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1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3016-3023, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467691

RESUMO

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.


Assuntos
Medicamentos de Ervas Chinesas , Distúrbios do Início e da Manutenção do Sono , Animais , Bases de Dados Genéticas , Medicamentos de Ervas Chinesas/farmacologia , Ontologia Genética , Humanos , Medicina Tradicional Chinesa , Camundongos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/genética
2.
Sci Rep ; 11(1): 17473, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471195

RESUMO

As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Regulação para Cima , COVID-19/imunologia , Linhagem Celular , Bases de Dados Genéticas , Feminino , Humanos , Imunidade Inata , Masculino , Modelos Biológicos , Modelos Teóricos , Caracteres Sexuais
3.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445498

RESUMO

Aberrant alternative splicing (AS) is increasingly linked to cancer; however, how AS contributes to cancer development still remains largely unknown. AS events (ASEs) are largely regulated by RNA-binding proteins (RBPs) whose ability can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we used a computational framework to investigate the roles of transcription factors (TFs) on regulating RBP-AS interactions. A total of 6519 TF-RBP-AS triplets were identified, including 290 TFs, 175 RBPs, and 16 ASEs from TCGA-KIRC RNA sequencing data. TF function categories were defined according to correlation changes between RBP expression and their targeted ASEs. The results suggested that most TFs affected multiple targets, and six different classes of TF-mediated transcriptional dysregulations were identified. Then, regulatory networks were constructed for TF-RBP-AS triplets. Further pathway-enrichment analysis showed that these TFs and RBPs involved in triplets were enriched in a variety of pathways that were associated with cancer development and progression. Survival analysis showed that some triplets were highly associated with survival rates. These findings demonstrated that the integration of TFs into alternative splicing regulatory networks can help us in understanding the roles of alternative splicing in cancer.


Assuntos
Processamento Alternativo , Biologia Computacional/métodos , Neoplasias Renais/genética , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Renais/metabolismo , Prognóstico , Mapas de Interação de Proteínas , Análise de Sequência de RNA , Análise de Sobrevida
4.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445502

RESUMO

Trace amine-associated receptors (TAAR) recognize organic compounds, including primary, secondary, and tertiary amines. The TAAR5 receptor is known to be involved in the olfactory sensing of innate socially relevant odors encoded by volatile amines. However, emerging data point to the involvement of TAAR5 in brain functions, particularly in the emotional behaviors mediated by the limbic system which suggests its potential contribution to the pathogenesis of neuropsychiatric diseases. TAAR5 expression was explored in datasets available in the Gene Expression Omnibus, Allen Brain Atlas, and Human Protein Atlas databases. Transcriptomic data demonstrate ubiquitous low TAAR5 expression in the cortical and limbic brain areas, the amygdala and the hippocampus, the nucleus accumbens, the thalamus, the hypothalamus, the basal ganglia, the cerebellum, the substantia nigra, and the white matter. Altered TAAR5 expression is identified in Down syndrome, major depressive disorder, or HIV-associated encephalitis. Taken together, these data indicate that TAAR5 in humans is expressed not only in the olfactory system but also in certain brain structures, including the limbic regions receiving olfactory input and involved in critical brain functions. Thus, TAAR5 can potentially be involved in the pathogenesis of brain disorders and represents a valuable novel target for neuropsychopharmacology.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/genética , Síndrome de Down/genética , Regulação para Baixo , Encefalite Viral/genética , Infecções por HIV/complicações , Receptores Acoplados a Proteínas G/genética , Bases de Dados Genéticas , Encefalite Viral/etiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Infecções por HIV/genética , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Sequência de RNA , Distribuição Tecidual
5.
Int J Mol Sci ; 22(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34445220

RESUMO

Recently, the quest for the mythical fountain of youth has produced extensive research programs that aim to extend the healthy lifespan of humans. Despite advances in our understanding of the aging process, the surprisingly extended lifespan and cancer resistance of some animal species remain unexplained. The p53 protein plays a crucial role in tumor suppression, tissue homeostasis, and aging. Long-lived, cancer-free African elephants have 20 copies of the TP53 gene, including 19 retrogenes (38 alleles), which are partially active, whereas humans possess only one copy of TP53 and have an estimated cancer mortality rate of 11-25%. The mechanism through which p53 contributes to the resolution of the Peto's paradox in Animalia remains vague. Thus, in this work, we took advantage of the available datasets and inspected the p53 amino acid sequence of phylogenetically related organisms that show variations in their lifespans. We discovered new correlations between specific amino acid deviations in p53 and the lifespans across different animal species. We found that species with extended lifespans have certain characteristic amino acid substitutions in the p53 DNA-binding domain that alter its function, as depicted from the Phenotypic Annotation of p53 Mutations, using the PROVEAN tool or SWISS-MODEL workflow. In addition, the loop 2 region of the human p53 DNA-binding domain was identified as the longest region that was associated with longevity. The 3D model revealed variations in the loop 2 structure in long-lived species when compared with human p53. Our findings show a direct association between specific amino acid residues in p53 protein, changes in p53 functionality, and the extended animal lifespan, and further highlight the importance of p53 protein in aging.


Assuntos
Bases de Dados Genéticas , Dosagem de Genes , Longevidade , Modelos Moleculares , Animais , Domínios Proteicos , Estrutura Secundária de Proteína , Especificidade da Espécie , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445418

RESUMO

Central pattern generators produce rhythmic behaviors independently of sensory input; however, their outputs can be modulated by neuropeptides, thereby allowing for functional flexibility. We investigated the effects of C-type allatostatins (AST-C) on the cardiac ganglion (CG), which is the central pattern generator that controls the heart of the American lobster, Homarus americanus, to identify the biological mechanism underlying the significant variability in individual responses to AST-C. We proposed that the presence of multiple receptors, and thus differential receptor distribution, was at least partly responsible for this observed variability. Using transcriptome mining and PCR-based cloning, we identified four AST-C receptors (ASTCRs) in the CG; we then characterized their cellular localization, binding potential, and functional activation. Only two of the four receptors, ASTCR1 and ASTCR2, were fully functional GPCRs that targeted to the cell surface and were activated by AST-C peptides in our insect cell expression system. All four, however, were amplified from CG cDNAs. Following the confirmation of ASTCR expression, we used physiological and bioinformatic techniques to correlate receptor expression with cardiac responses to AST-C across individuals. Expression of ASTCR1 in the CG showed a negative correlation with increasing contraction amplitude in response to AST-C perfusion through the lobster heart, suggesting that the differential expression of ASTCRs within the CG is partly responsible for the specific physiological response to AST-C exhibited by a given individual lobster.


Assuntos
Perfilação da Expressão Gênica/métodos , Nephropidae/genética , Neuropeptídeos/farmacologia , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Sistema Cardiovascular/metabolismo , Membrana Celular/metabolismo , Clonagem Molecular , Mineração de Dados , Bases de Dados Genéticas , Regulação da Expressão Gênica/efeitos dos fármacos , Miocárdio/metabolismo , Nephropidae/efeitos dos fármacos , Nephropidae/metabolismo , Análise de Sequência de RNA , Células Sf9 , Distribuição Tecidual
7.
PLoS One ; 16(8): e0256141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34407143

RESUMO

SARS-CoV-2 requires serine protease, transmembrane serine protease 2 (TMPRSS2), and cysteine proteases, cathepsins B, L (CTSB/L) for entry into host cells. These host proteases activate the spike protein and enable SARS-CoV-2 entry. We herein performed genomic-guided gene set enrichment analysis (GSEA) to identify upstream regulatory elements altering the expression of TMPRSS2 and CTSB/L. Further, medicinal compounds were identified based on their effects on gene expression signatures of the modulators of TMPRSS2 and CTSB/L genes. Using this strategy, estradiol and retinoic acid have been identified as putative SARS-CoV-2 alleviation agents. Next, we analyzed drug-gene and gene-gene interaction networks using 809 human targets of SARS-CoV-2 proteins. The network results indicate that estradiol interacts with 370 (45%) and retinoic acid interacts with 251 (31%) human proteins. Interestingly, a combination of estradiol and retinoic acid interacts with 461 (56%) of human proteins, indicating the therapeutic benefits of drug combination therapy. Finally, molecular docking analysis suggests that both the drugs bind to TMPRSS2 and CTSL with the nanomolar to low micromolar affinity. The results suggest that these drugs can simultaneously target both the entry pathways of SARS-CoV-2 and thus can be considered as a potential treatment option for COVID-19.


Assuntos
Catepsina B/genética , Catepsina L/genética , Estradiol/farmacologia , Genômica/métodos , SARS-CoV-2/fisiologia , Serina Endopeptidases/genética , Tretinoína/farmacologia , Catepsina B/química , Catepsina L/química , Bases de Dados Genéticas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Mapas de Interação de Proteínas/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Serina Endopeptidases/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos
8.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34369278

RESUMO

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Carcinoma Hepatocelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Receptores Virais/genética , alfa-Fetoproteínas/genética , Fatores Etários , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Área Sob a Curva , COVID-19/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Fatores de Proteção , Mapeamento de Interação de Proteínas , Curva ROC , Receptores Virais/metabolismo , SARS-CoV-2/patogenicidade , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
9.
Adv Protein Chem Struct Biol ; 127: 315-342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34340772

RESUMO

Lung Emphysema is an abnormal enlargement of the air sacs followed by the destruction of alveolar walls without any prominent fibrosis. This study primarily identifies the differentially expressed genes (DEGs), interactions between them, and their significant involvement in the activated signaling cascades. The dataset with ID GSE1122 (five normal lung tissue samples, five of usual emphysema, and five of alpha-1 antitrypsin deficiency-related emphysema) from the gene expression omnibus (GEO) was analyzed using the GEO2R tool. The physical association between the DEGs were mapped using the STRING tool and was visualized in the Cytoscape software. The enriched functional processes were identified with the ClueGO plugin's help from Cytoscape. Further integrative functional annotation was performed by implying the GeneGo Metacore™ to distinguish the enriched pathway maps, process networks, and GO processes. The results from this analysis revealed the critical signaling cascades that have been either activated or inhibited due to identified DEGs. We found the activated pathways such as immune response IL-1 signaling pathway, positive regulation of smooth muscle migration, BMP signaling pathway, positive regulation of leukocyte migration, NIK/NF-kappB signaling, and cytochrome-c oxidase activity. Finally, we mapped four crucial genes (CCL5, ALK, TAC1, CD74, and HLA-DOA) by comparing the functional annotations that could be significantly influential in emphysema molecular pathogenesis. Our study provides insights into the pathogenesis of emphysema and helps in developing potential drug targets against emphysema.


Assuntos
Bases de Dados Genéticas , Enfisema Pulmonar , Transdução de Sinais/genética , Biologia de Sistemas , Deficiência de alfa 1-Antitripsina , Humanos , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Deficiência de alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/metabolismo
10.
Methods Mol Biol ; 2351: 67-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382184

RESUMO

The Cap Analysis of Gene Expression (CAGE) is a powerful method to identify Transcription Start Sites (TSSs) of capped RNAs while simultaneously measuring transcripts expression level. CAGE allows mapping at single nucleotide resolution at all active promoters and enhancers. Large CAGE datasets have been produced over the years from individual laboratories and consortia, including the Encyclopedia of DNA Elements (ENCODE) and Functional Annotation of the Mammalian Genome (FANTOM) consortia. These datasets constitute open resource for TSS annotations and gene expression analysis. Here, we provide an experimental protocol for the most recent CAGE method called Low Quantity (LQ) single strand (ss) CAGE "LQ-ssCAGE", which enables cost-effective profiling of low quantity RNA samples. LQ-ssCAGE is especially useful for samples derived from cells cultured in small volumes, cellular compartments such as nuclear RNAs or for samples from developmental stages. We demonstrate the reproducibility and effectiveness of the method by constructing 240 LQ-ssCAGE libraries from 50 ng of THP-1 cell extracted RNAs and discover lowly expressed novel enhancer and promoter-derived lncRNAs.


Assuntos
Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Regiões Promotoras Genéticas , Capuzes de RNA , Sítio de Iniciação de Transcrição , Bases de Dados Genéticas , Regulação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Anotação de Sequência Molecular , Sequências Reguladoras de Ácido Nucleico , Reprodutibilidade dos Testes , Fluxo de Trabalho
11.
Methods Mol Biol ; 2351: 201-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34382191

RESUMO

Regulation of gene expression is a key feature for higher eukaryotes and how chromatin topology relates to gene activation is an intense area of research. Enhancer-promoter interactions are believed to mediate activation of target genes. Bidirectional transcription represents one hallmark of active enhancers that can be measured using transcriptome technologies such as Cap analysis of gene expression (CAGE). Recently, we have developed RNA and DNA interacting complexes ligated and sequenced (RADICL-Seq) a novel methodology to map genome-wide RNA-chromatin interactions in intact nuclei. Here, we describe how CAGE and RADICL-Seq data can be used to characterize enhancer elements and identify their target genes.


Assuntos
Biologia Computacional/métodos , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Capuzes de RNA , Algoritmos , Cromatina/genética , Bases de Dados Genéticas , Sequenciamento de Nucleotídeos em Larga Escala , Sítio de Iniciação de Transcrição , Transcrição Genética , Ativação Transcricional , Transcriptoma
12.
Medicine (Baltimore) ; 100(32): e26474, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397869

RESUMO

ABSTRACT: This study is to identify potential biomarkers and therapeutic targets for lung adenocarcinoma (LUAD).GSE6044 and GSE118370 raw data from the Gene Expression Omnibus database were normalized with Robust Multichip Average. After merging these two datasets, the combat function of sva packages was used to eliminate batch effects. Then, limma packages were used to filtrate differentially expressed genes. We constructed protein-protein interaction relationships using STRING database and hub genes were identified based on connectivity degrees. The cBioportal database was used to explore the alterations of the hub genes. The promoter methylation of cyclin dependent kinase 1 (CDK1) and polo-like Kinase 1 (PLK1) and their association with tumor immune infiltration in patients with LUAD were investigated using DiseaseMeth version 2.0 and TIMER databases. The Cancer Genome Atlas-LUAD dataset was used to perform gene set enrichment analysis.We identified 10 hub genes, which were upregulated in LUAD, among which 8 were successfully verified in the Cancer Genome Atlas and Oncomine databases. Kaplan-Meier analysis indicated that the expressions of CDK1 and PLK1 in LUAD patients were associated with overall survival and disease-free survival. The methylation levels in the promoter regions of these 2 genes in LUAD patients were lower than those in normal lung tissues. Their expressions in LUAD were associated with tumor stages and relative abundance of tumor infiltrating immune cells, such as B cells, CD4+ T cells, and macrophages. Moreover, cell cycle, DNA replication, homologous recombination, mismatch repair, P53 signaling pathway, and small cell lung cancer signaling were significantly enriched in CDK1 and PLK1 high expression phenotype.CDK1 and PLK1 may be used as potential biomarkers and therapeutic targets for LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Proteína Quinase CDC2/genética , Proteínas de Ciclo Celular/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Proteína Quinase CDC2/biossíntese , Proteínas de Ciclo Celular/biossíntese , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Prognóstico , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , RNA Neoplásico/genética , Transdução de Sinais
13.
Arch Virol ; 166(10): 2937-2942, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34347169

RESUMO

The genus Gyrovirus was assigned to the family Anelloviridae in 2017 with only one recognized species, Chicken anemia virus. Over the last decade, many diverse viruses related to chicken anemia virus have been identified but not classified. Here, we provide a framework for the classification of new species in the genus Gyrovirus and communicate the establishment of nine new species. We adopted the 'Genus + freeform epithet' binomial system for the naming of these species.


Assuntos
Gyrovirus/classificação , Terminologia como Assunto , Anelloviridae/classificação , Anelloviridae/genética , Animais , Proteínas do Capsídeo/genética , Vírus da Anemia da Galinha/classificação , Vírus da Anemia da Galinha/genética , DNA Viral/genética , Bases de Dados Genéticas , Genoma Viral/genética , Gyrovirus/genética , Humanos , Filogenia , Análise de Sequência de DNA
14.
Arch Virol ; 166(10): 2943-2953, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34383165

RESUMO

Anelloviruses are small negative-sense single-stranded DNA viruses with genomes ranging in size from 1.6 to 3.9 kb. The family Anelloviridae comprised 14 genera before the present changes. However, in the last five years, a large number of diverse anelloviruses have been identified in various organisms. Here, we undertake a global analysis of mammalian anelloviruses whose full genome sequences have been determined and have an intact open reading frame 1 (ORF1). We established new criteria for the classification of anelloviruses, and, based on our analyses, we establish new genera and species to accommodate the unclassified anelloviruses. We also note that based on the updated species demarcation criteria, some previously assigned species (n = 10) merge with other species. Given the rate at which virus sequence data are accumulating, and with the identification of diverse anelloviruses, we acknowledge that the taxonomy will have to be dynamic and continuously evolve to accommodate new members.


Assuntos
Anelloviridae/classificação , Mamíferos/virologia , Anelloviridae/genética , Animais , Sequência de Bases , DNA Viral/genética , Bases de Dados Genéticas , Genoma Viral/genética , Fases de Leitura Aberta/genética , Filogenia , Terminologia como Assunto
15.
Cell Rep ; 36(7): 109527, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34348131

RESUMO

COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. To expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients, including matched analysis of the whole-blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate herein the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide.


Assuntos
COVID-19/genética , COVID-19/metabolismo , Bases de Dados Genéticas , Metaboloma , Proteoma , Transcriptoma , Acesso à Informação , Adulto , COVID-19/imunologia , Estudos de Casos e Controles , Mineração de Dados , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Proteômica , Adulto Jovem
16.
BMC Plant Biol ; 21(1): 371, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384382

RESUMO

BACKGROUND: The Orchid family is the largest families of the monocotyledons and an economically important ornamental plant worldwide. Given the pivotal role of this plant to humans, botanical researchers and breeding communities should have access to valuable genomic and transcriptomic information of this plant. Previously, we established OrchidBase, which contains expressed sequence tags (ESTs) from different tissues and developmental stages of Phalaenopsis as well as biotic and abiotic stress-treated Phalaenopsis. The database includes floral transcriptomic sequences from 10 orchid species across all the five subfamilies of Orchidaceae. DESCRIPTION: Recently, the whole-genome sequences of Apostasia shenzhenica, Dendrobium catenatum, and Phalaenopsis equestris were de novo assembled and analyzed. These datasets were used to develop OrchidBase 4.0, including genomic and transcriptomic data for these three orchid species. OrchidBase 4.0 offers information for gene annotation, gene expression with fragments per kilobase of transcript per millions mapped reads (FPKM), KEGG pathways and BLAST search. In addition, assembled genome sequences and location of genes and miRNAs could be visualized by the genome browser. The online resources in OrchidBase 4.0 can be accessed by browsing or using BLAST. Users can also download the assembled scaffold sequences and the predicted gene and protein sequences of these three orchid species. CONCLUSIONS: OrchidBase 4.0 is the first database that contain the whole-genome sequences and annotations of multiple orchid species. OrchidBase 4.0 is available at http://orchidbase.itps.ncku.edu.tw/.


Assuntos
Bases de Dados Genéticas , Orchidaceae/genética , Genoma de Planta
17.
Nat Commun ; 12(1): 4764, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362913

RESUMO

As global demand for digital storage capacity grows, storage technologies based on synthetic DNA have emerged as a dense and durable alternative to traditional media. Existing approaches leverage robust error correcting codes and precise molecular mechanisms to reliably retrieve specific files from large databases. Typically, files are retrieved using a pre-specified key, analogous to a filename. However, these approaches lack the ability to perform more complex computations over the stored data, such as similarity search: e.g., finding images that look similar to an image of interest without prior knowledge of their file names. Here we demonstrate a technique for executing similarity search over a DNA-based database of 1.6 million images. Queries are implemented as hybridization probes, and a key step in our approach was to learn an image-to-sequence encoding ensuring that queries preferentially bind to targets representing visually similar images. Experimental results show that our molecular implementation performs comparably to state-of-the-art in silico algorithms for similarity search.


Assuntos
Biologia Computacional/métodos , DNA/química , Bases de Dados Genéticas , Armazenamento e Recuperação da Informação , Algoritmos , Sequência de Bases , Simulação por Computador , DNA/genética , Sondas de DNA , Bases de Dados Factuais , Redes Neurais de Computação
18.
World J Surg Oncol ; 19(1): 248, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419055

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. METHODS: A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein-protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro. RESULTS: A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro. CONCLUSIONS: HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.


Assuntos
Neoplasias Colorretais , Insulina , Proteínas , Receptores Nicotínicos , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Receptores Acoplados a Proteínas G
19.
Medicine (Baltimore) ; 100(31): e26439, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397793

RESUMO

ABSTRACT: This study aimed to investigate the expression and clinical significance of aurora B kinase (AURKB) gene in lung adenocarcinoma (LUAD) by collecting relevant data in Oncomine database.Firstly, mRNA expression level of AURKB in LUAD was systematically analyzed using the ONCOMINE and the cancer genome atlas databases. Then, the association between AURKB expression and clinical parameters was investigated by UALCAN. The Kaplan-Meier Plotter was used to assess the prognostic significance of AURKB.Pooled analysis showed that AURKB was frequently up-regulated expression in LUAD. In addition, immunohistochemistry showed that AURKB was highly expressed in lung adenocarcinoma tissues, while it was weakly expressed in normal tissues. Subsequently, AURKB expression was identified to be negatively associated with Overall survival (P < 1e-16), post-progression survival (P = .017), first progression (P = 9.8e-09).This study confirms that increased expression of AURKB in LUAD is associated with poor prognosis, suggesting that AURKB might be used as a promising prognostic biomarker and novel therapeutic target for LUAD.


Assuntos
Adenocarcinoma/genética , Aurora Quinase B/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Idoso , Aurora Quinase B/metabolismo , Biologia Computacional , Mineração de Dados , Bases de Dados Genéticas , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Regulação para Cima
20.
Medicine (Baltimore) ; 100(31): e26623, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397798

RESUMO

BACKGROUND: Cyclin F (CCNF) dysfunction has been implicated in various forms of cancer, offering a new avenue for understanding the pathogenic mechanisms underlying hepatocellular carcinoma (HCC). We aimed to evaluate the role of CCNF in HCC using publicly available data from The Cancer Genome Atlas (TCGA). METHOD: We used TCGA data and Gene Expression Omnibus (GEO) data to analyze the differential expression of CCNF between tumor and adjacent tissues and the relationship between CCNF and clinical characteristics. We compared prognosis of patients with HCC with high and low CCNF expression and constructed receiver operating characteristic (ROC) curves. In addition, we also explored the types of gene mutations in relevant groups and conducted Gene Set Enrichment Analysis (GSEA). RESULTS: The expression of CCNF in liver cancer tissues was significantly increased compared with that in adjacent tissues, and patients with high CCNF expression had a worse prognosis than those with low CCNF expression. Patients with high CCNF expression also had more somatic mutations. High expression of CCNF hampers the prognosis independently. The GSEA showed that the "http://www.gsea-msigdb.org/gsea/msigdb/cards/BIOCARTA_WNT_PATHWAY" Wnt pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/BIOCARTA_P53_PATHWAY" P53 pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/HALLMARK_PI3K_AKT_MTOR_SIGNALING" PI3K/Akt/mTOR pathway, "http://www.gsea-msigdb.org/gsea/msigdb/cards/HALLMARK_NOTCH_SIGNALING" Notch pathway were enriched in patients with the high CCNF expression phenotype. CONCLUSION: High CCNF expression can be seen as an independent risk factor for poor survival in HCC. Its expression may serve as a target for the diagnosis and treatment of liver cancer.


Assuntos
Carcinoma Hepatocelular/genética , Ciclinas/genética , Neoplasias Hepáticas/genética , Transdução de Sinais/genética , Carcinoma Hepatocelular/metabolismo , Ciclinas/metabolismo , Bases de Dados Genéticas , Feminino , Expressão Gênica , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Fosfatidilinositol 3-Quinase/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Curva ROC , Receptores Notch/metabolismo , Taxa de Sobrevida , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização Wnt/genética
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