, ADC radiomics score, combined sequence radiomics score, and predictive model were 0.656, 0.664, 0.658, 0.835, and 0.923 in the training cohort, while these corresponding AUC values were 0.643, 0.525, 0.513, 0.826, and 0.82 in the testing cohort. CONCLUSIONS: This MRI radiomics-based model exhibited favorable accuracy when used to predict LNM in patients with CC. Relative to the use of any individual MRI sequence-based radiomics score, this predictive model yielded superior diagnostic accuracy.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Metástasis Linfática/patología , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Radiómica , Imagen por Resonancia Magnética/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patologíaRESUMEN
OBJECTIVES: To investigate the effect of decarbromodiphenyl ether (BDE-209) exposure on the migration ability of triple-negative breast cancer (TNBC) cells and to explore the underlying mechanism. METHODS: Human TNBC MDA-MB-231 cells were divided into blank control group and BDE-209 exposure groups (treated with 0.02, 0.20, 2.00, 20.00 and 200.00 ng/mL BDE-209 in high glucose DMEM). Extracellular vehicles (EVs) secreted by MDA-MB-231 cells were isolated by differential ultracentrifugation. Transmission electron microscopy (SEM), nanoparticle tracking analysis (NTA) and Western blotting were performed to characterize the EVs. The effect of the EVs induced by BDE-209 exposure (EVs-BDE-209) on the migration and invasion of MDA-MB-231 cells was detected by wound-healing assay and Transwell test. qRT-PCR was used to measure the miR-221 level in EVs-BDE-209. The expression of MMP9 in MDA-MB-231 cells was determined by Western blotting. RESULTS: Compared with the blank control, BDE-209 exposure increased the tumor cell-derived EVs in dose-dependent manner. The MDA-MB-231 cells co-cultured with EVs released by 200.00 ng/mL BDE-209 exposure showed an 86% increase in cell migration rate, a 1.32-fold higher number of membrane-penetrating cells, a 2.71-fold higher expression level of miR-221, and a 1.62-fold higher expression level of MMP9 compared with the blank control group (all P<0.05). While transfection with anti-miR-221 antibody to decrease miR-221 level in EVs significantly reversed the increased invasion ability of the MDA-MB-231 cells treated with EVs-BDE-209. CONCLUSIONS: BDE-209 exposure may promote metastasis potential of MDA-MB-231 cells via EVs-BDE-209 transmitted miR-221.
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Movimiento Celular , Vesículas Extracelulares , Éteres Difenilos Halogenados , MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Éteres Difenilos Halogenados/farmacología , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Metaloproteinasa 9 de la Matriz/metabolismoRESUMEN
Steinberg's differential adhesion hypothesis suggests that adhesive mechanisms are important for sorting of cells and tissues during morphogenesis (Steinberg, 2007). During zebrafish vasculogenesis, endothelial cells sort into arterial and venous vessel beds but it is unknown whether this involves adhesive mechanisms. Claudins are tight junction proteins regulating the permeability of epithelial and endothelial tissue barriers. Previously, the roles of claudins during organ development have exclusively been related to their canonical functions in determining paracellular permeability. Here, we use atomic force microscopy to quantify claudin-5-dependent adhesion and find that this strongly contributes to the adhesive forces between arterial endothelial cells. Based on genetic manipulations, we reveal a non-canonical role of Claudin-5a during zebrafish vasculogenesis, which involves the regulation of adhesive forces between adjacent dorsal aortic endothelial cells. In vitro and in vivo studies demonstrate that loss of claudin-5 results in increased motility of dorsal aorta endothelial cells and in a failure of the dorsal aorta to lumenize. Our findings uncover a novel role of claudin-5 in limiting arterial endothelial cell motility, which goes beyond its traditional sealing function during embryonic development.
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Proteínas de Uniones Estrechas , Uniones Estrechas , Animales , Claudina-4 , Claudina-5/genética , Claudinas , Células Endoteliales , Pez Cebra , Proteínas de Pez CebraRESUMEN
Long noncoding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and biological functions. With the increasing study of human diseases and biological processes, information in human H3K27ac ChIP-seq, ATAC-seq and DNase-seq datasets is accumulating rapidly, resulting in an urgent need to collect and process data to identify transcriptional regulatory regions of lncRNAs. We therefore developed a comprehensive database for human regulatory information of lncRNAs (TRlnc, http://bio.licpathway.net/TRlnc), which aimed to collect available resources of transcriptional regulatory regions of lncRNAs and to annotate and illustrate their potential roles in the regulation of lncRNAs in a cell type-specific manner. The current version of TRlnc contains 8 683 028 typical enhancers/super-enhancers and 32 348 244 chromatin accessibility regions associated with 91 906 human lncRNAs. These regions are identified from over 900 human H3K27ac ChIP-seq, ATAC-seq and DNase-seq samples. Furthermore, TRlnc provides the detailed genetic and epigenetic annotation information within transcriptional regulatory regions (promoter, enhancer/super-enhancer and chromatin accessibility regions) of lncRNAs, including common SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, methylation sites, histone modifications and 3D chromatin interactions. It is anticipated that the use of TRlnc will help users to gain in-depth and useful insights into the transcriptional regulatory mechanisms of lncRNAs.
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Bases de Datos Genéticas , ARN Largo no Codificante/genética , Secuencias Reguladoras de Ácidos Nucleicos , Transcripción Genética , Inmunoprecipitación de Cromatina , Elementos de Facilitación Genéticos , Humanos , Desequilibrio de Ligamiento , Metilación , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Sitios de Carácter CuantitativoRESUMEN
OBJECTIVES: To prospectively evaluate the feasibility and biventricular assessment accuracy of a free-breathing cardiac cine imaging technique (RTCSCineMoCo) combined with highly accelerated real-time (RT) acquisition, compressed sensing (CS) reconstruction, and fully automated non-rigid respiratory motion correction. METHODS: We evaluated 80 patients scheduled for clinical cardiac MRI. Cardiac cine images of the same long-axis and short-axis stacks were acquired using three techniques: (1) SegBH: standard segmented cine with breath-hold; (2) RTCSCineMoCo; (3) RTCSCine: single-shot RT CS cine at 3.0 T. Image quality (IQ) was evaluated using a qualitative 5-point Likert scale and the European CMR registry standardized criteria. Quantitative parameters including left (LV) and right ventricular (RV) ejection fractions (EF), end-diastolic volumes (EDV), end-systolic volumes (ESV), stroke volumes (SV), and LV mass (LVM) were measured and compared. RESULTS: RTCSCineMoCo and SegBH had equivalent IQ scores (4.4 ± 0.7 vs. 4.2 ± 0.8, p = 0.066), while RTCSCine had a significantly lower IQ score than SegBH (4.0 ± 0.8 vs. 4.2 ± 0.8, p = 0.031). In a quantitative analysis, RTCSCineMoCo and SegBH yielded similar measurements for all parameters, while the majority of RTCSCine parameters were significantly different compared with SegBH, except for LVEDV. CONCLUSION: RTCSCineMoCo is a promising method for robust free-breathing cardiac cine imaging, achieving better IQ and more precise quantitative analysis results for both ventricles compared with RTCSCine. KEY POINTS: ⢠RTCSCineMoCo is a promising method for free-breathing cardiac MR cine imaging in daily practice. ⢠RTCSCineMoCo provided better IQ and more precise quantitative measurements compared with RTCSCine, by extending RT data acquisition to multiple heartbeats, performing non-rigid respiratory motion correction, and signal averaging. ⢠RTCSCineMoCo may be suitable for routine clinical use for vulnerable patients who may otherwise pose a challenge to image successfully with the conventional segmented cine technique.
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Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Cinemagnética , Humanos , Imagen por Resonancia Cinemagnética/métodos , Estudios Retrospectivos , Estudios de Factibilidad , Interpretación de Imagen Asistida por Computador/métodos , Corazón , Reproducibilidad de los ResultadosRESUMEN
Accessible chromatin is a highly informative structural feature for identifying regulatory elements, which provides a large amount of information about transcriptional activity and gene regulatory mechanisms. Human ATAC-seq datasets are accumulating rapidly, prompting an urgent need to comprehensively collect and effectively process these data. We developed a comprehensive human chromatin accessibility database (ATACdb, http://www.licpathway.net/ATACdb), with the aim of providing a large amount of publicly available resources on human chromatin accessibility data, and to annotate and illustrate potential roles in a tissue/cell type-specific manner. The current version of ATACdb documented a total of 52 078 883 regions from over 1400 ATAC-seq samples. These samples have been manually curated from over 2200 chromatin accessibility samples from NCBI GEO/SRA. To make these datasets more accessible to the research community, ATACdb provides a quality assurance process including four quality control (QC) metrics. ATACdb provides detailed (epi)genetic annotations in chromatin accessibility regions, including super-enhancers, typical enhancers, transcription factors (TFs), common single-nucleotide polymorphisms (SNPs), risk SNPs, eQTLs, LD SNPs, methylations, chromatin interactions and TADs. Especially, ATACdb provides accurate inference of TF footprints within chromatin accessibility regions. ATACdb is a powerful platform that provides the most comprehensive accessible chromatin data, QC, TF footprint and various other annotations.
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Cromatina/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Programas Informáticos , Cromatina/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Anotación de Secuencia Molecular , Análisis de Secuencia de ADN , Diseño de Software , Navegador WebRESUMEN
Long non-coding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and various biological functions. Establishing a comprehensive collection of human lncRNA sets is urgent work at present. Using reference lncRNA sets, enrichment analyses will be useful for analyzing lncRNA lists of interest submitted by users. Therefore, we developed a human lncRNA sets database, called LncSEA, which aimed to document a large number of available resources for human lncRNA sets and provide annotation and enrichment analyses for lncRNAs. LncSEA supports >40 000 lncRNA reference sets across 18 categories and 66 sub-categories, and covers over 50 000 lncRNAs. We not only collected lncRNA sets based on downstream regulatory data sources, but also identified a large number of lncRNA sets regulated by upstream transcription factors (TFs) and DNA regulatory elements by integrating TF ChIP-seq, DNase-seq, ATAC-seq and H3K27ac ChIP-seq data. Importantly, LncSEA provides annotation and enrichment analyses of lncRNA sets associated with upstream regulators and downstream targets. In summary, LncSEA is a powerful platform that provides a variety of types of lncRNA sets for users, and supports lncRNA annotations and enrichment analyses. The LncSEA database is freely accessible at http://bio.liclab.net/LncSEA/index.php.
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Biología Computacional/métodos , Bases de Datos Genéticas , Regulación de la Expresión Génica , ARN Largo no Codificante/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Factores de Transcripción/genética , Minería de Datos/métodos , Humanos , Internet , Anotación de Secuencia Molecular/métodos , Análisis de Secuencia de ARN/métodos , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND: Post-harvest quality assurance is a crucial link between grain production and end users. It is essential to ensure that grain does not deteriorate due to heating during storage. To visualize the temperature distribution of a grain pile, the present study proposed a three-dimensional (3D) temperature field visualization method based on an adaptive neighborhood clustering algorithm (ANCA). The ANCA-based visualization method contains four calculation modules. First, discrete grain temperature data, obtained by sensors, are collected and interpolated using back propagation (BP) neural networks to model the temperature field. Then a new adaptive neighborhood clustering algorithm is applied to divide interpolation data into different categories by combining spatial characteristics and spatiotemporal information. Next, the Quickhull algorithm is used to compute the boundary points of each cluster. Finally, the polyhedrons determined by boundary points are rendered into different colors and are constructed in a 3D temperature model of the grain pile. RESULTS: The experimental results show that ANCA is much better than the DBSCAN and MeanShift algorithms on compactness (around 95.7% of tested cases) and separation (approximately 91.3% of tested cases). Moreover, the ANCA-based visualization method for grain pile temperatures has a shorter rendering time and better visual effects. CONCLUSION: This research provides an efficient 3D visualization method that allows managers of grain depots to obtain temperature field information for bulk grain visually in real time to help them protect grain quality during storage. © 2023 Society of Chemical Industry.
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Anticuerpos Anticitoplasma de Neutrófilos , Imagenología Tridimensional , Imagenología Tridimensional/métodos , Temperatura , Algoritmos , Análisis por Conglomerados , TecnologíaRESUMEN
OBJECTIVES: To systematically evaluate the value of the platelet-to-lymphocyte ratio (PLR) in predicting coronary artery lesions (CAL) in Chinese children with Kawasaki Disease (KD). METHODS: A comprehensive search was conducted in databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database from inception to December 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale, and a Meta analysis was performed using Stata 15.1. RESULTS: A total of ten published reports, involving 3 664 Chinese children with KD, were included in this Meta analysis, of whom 1 328 developed CAL. The Meta analysis revealed a sensitivity of 0.78 (95%CI: 0.71-0.83), specificity of 0.71 (95%CI: 0.61-0.80), overall diagnostic odds ratio of 8.69 (95%CI: 5.02-15.06), and an area under the curve of the summary receiver operating characteristic of 0.82 (95%CI: 0.78-0.85) for PLR in predicting CAL in the children with KD. The sensitivity, specificity, and area under the curve of summary receiver operating characteristic were lower for PLR alone compared to PLR in combination with other indicators. Sensitivity analysis demonstrated the stability of the Meta analysis results with no significant changes upon excluding individual studies. However, a significant publication bias was observed (P<0.001). CONCLUSIONS: PLR demonstrates certain predictive value for CAL in Chinese children with KD.
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Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Niño , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/patología , Vasos Coronarios/patología , Linfocitos , Biomarcadores , China , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patologíaRESUMEN
Controlling the conformation of medium-sized rings is challenging because of their flexibility and ring strain effects. Herein, we report non-Curtin-Hammett conditions for the precise control of the conformation of cyclodecenones to effect the first cis-selective transannular Prins cyclization, which enabled concise syntheses of the 5(10â1)abeo-steroids bufospirostenin A and ophiopogonol A in only seven steps from inexpensive starting materials. Computational results indicated that the key cyclization was kinetically controlled and proceeded via either a Prins pathway or a carbonyl-ene pathway, depending on the reaction conditions. Moreover, conformational isomerization played a critical role in determining the stereochemistry of the products.
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Ciclización , Bufanólidos , Conformación Molecular , EstereoisomerismoRESUMEN
OBJECTIVES: To explore the impact of deep learning reconstruction (DLR) on image quality and machine learning-based coronary CT angiography (CTA)-derived fractional flow reserve (CT-FFRML) values. METHODS: Thirty-three consecutive patients with known or suspected coronary artery disease who underwent coronary CTA and subsequent invasive coronary angiography were enrolled. DLR was compared with filtered back projection (FBP), statistical-based iterative reconstruction (SBIR), model-based iterative reconstruction (MBIR) Cardiac, and MBIR Cardiac sharp for objective image qualities of coronary CTA. Invasive fractional flow reserve (FFR) and quantitative flow ratio (QFR) were used as the reference standards. The diagnostic performances of different reconstruction approach-based CT-FFRML were calculated. RESULTS: A total of 182 lesions in 33 patients were enrolled for analysis. The image quality of DLR was superior to the others. There were no significant differences in the CT-FFRML values among these five approaches (all p > 0.05). Of the 182 lesions, 17 had invasive FFR results, and 70 had QFR results. Using FFR as a reference, MBIR Cardiac, MBIR Cardiac sharp, and DLR achieved equal diagnostic performance, slightly higher than the other reconstruction approaches (MBIR Cardiac, MBIR Cardiac sharp, and DLR: AUC = 0.82, FBP and AIDR: AUC = 0.78, all p > 0.05). Using QFR as a reference, the AUCs of FBP, SBIR, MBIR Cardiac, MBIR Cardiac sharp, and DLR were 0.83, 0.81, 0.86, 0.84, and 0.83, respectively (all p > 0.05). CONCLUSIONS: Our study showed that the DLR algorithm improved image quality, but there were no significant differences in the CT-FFRML values and diagnostic performance among different reconstruction approaches. KEY POINTS: ⢠Deep learning-based image reconstruction (DLR) improves the image quality of coronary CTA. ⢠CT-FFRML values and diagnostic performance of DLR revealed no significant differences compared to other reconstruction approaches.
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Aprendizaje Profundo , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria/métodos , Angiografía por Tomografía Computarizada/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Transcription factors (TFs) and their target genes have important functions in human diseases and biological processes. Gene expression profile analysis before and after knockdown or knockout is one of the most important strategies for obtaining target genes of TFs and exploring TF functions. Human gene expression profile datasets with TF knockdown and knockout are accumulating rapidly. Based on the urgent need to comprehensively and effectively collect and process these data, we developed KnockTF (http://www.licpathway.net/KnockTF/index.html), a comprehensive human gene expression profile database of TF knockdown and knockout. KnockTF provides a number of resources for human gene expression profile datasets associated with TF knockdown and knockout and annotates TFs and their target genes in a tissue/cell type-specific manner. The current version of KnockTF has 570 manually curated RNA-seq and microarray datasets associated with 308 TFs disrupted by different knockdown and knockout techniques and across multiple tissue/cell types. KnockTF collects upstream pathway information of TFs and functional annotation results of downstream target genes. It provides details about TFs binding to promoters, super-enhancers and typical enhancers of target genes. KnockTF constructs a TF-differentially expressed gene network and performs network analyses for genes of interest. KnockTF will help elucidate TF-related functions and potential biological effects.
Asunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Técnicas de Silenciamiento del Gen , Programas Informáticos , Factores de Transcripción/genética , Humanos , Anotación de Secuencia Molecular , Factores de Transcripción/metabolismo , Interfaz Usuario-Computador , Navegador WebRESUMEN
Enhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Although some enhancer databases have been published, most only focus on enhancers identified by high-throughput experimental techniques. Therefore, it is highly desirable to construct a comprehensive resource of manually curated enhancers and their related information based on low-throughput experimental evidences. Here, we established a comprehensive manually-curated enhancer database for human and mouse, which provides a resource for experimentally supported enhancers, and to annotate the detailed information of enhancers. The current release of ENdb documents 737 experimentally validated enhancers and their related information, including 384 target genes, 263 TFs, 110 diseases and 153 functions in human and mouse. Moreover, the enhancer-related information was supported by experimental evidences, such as RNAi, in vitro knockdown, western blotting, qRT-PCR, luciferase reporter assay, chromatin conformation capture (3C) and chromosome conformation capture-on-chip (4C) assays. ENdb provides a user-friendly interface to query, browse and visualize the detailed information of enhancers. The database is available at http://www.licpathway.net/ENdb.