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1.
Nat Commun ; 11(1): 4873, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978376

RESUMO

Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Epigenômica/métodos , RNA Mensageiro/metabolismo , Transcriptoma , Encéfalo/metabolismo , Metilação de DNA , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genômica , Histonas/metabolismo , Humanos , MicroRNAs
2.
Adv Exp Med Biol ; 1255: 51-62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949389

RESUMO

DNA methylations, including global methylation pattern and specific gene methylation, are associated with pathogenesis and progress of pulmonary fibrosis. This chapter illustrates alteration of DNA methylation in pulmonary fibrosis as a predictive or prognostic factor. Treatment with the DNA methylation inhibitors will be an emerging anti-fibrosis therapy, although we are still in the pre-clinical stage of using epigenetic markers as potential targets for biomarkers and therapeutic interventions.


Assuntos
Metilação de DNA , Fibrose Pulmonar/genética , Epigenômica , Humanos
3.
Adv Exp Med Biol ; 1255: 63-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949390

RESUMO

This chapter overviews roles of DNA methylation in inflammatory cell biology with the focuses on lymphocytes and macrophages/monocytes in lung diseases, although the molecular mechanisms by which target genes are methylated and regulated in lung diseases remain unclear. Most of epigenetic studies on DNA methylation of target genes in lung diseases mainly demonstrated the correlation of DNA methylation of target genes with the levels of other corresponding factors, with the specificity of clinical phenomes, and with the severity of lung diseases. There is an urgent need to identify and validate the specificity and regulatory mechanisms of inflammatory cell epigenetics in depth. The epigenetic heterogeneity among different subsets of T cells and among promoters or non-promoters of target genes should be furthermore clarified in acute or chronic lung diseases and cancers. The hyper/hypo-methylation and modifications of chromosol and extrachromosomal DNA may result in alternations in proteins within inflammatory cells, which can be identified as disease-specific biomarkers and therapeutic targets.


Assuntos
Metilação de DNA , Inflamação/genética , Pneumopatias/genética , Pneumopatias/patologia , Epigênese Genética , Epigenômica , Humanos
4.
Adv Exp Med Biol ; 1255: 73-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949391

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic complex lung disease with no specific treatment and poor prognosis, characterized by the pulmonary progressive fibrosis and dysfunctions that lead to respiratory failure. Several factors may impact the progress of IPF, including age, cigarette smoking, and dusts, of which genetic and epigenetic factors mainly contribute to lung tissue fibrosis. DNA methylation is one of epigenetic processes that occur in many diseases and regulate chromosomal and extrachromosomal DNA functions in response to environmental exposures. The methylation plays pivotal roles in regulation of gene expression to facilitate the formation of fibroblastic foci and lung fibrosis. This chapter will describe alterations and effects of the DNA methylation on gene expression, the potential application of DNA methylation as a biomarker, and significance as therapeutic targets. Those understanding will provide us new insight into the treatment and prognosis of IPF.


Assuntos
Metilação de DNA , Fibrose Pulmonar Idiopática/genética , Epigênese Genética , Epigenômica , Expressão Gênica , Humanos
5.
Adv Exp Med Biol ; 1255: 83-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949392

RESUMO

Chronic obstructive pulmonary disease (COPD) is a lung disease affected by both genetic and environmental factors. Therefore, the role of epigenetics in the pathogenesis of COPD has attracted much attention. As one of the three epigenetic mechanisms, DNA methylation has been extensively studied in COPD. The present review aims at overviewing the effect of DNA methylation on etiology, pathogenesis, pathophysiological changes, and complications of COPD. The clarification of aberrant methylation of target genes, which play important roles in the initiation and progression of COPD, will provide new disease-specific biomarker and targets for early diagnosis and therapy.


Assuntos
Metilação de DNA , Doença Pulmonar Obstrutiva Crônica/genética , Epigênese Genética , Epigenômica , Humanos
6.
Nat Commun ; 11(1): 4782, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963223

RESUMO

Polycomb and Trithorax group proteins maintain stable epigenetic memory of gene expression states for some genes, but many targets show highly dynamic regulation. Here we combine experiment and theory to examine the mechanistic basis of these different modes of regulation. We present a mathematical model comprising a Polycomb/Trithorax response element (PRE/TRE) coupled to a promoter and including Drosophila developmental timing. The model accurately recapitulates published studies of PRE/TRE mediated epigenetic memory of both silencing and activation. With minimal parameter changes, the same model can also recapitulate experimental data for a different PRE/TRE that allows dynamic regulation of its target gene. The model predicts that both cell cycle length and PRE/TRE identity are critical for determining whether the system gives stable memory or dynamic regulation. Our work provides a simple unifying framework for a rich repertoire of PRE/TRE functions, and thus provides insights into  genome-wide Polycomb/Trithorax regulation.


Assuntos
Proteínas Cromossômicas não Histona/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Epigenômica , Regulação da Expressão Gênica no Desenvolvimento/genética , Modelos Teóricos , Complexo Repressor Polycomb 1/genética , Animais , Divisão Celular , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Epigênese Genética , Feminino , Inativação Gênica , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Regiões Promotoras Genéticas , Elementos de Resposta
7.
Nat Commun ; 11(1): 4779, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963246

RESUMO

Highly reproducible smoking-associated DNA methylation changes in whole blood have been reported by many Epigenome-Wide-Association Studies (EWAS). These epigenetic alterations could have important implications for understanding and predicting the risk of smoking-related diseases. To this end, it is important to establish if these DNA methylation changes happen in all blood cell subtypes or if they are cell-type specific. Here, we apply a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven large EWAS. We find that most of the highly reproducible smoking-associated hypomethylation signatures are more prominent in the myeloid lineage. A meta-analysis further identifies a myeloid-specific smoking-associated hypermethylation signature enriched for DNase Hypersensitive Sites in acute myeloid leukemia. These results may guide the design of future smoking EWAS and have important implications for our understanding of how smoking affects immune-cell subtypes and how this may influence the risk of smoking related diseases.


Assuntos
Metilação de DNA/efeitos dos fármacos , Epigenoma , Fumar/efeitos adversos , Algoritmos , Grupo com Ancestrais do Continente Asiático , Sangue , Ilhas de CpG , Epigenômica/métodos , Grupos Étnicos , Feminino , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Células Mieloides
8.
Nat Commun ; 11(1): 4803, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968068

RESUMO

Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Perfilação da Expressão Gênica/métodos , Heterogeneidade Genética , Imagem por Ressonância Magnética/métodos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Idoso , Antígenos CD/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Caderinas/genética , Imagem de Difusão por Ressonância Magnética/métodos , Epigenômica , Feminino , Marcadores Genéticos , Genômica , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética , Transcriptoma
9.
Clin Epigenetics ; 12(1): 118, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758273

RESUMO

Coronaviruses (CoVs) are highly diverse single-stranded RNA viruses owing to their susceptibility to numerous genomic mutations and recombination. Such viruses involve human and animal pathogens including the etiologic agents of acute respiratory tract illnesses: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the highly morbific SARS-CoV-2. Coronavirus disease 2019 (COVID-19), an emerging disease with a quick rise in infected cases and deaths, was recently identified causing a worldwide pandemic. COVID-19 disease outcomes were found to increase in elderly and patients with a compromised immune system. Evidences indicated that the main culprit behind COVID-19 deaths is the cytokine storm, which is illustrated by an uncontrolled over-production of soluble markers of inflammation. The regulation process of coronavirus pathogenesis through molecular mechanism comprise virus-host interactions linked to viral entry, replication and transcription, escape, and immune system control. Recognizing coronavirus infections and COVID-19 through epigenetics lens will lead to potential alteration in gene expression thus limiting coronavirus infections. Focusing on epigenetic therapies reaching clinical trials, clinically approved epigenetic-targeted agents, and combination therapy of antivirals and epigenetic drugs is currently considered an effective and valuable approach for viral replication and inflammatory overdrive control.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Epigenômica/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Descoberta de Drogas/métodos , Genoma Viral/efeitos dos fármacos , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia
10.
Nat Commun ; 11(1): 4206, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826896

RESUMO

Saccharomyces cerevisiae TBP associated factor 14 (Taf14) is a well-studied transcriptional regulator that controls diverse physiological processes and that physically interacts with at least seven nuclear complexes in yeast. Despite multiple previous Taf14 structural studies, the nature of its disparate transcriptional regulatory functions remains opaque. Here, we demonstrate that the extra-terminal (ET) domain of Taf14 (Taf14ET) recognizes a common motif in multiple transcriptional coactivator proteins from several nuclear complexes, including RSC, SWI/SNF, INO80, NuA3, TFIID, and TFIIF. Moreover, we show that such partner binding promotes liquid-liquid phase separation (LLPS) of Taf14ET, in a mechanism common to YEATS-associated ET domains (e.g., AF9ET) but not Bromo-associated ET domains from BET-family proteins. Thus, beyond identifying the molecular mechanism by which Taf14ET associates with many transcriptional regulators, our study suggests that Taf14 may function as a versatile nuclear hub that orchestrates transcriptional machineries to spatiotemporally regulate diverse cellular pathways.


Assuntos
Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Fator de Transcrição TFIID/metabolismo , Proteínas de Transporte , Proteínas de Ciclo Celular/metabolismo , Análise por Conglomerados , Proteínas de Ligação a DNA , Epigenômica , Regulação Fúngica da Expressão Gênica , Modelos Moleculares , Proteínas Nucleares/metabolismo , Ligação Proteica , Conformação Proteica , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Fator de Transcrição TFIID/química , Fator de Transcrição TFIID/genética , Fatores de Transcrição/metabolismo
11.
Nat Commun ; 11(1): 4079, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796936

RESUMO

DNA methylation is an epigenetic modification that specifies the basic state of pluripotent stem cells and regulates the developmental transition from stem cells to various cell types. In flowering plants, the shoot apical meristem (SAM) contains a pluripotent stem cell population which generates the aerial part of plants including the germ cells. Under appropriate conditions, the SAM undergoes a developmental transition from a leaf-forming vegetative SAM to an inflorescence- and flower-forming reproductive SAM. While SAM characteristics are largely altered in this transition, the complete picture of DNA methylation remains elusive. Here, by analyzing whole-genome DNA methylation of isolated rice SAMs in the vegetative and reproductive stages, we show that methylation at CHH sites is kept high, particularly at transposable elements (TEs), in the vegetative SAM relative to the differentiated leaf, and increases in the reproductive SAM via the RNA-dependent DNA methylation pathway. We also show that half of the TEs that were highly methylated in gametes had already undergone CHH hypermethylation in the SAM. Our results indicate that changes in DNA methylation begin in the SAM long before germ cell differentiation to protect the genome from harmful TEs.


Assuntos
Metilação de DNA , Meristema/crescimento & desenvolvimento , Meristema/genética , Oryza/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/genética , Elementos de DNA Transponíveis , Biologia do Desenvolvimento , Epigenômica , Flores , Regulação da Expressão Gênica de Plantas , Inflorescência , Folhas de Planta/metabolismo , Proteínas de Plantas/genética
13.
Revista Digital de Postgrado ; 9(2): 217, ago. 2020. ilus, graf
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1103536

RESUMO

Los primeros mil días de vida son parte del Curso de Vida, al tomar en consideración la Epigenética, término postulado por Waddington en 1942: modifica la expresión genética SIN cambiar la secuencia de las bases de ADN. El proyecto internacional llamado DOHaD (Developmental Origins of Health and Disease) u ODSE (Orígenes del Desarrollo de la Salud y Enfermedad), está inserto dentro de la Transición Alimentaria y Nutricional (TAN), que, en países en desarrollo­ocurre en forma muy rápida ­produce tanto la malnutrición por déficit como por exceso; es decir la doble carga nutricional. La TAN es producto en nuestro país, de una urbanización acelerada y anárquica, y de cambios socioculturales, como la incorporación de la mujer al mercado de trabajo con menos tiempo para cocinar; está acompañada de una transición epidemiológica con la emergencia y prevalencia de la obesidad y de las enfermedades crónicas como morbiletalidad. Esta doble carga nutricional se modificó, por la situación país, y prevalece más el déficit que el exceso. Se presenta el PROYECTO FUNDACIÓN BENGOA ­ SVPP ­ SOGV ­ CANIA, cuya meta es: Elaborar una agenda preventiva común contra la malnutrición tanto por déficit como por exceso y sus comorbilidades, bajo el enfoque de los primeros mil días de vida y su efecto sobre todo el curso de vida. Se realizó el diseño y aplicación de tres cuestionarios digitales, que se utilizaran para la elaboración de esta meta. Se consolidó un CONSENSO NACIONAL formado por profesionales de la salud involucrados en los primeros mil días de vida(AU)


The first 1000 days of life is the new paradigm that determines health and nutrition during the life course, based on epidemiological models that incorporate the concept of Epigenetics, term introduced by Waddington, that refers to changes that affect the genetic expression without changing the DNA sequence, within the international program DOHaD/ODSE as well as the Food and Nutrition Transition(FNT). This FNT, product of an accelerated and anarchic urbanization that led to sedentary activities, plus the incorporation of women to the work media, with less time for cooking, with the substitution of the traditional diet for one much more practical and efficient in time and effort. It is accompanied by demographic and epidemiologic changes and transitions. The Double Burden of Nutrition in VENEZUELA has changed due to the effect of the recent crisis with a rise in malnutrition and a fall in obesity/overweight. The current project: Fundación Bengoa- Pediatric Society Venezuela (SVPP) ­ CANIA - Obstetric Society of Venezuela (SOGV) is called Developmental Origins of Health and Disease in Venezuela (DOHaD Venezuela): and by means of a national consensus of medical societies and institutions, its goal is "To elaborate a Preventive Agenda both for Malnutrition and for Overweight and Obesity and its comorbidities, considering the First 1000 Days of life and its effect over the life course"


Assuntos
Humanos , Masculino , Feminino , Gravidez na Adolescência , Características da População , Recém-Nascido de Baixo Peso , Mortalidade Materna , Epigenômica , Doenças Cardiovasculares , Epidemiologia , Desnutrição , Transição Nutricional
14.
Am J Bot ; 107(8): 1097-1100, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32737992
15.
Mol Cell ; 79(3): 368-370, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32763225

RESUMO

A recent study (Sulkowski et al., 2020) reveals that oncometabolites, which are produced by metabolic gene mutations in many cancers, sensitize cells to PARP inhibition by antagonizing histone demethylation and obscuring epigenetic marks that are necessary for efficient DNA repair.


Assuntos
Dano ao DNA , Neoplasias/genética , Reparo do DNA , Epigênese Genética , Epigenômica , Humanos
17.
Arch. argent. pediatr ; 118(4): s118-s129, agosto 2020.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1118605

RESUMO

En las últimas décadas, las enfermedades crónicas no transmisibles (ENT) se han convertido en la principal causa de mortalidad global y han aumentado en América Latina. La contribución de recursos de la ciencia del desarrollo, la epigenética, las neurociencias, las ciencias ambientales, la epidemiología y la investigación ha generado evidencia del origen de las ENT desde la programación fetal. Los resultados de salud y enfermedad devienen de una trayectoria dinámica en la que se agregan factores protectores para una vida saludable o factores de riesgo para enfermedades del individuo y las comunidades.El concepto de Developmental Origins of Health and Disease redimensiona el papel del equipo de salud materno-infantil y debe guiar las políticas públicas para priorizar los primeros mil días de vida para un desarrollo saludable y la prevención de ENT. Se presenta una actualización sobre las principales condiciones ambientales adversas que pueden alterar la programación del desarrollo y predisponer a ENT en el curso de la vida.


In recent decades, chronic non-communicable diseases (NCDs) have become the leading cause of global mortality and increased in Latin America. The contribution of the resources from development science, epigenetics, neurosciences, environmental sciences, epidemiology and research has generated evidence of the origin of NCDs since fetal programming. The healt and disease outcomes result from a dynamic trajectory where protective factors are added for a healthy life or risk factors for diseases of the individual and the communities. Developmental Origins of Health and Disease concept resizes the role of the maternal and child health team and should guide public policies by prioritizing the first 1000 days of life for healthy development and NCDs prevention. We present an update on principal adverse environmental conditions that may alter development programming and predispose NCDs in life course


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Meio Ambiente , Doenças não Transmissíveis/epidemiologia , Desenvolvimento Infantil , Saúde Pública , Saúde Materno-Infantil , Exposição Ambiental , Epigenômica , Doenças não Transmissíveis/prevenção & controle
18.
BMC Bioinformatics ; 21(1): 268, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600298

RESUMO

BACKGROUND: High-throughput technologies enable the cost-effective collection and analysis of DNA methylation data throughout the human genome. This naturally entails missing values management that can complicate the analysis of the data. Several general and specific imputation methods are suitable for DNA methylation data. However, there are no detailed studies of their performances under different missing data mechanisms -(completely) at random or not- and different representations of DNA methylation levels (ß and M-value). RESULTS: We make an extensive analysis of the imputation performances of seven imputation methods on simulated missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR) methylation data. We further consider imputation performances on the popular ß- and M-value representations of methylation levels. Overall, ß-values enable better imputation performances than M-values. Imputation accuracy is lower for mid-range ß-values, while it is generally more accurate for values at the extremes of the ß-value range. The MAR values distribution is on the average more dense in the mid-range in comparison to the expected ß-value distribution. As a consequence, MAR values are on average harder to impute. CONCLUSIONS: The results of the analysis provide guidelines for the most suitable imputation approaches for DNA methylation data under different representations of DNA methylation levels and different missing data mechanisms.


Assuntos
Metilação de DNA , Coleta de Dados , Epigenômica/métodos , Humanos
19.
PLoS Comput Biol ; 16(7): e1008050, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687525

RESUMO

Machine learning algorithms trained to predict the regulatory activity of nucleic acid sequences have revealed principles of gene regulation and guided genetic variation analysis. While the human genome has been extensively annotated and studied, model organisms have been less explored. Model organism genomes offer both additional training sequences and unique annotations describing tissue and cell states unavailable in humans. Here, we develop a strategy to train deep convolutional neural networks simultaneously on multiple genomes and apply it to learn sequence predictors for large compendia of human and mouse data. Training on both genomes improves gene expression prediction accuracy on held out and variant sequences. We further demonstrate a novel and powerful approach to apply mouse regulatory models to analyze human genetic variants associated with molecular phenotypes and disease. Together these techniques unleash thousands of non-human epigenetic and transcriptional profiles toward more effective investigation of how gene regulation affects human disease.


Assuntos
Regulação da Expressão Gênica , Variação Genética , Aprendizado de Máquina , Algoritmos , Animais , Biologia Computacional , Bases de Dados Genéticas , Epigenômica , Genoma Humano , Genômica , Hepatócitos/metabolismo , Humanos , Camundongos , Modelos Genéticos , Modelos Estatísticos , Mutação , Redes Neurais de Computação , Locos de Características Quantitativas , Análise de Sequência de DNA , Software , Especificidade da Espécie
20.
Nat Commun ; 11(1): 3475, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694610

RESUMO

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.


Assuntos
DNA Tumoral Circulante/sangue , Detecção Precoce de Câncer/métodos , Neoplasias/sangue , Neoplasias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , China , Metilação de DNA , Epigenômica , Feminino , Marcadores Genéticos , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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