Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.208
Filtrar
1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 795-797, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365628

RESUMO

OBJECTIVE: To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes. METHODS: 328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities. RESULTS: The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05). CONCLUSION: Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.


Assuntos
Aneuploidia , Variações do Número de Cópias de DNA , Aberrações Cromossômicas , Feminino , Feto , Humanos , Análise em Microsséries , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
2.
BMC Res Notes ; 14(1): 340, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461994

RESUMO

OBJECTIVE: The incidence of ductal carcinoma in situ (DCIS) is increasing due to more widespread mammographic screening. DCIS, the earliest form of breast cancer, is non-invasive at the time of detection. If DCIS tissues are left undetected or untreated, it can spread to the surrounding breast tissue. Thus, surgical resection is the standard treatment. Understanding the mechanism underlying the non-invasive property of DCIS could lead to more appropriate medical treatments, including nonsurgical options. DATA DESCRIPTION: We conducted a microarray-based genome-wide transcriptome analysis using DCIS specimens obtained by puncture from surgical specimens immediately after surgery.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mamografia , Análise em Microsséries , Punções
3.
Anal Chem ; 93(34): 11887-11895, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34398607

RESUMO

Herein, a novel liquid crystal microarray (LCM) film with optical regulation ability is first constructed by combining liquid crystals (LC) and the highly ordered microporous structure of inverse opal photonic crystals (IOPhCs). The LCM films are fabricated by infiltrating LC molecules into the LC polymer with the structure of IOPhCs, and their properties are very different from those without the LC. Interestingly, the optical property of LCM films can be controlled by changing the orientation of LC molecules, which varies with the interfacial force. In combination with polarization images, spectral reflection peak, circular dichroism spectra, potential difference, and fluorescence images of LCM films, the mechanism of this change is investigated. It is found that the exposed basic group of single-stranded DNA is the key to the change of the optical property of LC microarrays. Meanwhile, the optical signals of LC microarrays based on the PhCs provide a novel LC signal mode for an LC sensing system (microspectral signal mode), and it can be recorded by a fiber-optic spectrometer, which is a great improvement on LC sensing signals. Therefore, the LC microarray sensing signal can be used for accurate analysis of targets by the change of the reflection peak intensity of PhCs. When the LC molecules are induced by different aptamers, the LC microarray sensing interface can be further used for the determination of different targets, such as cocaine and Hg2+. The research on LCM films is of significant value for the development of LC sensing technology and also shows great application prospects in biochemical sensing fields.


Assuntos
Cristais Líquidos , Análise em Microsséries , Óptica e Fotônica , Fótons , Refratometria
4.
Medicine (Baltimore) ; 100(30): e26582, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397688

RESUMO

BACKGROUND: Tuberculosis (TB) is a global health problem that brings us numerous difficulties. Diverse genetic factors play a significant role in the progress of TB disease. However, still no key genes for TB susceptibility have been reported. This study aimed to identify the key genes of TB through comprehensive bioinformatics analysis. METHODS: The series microarray datasets from the gene expression omnibus (GEO) database were analyzed. We used the online tool GEO2R to filtrate differentially expressed genes (DEGs) between TB and health control. Database for annotation can complete gene ontology function analysis as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein-protein interaction (PPI) networks of DEGs were established by STRING online tool and visualized by Cytoscape software. Molecular Complex Detection can complete the analysis of modules in the PPI networks. Finally, the significant hub genes were confirmed by plug-in Genemania of Cytoscape, and verified by the verification cohort and protein test. RESULTS: There are a total of 143 genes were confirmed as DEGs, containing 48 up-regulated genes and 50 down-regulated genes. The gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis show that upregulated DEGs were associated with cancer and phylogenetic, whereas downregulated DEGs mainly concentrate on inflammatory immunity. PPI networks show that signal transducer and activator of transcription 1 (STAT1), guanylate binding protein 5 (GBP5), 2'-5'-oligoadenylate synthetase 1 (OAS1), catenin beta 1 (CTNNB1), and guanylate binding protein 1 (GBP1) were identified as significantly different hub genes. CONCLUSION: We conclude that these genes, including TAT1, GBP5, OAS1, CTNNB1, GBP1 are a candidate as potential core genes in TB and treatment of TB in the future.


Assuntos
Tuberculose/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Análise em Microsséries
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 659-662, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247372

RESUMO

OBJECTIVE: To analyze the prenatal diagnosis, parental verification and pregnancy outcome of 6 fetuses with 22q11.2 microdeletion syndrome. METHODS: Copy number variation sequencing (CNV-seq)and chromosomal microarray analysis (CMA) were carried out for the fetuses. RESULTS: The fetuses were found to harbor 2.54-3.2 Mb microdeletions of the 22q11.2 region, among which one was maternally inherited and one was paternally inherited. Two parents opted to continue with the pregnancy, and 4 chose induced labor. One fetus was found to have tetralogy of Fallot, while two carrier parents and one fetus appeared to have normal phenotype. CONCLUSION: 22q11.2 microdeletions identified upon prenatal diagnosis should be treated carefully, with ultrasonic scan and parental verification taken into account.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Feminino , Feto , Humanos , Análise em Microsséries , Gravidez , Resultado da Gravidez , Ultrassonografia Pré-Natal
6.
Am J Hum Genet ; 108(8): 1409-1422, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237280

RESUMO

Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics. Drawbacks of these tests are a very low resolution (karyotyping) and the inability to detect balanced SVs or indicate the genomic localization and orientation of duplicated segments or insertions (copy number variant [CNV] microarrays). Here, we investigated the ability of optical genome mapping (OGM) to detect known constitutional chromosomal aberrations. Ultra-high-molecular-weight DNA was isolated from 85 blood or cultured cells and processed via OGM. A de novo genome assembly was performed followed by structural variant and CNV calling and annotation, and results were compared to known aberrations from standard-of-care tests (karyotype, FISH, and/or CNV microarray). In total, we analyzed 99 chromosomal aberrations, including seven aneuploidies, 19 deletions, 20 duplications, 34 translocations, six inversions, two insertions, six isochromosomes, one ring chromosome, and four complex rearrangements. Several of these variants encompass complex regions of the human genome involved in repeat-mediated microdeletion/microduplication syndromes. High-resolution OGM reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints. This proof-of-principle study demonstrates the ability of OGM to detect nearly all types of chromosomal aberrations. We also suggest suited filtering strategies to prioritize clinically relevant aberrations and discuss future improvements. These results highlight the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and structural variants, which could give rise to an era of "next-generation cytogenetics."


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Mapeamento Cromossômico/métodos , Análise Citogenética/métodos , Variações do Número de Cópias de DNA , Genoma Humano , Análise em Microsséries/métodos , Transtornos Cromossômicos/genética , Humanos , Cariotipagem
7.
Am J Hum Genet ; 108(8): 1423-1435, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237281

RESUMO

Somatic structural variants (SVs) are important drivers of cancer development and progression. In a diagnostic set-up, especially for hematological malignancies, the comprehensive analysis of all SVs in a given sample still requires a combination of cytogenetic techniques, including karyotyping, FISH, and CNV microarrays. We hypothesize that the combination of these classical approaches could be replaced by optical genome mapping (OGM). Samples from 52 individuals with a clinical diagnosis of a hematological malignancy, divided into simple (<5 aberrations, n = 36) and complex (≥5 aberrations, n = 16) cases, were processed for OGM, reaching on average: 283-fold genome coverage. OGM called a total of 918 high-confidence SVs per sample, of which, on average, 13 were rare and >100 kb. In addition, on average, 73 CNVs were called per sample, of which six were >5 Mb. For the 36 simple cases, all clinically reported aberrations were detected, including deletions, insertions, inversions, aneuploidies, and translocations. For the 16 complex cases, results were largely concordant between standard-of-care and OGM, but OGM often revealed higher complexity than previously recognized. Detailed technical comparison with standard-of-care tests showed high analytical validity of OGM, resulting in a sensitivity of 100% and a positive predictive value of >80%. Importantly, OGM resulted in a more complete assessment than any previous single test and most likely reported the most accurate underlying genomic architecture (e.g., for complex translocations, chromoanagenesis, and marker chromosomes). In conclusion, the excellent concordance of OGM with diagnostic standard assays demonstrates its potential to replace classical cytogenetic tests as well as to rapidly map novel leukemia drivers.


Assuntos
Aberrações Cromossômicas , Mapeamento Cromossômico/métodos , Análise Citogenética/métodos , Variações do Número de Cópias de DNA , Genoma Humano , Neoplasias Hematológicas/diagnóstico , Análise em Microsséries/métodos , Neoplasias Hematológicas/genética , Humanos , Cariotipagem
8.
Nat Biomed Eng ; 5(7): 749-758, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34272524

RESUMO

Stretchable wearable devices for the continuous monitoring of physiological signals from deep tissues are constrained by the depth of signal penetration and by difficulties in resolving signals from specific tissues. Here, we report the development and testing of a prototype skin-conformal ultrasonic phased array for the monitoring of haemodynamic signals from tissues up to 14 cm beneath the skin. The device allows for active focusing and steering of ultrasound beams over a range of incident angles so as to target regions of interest. In healthy volunteers, we show that the phased array can be used to monitor Doppler spectra from cardiac tissues, record central blood flow waveforms and estimate cerebral blood supply in real time. Stretchable and conformal skin-worn ultrasonic phased arrays may open up opportunities for wearable diagnostics.


Assuntos
Hemodinâmica/fisiologia , Monitorização Fisiológica/métodos , Circulação Cerebrovascular/fisiologia , Coração/fisiologia , Humanos , Análise em Microsséries , Monitorização Fisiológica/instrumentação , Razão Sinal-Ruído , Ultrassonografia Doppler , Dispositivos Eletrônicos Vestíveis
9.
Nat Biomed Eng ; 5(7): 702-712, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34211146

RESUMO

Assays for the molecular detection of nucleic acids are typically constrained by the level of multiplexing (this is the case for the quantitative polymerase chain reaction (qPCR) and for isothermal amplification), turnaround times (as with microarrays and next-generation sequencing), quantification accuracy (isothermal amplification, microarrays and nanopore sequencing) or specificity for single-nucleotide differences (microarrays and nanopore sequencing). Here we show that a portable and battery-powered PCR assay performed in a toroidal convection chamber housing a microarray of fluorescently quenched oligonucleotide probes allows for the rapid and sensitive quantification of multiple DNA targets with single-nucleotide discrimination. The assay offers a limit of detection of 10 DNA copies within 30 min of turnaround time and a dynamic range spanning 4 orders of magnitude of DNA concentration, and we show its performance by detecting 20 genomic loci and 30 single-nucleotide polymorphisms in human genomic DNA samples, and 15 bacterial species in clinical isolates. Portable devices for the fast and highly multiplexed detection of nucleic acids may offer advantages in point-of-care diagnostics.


Assuntos
DNA/análise , Reação em Cadeia da Polimerase/métodos , Bactérias/genética , Bactérias/isolamento & purificação , DNA/metabolismo , Sondas de DNA/metabolismo , Corantes Fluorescentes/química , Genoma Humano , Genótipo , Humanos , Limite de Detecção , Análise em Microsséries , Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/instrumentação , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes
10.
Aging (Albany NY) ; 13(13): 17328-17336, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34198263

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the human tissues and very stable within cells, exosomes and body fluids. In this study, we aimed to screen the plasma cell-free derived circRNAs in laryngeal squamous cell carcinoma (LSCC) and investigate whether these circRNAs could predicted LSCC as potential biomarkers. METHODS: The circRNA microarray was employed with three samples in each group to screen the dysregulated circRNAs isolated from plasma samples. The top 20 circRNAs were first selected as candidates with the upregulated level in the plasma of LSCC. RESULTS: Further validation found that only circ_0019201, circ_0011773 and circ_0122790 was consistent with training set. The ROC curve also revealed a high diagnostic ability an area under ROC curve value (AUC) for single circRNA and combined. The AUC for circ_0019201, circ_0011773 and circ_0122790 and the combined was 0.933, 0.908, 0.965 and 0.990 in training set. For the validation set, the AUC was 0.766, 0.864, 0.908 and 0.951. The three circRNAs were further investigated with stable expression in human plasma samples. CONCLUSIONS: The plasma derived circ_0019201, circ_0011773 and circ_0122790 might be the potential biomarker for predicting the LSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Impressões Digitais de DNA/métodos , Neoplasias Laríngeas/genética , RNA Circular/genética , Adulto , Idoso , Biomarcadores Tumorais , Estudos de Casos e Controles , Ácidos Nucleicos Livres , Feminino , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos
11.
Toxicology ; 458: 152848, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34217791

RESUMO

High maternal serum bile acid level is common and sometimes harmful to the gravida. This study aimed to confirm the bile acid phenotypic change caused by prenatal ethanol exposure (PEE) and elucidate its placental mechanism. Pregnant Wistar rats were administered intragastrically with ethanol 4 g/kg⋅d from gestational day 9-20. Total bile acids (TBA) were detected in maternal, fetal serum and placental tissues, increasing significantly in the serum but no significant change in the placental tissues. Meta-analysis was performed and verified the efficacy of the PEE-induced model based on published data from several relevant studies. Mining of microarray data from human and rat placental sources identified the involvement of bile acid metabolism and its significant genes, which were verified by RT-qPCR and western blotting on tissues and treated BeWo cells with the administration of FXR/PXR siRNAs or FXR/PXR agonists. Our examination, consistent with microarray data and wet experiments, showed that organic anion transporter polypeptide-related protein 2B1 (Oatp2b1), multidrug resistance-associated proteins 3 (Mrp3) and breast cancer resistance protein (Bcrp) expression were increased, while nuclear receptor farnesoid X receptor (Fxr) was decreased but pregnane X receptor (Pxr) was increased. Furthermore, the interventional experiments confirmed that FXR regulated Bcrp while PXR regulated Oatp2b1 and Mrp3. In summary, PEE could induce high bile acid level in maternal serum and its mechanism is associated with the high expression of BCRP/MRP3/OATP2B1 in the placenta through up-regulating PXR and down-regulating FXR, thereby leading to an excessive bile acid transport to maternal blood via the placenta. Our study provides a novel perspective in terms of placenta, explaining the increased maternal blood bile acids under the toxicity of PEE.


Assuntos
Ácidos e Sais Biliares/metabolismo , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Placenta/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Proteínas de Transporte/metabolismo , Linhagem Celular , Mineração de Dados , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Gravidez , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares
12.
BMC Genomics ; 22(1): 574, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315441

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are a growing focus in cancer research. Deciphering pathways influenced by lncRNAs is important to understand their role in cancer. Although knock-down or overexpression of lncRNAs followed by gene expression profiling in cancer cell lines are established approaches to address this problem, these experimental data are not available for a majority of the annotated lncRNAs. RESULTS: As a surrogate, we present lncGSEA, a convenient tool to predict the lncRNA associated pathways through Gene Set Enrichment Analysis of gene expression profiles from large-scale cancer patient samples. We demonstrate that lncGSEA is able to recapitulate lncRNA associated pathways supported by literature and experimental validations in multiple cancer types. CONCLUSIONS: LncGSEA allows researchers to infer lncRNA regulatory pathways directly from clinical samples in oncology. LncGSEA is written in R, and is freely accessible at https://github.com/ylab-hi/lncGSEA .


Assuntos
Neoplasias , RNA Longo não Codificante , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries , Neoplasias/genética , RNA Longo não Codificante/genética , Transcriptoma
13.
Methods Mol Biol ; 2328: 1-11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34251616

RESUMO

Recent progress in transcriptomics and co-expression networks have enabled us to predict the inference of the biological functions of genes with the associated environmental stress. Microarrays and RNA sequencing (RNA-seq) are the most commonly used high-throughput gene expression platforms for detecting differentially expressed genes between two (or more) phenotypes. Gene co-expression networks (GCNs) are a systems biology method for capturing transcriptional patterns and predicting gene interactions into functional and regulatory relationships. Here, we describe the procedures and tools used to construct and analyze GCN and investigate the integration of transcriptional data with GCN to provide reliable information about the underlying biological mechanism.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Análise em Microsséries/métodos , Algoritmos , Arabidopsis , Ontologia Genética , Fenótipo , Análise de Componente Principal , Mapas de Interação de Proteínas , Software
14.
JCI Insight ; 6(13)2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34081630

RESUMO

BACKGROUNDThe role of humoral immunity in COVID-19 is not fully understood, owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome.METHODSUsing SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients' plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution.RESULTSWe identified linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S-811-825, S-881-895, and N-156-170 epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes.CONCLUSIONEpitope-resolved antibody testing not only affords a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats.FUNDINGOntario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund.


Assuntos
Testes de Aglutinação/métodos , Formação de Anticorpos/imunologia , Teste Sorológico para COVID-19/métodos , COVID-19/imunologia , Epitopos de Linfócito B/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , COVID-19/sangue , COVID-19/mortalidade , Epitopos/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Humanos , Imunidade Humoral , Análise em Microsséries/métodos , Nucleocapsídeo/química , Nucleocapsídeo/genética , Nucleocapsídeo/imunologia , Peptídeos/imunologia , SARS-CoV-2/genética , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Methods Mol Biol ; 2268: 21-42, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34085259

RESUMO

A workflow is described for assaying the expression of G protein-coupled receptors (GPCRs) in cultured cells, using a combination of methods that assess GPCR mRNAs. Beginning from the isolation of cDNA and preparation of mRNA, we provide protocols for designing and testing qPCR primers, assaying mRNA expression using qPCR and high-throughput analysis of GPCR mRNA expression via TaqMan qPCR-based, GPCR-selective arrays. We also provide a workflow for analysis of expression from RNA-sequencing (RNA-seq) assays, which can be queried to yield expression of GPCRs and related genes in samples of interest, as well as to test changes in expression between groups, such as in cells treated with drugs or from healthy and diseased subjects. We place priority on optimized protocols that distinguish signal from noise, as GPCR mRNAs are typically present in low abundance, necessitating techniques that maximize sensitivity while minimizing noise. These methods may also be applicable for assessing the expression of members of families of other low abundance genes via high-throughput analyses of mRNAs, followed by independent confirmation and validation of results via qPCR.


Assuntos
Análise em Microsséries/métodos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores Acoplados a Proteínas G/metabolismo , Análise de Sequência de RNA/métodos , Humanos , Cultura Primária de Células , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/genética
16.
Nat Commun ; 12(1): 3707, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140478

RESUMO

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600E PtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.


Assuntos
Carcinogênese/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Proteínas de Homeodomínio/metabolismo , Melanoma/metabolismo , Fatores do Domínio POU/metabolismo , Neoplasias Cutâneas/metabolismo , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Estudos de Coortes , Variações do Número de Cópias de DNA , Progressão da Doença , Técnicas de Silenciamento de Genes , Haploinsuficiência , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise em Microsséries , Fator de Transcrição Associado à Microftalmia/metabolismo , Mutação , Fatores do Domínio POU/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , RNA Interferente Pequeno , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/secundário
17.
Viruses ; 13(5)2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063445

RESUMO

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and -negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze.


Assuntos
Alérgenos/imunologia , Anticorpos Antivirais/imunologia , Infecções por Picornaviridae/imunologia , Sons Respiratórios/imunologia , Rhinovirus/imunologia , Alérgenos/genética , Antígenos Virais/genética , Antígenos Virais/imunologia , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Masculino , Análise em Microsséries , Infecções por Picornaviridae/virologia , Rhinovirus/genética , Rhinovirus/fisiologia
18.
Anal Methods ; 13(28): 3127-3135, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180923

RESUMO

Obesity is a key component of metabolic syndrome and is precipitated by complex interactions between multiple environmental and genetic factors. The integration of multi-level bioinformation is needed to understand the altered endogenous molecule and metabolic mechanisms. In this study, an integrated analytical strategy was proposed by combining microarray data from a gene expression omnibus database and in vitro serum metabolomic data to unearth bioinformation associated with cafeteria diet induced obesity. In the diet induced obese rats, 23 genes and 9 metabolites showed significant changes, in which the increased levels of alanine, lactate and lactate dehydrogenase B (Ldhb) and the decreased levels of citrate and pyruvate indicated an enhanced glycolysis and a disordered Krebs cycle. Furthermore, the closeness centrality of Slc27a2, Apobr, alanine and histidine in the correlations network of pathways, genes and metabolites was 0.5036, 0.5111, 0.5702, and 0.5352, respectively. These close links between metabolites and genes would be highly useful to assess the degree of obesity and to understand the developmental mechanism of obesity. The pathway enrichment analysis of genes and metabolites proved that a disturbed glucose metabolism and biosynthesis of amino acids are typical metabolic features of cafeteria-induced obesity. The metabolomics combined with microarray data not only could identify the biomarkers, but also would be beneficial to the follow-up research of obesity treatment, especially providing a methodological basis for the study of other diseases.


Assuntos
Síndrome Metabólica , Obesidade , Animais , Coenzima A Ligases , Dieta , Metabolômica , Análise em Microsséries , Obesidade/etiologia , Ratos
19.
Nat Med ; 27(6): 1097-1104, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34083811

RESUMO

Around 5% of the population is affected by a rare genetic disease, yet most endure years of uncertainty before receiving a genetic test. A common feature of genetic diseases is the presence of multiple rare phenotypes that often span organ systems. Here, we use diagnostic billing information from longitudinal clinical data in the electronic health records (EHRs) of 2,286 patients who received a chromosomal microarray test, and 9,144 matched controls, to build a model to predict who should receive a genetic test. The model achieved high prediction accuracies in a held-out test sample (area under the receiver operating characteristic curve (AUROC), 0.97; area under the precision-recall curve (AUPRC), 0.92), in an independent hospital system (AUROC, 0.95; AUPRC, 0.62), and in an independent set of 172,265 patients in which cases were broadly defined as having an interaction with a genetics provider (AUROC, 0.9; AUPRC, 0.63). Patients carrying a putative pathogenic copy number variant were also accurately identified by the model. Compared with current approaches for genetic test determination, our model could identify more patients for testing while also increasing the proportion of those tested who have a genetic disease. We demonstrate that phenotypic patterns representative of a wide range of genetic diseases can be captured from EHRs to systematize decision-making for genetic testing, with the potential to speed up diagnosis, improve care and reduce costs.


Assuntos
Variações do Número de Cópias de DNA/genética , Doenças Genéticas Inatas/diagnóstico , Testes Genéticos , Doenças Raras/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Feminino , Doenças Genéticas Inatas/patologia , Humanos , Lactente , Masculino , Análise em Microsséries , Fenótipo , Doenças Raras/genética , Doenças Raras/patologia
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 541-544, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096021

RESUMO

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION: CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.


Assuntos
Diagnóstico Pré-Natal , Feminino , Humanos , Cariotipagem , Análise em Microsséries , Gravidez , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...