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2.
JAMA Netw Open ; 4(1): e2034569, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33502483

RESUMO

Importance: Acute respiratory distress syndrome (ARDS) confers high mortality risk among critically ill patients. Identification of biomarkers associated with ARDS risk may guide clinical diagnosis and prognosis. Objective: To systematically evaluate the association of blood metabolites with ARDS risk and survival. Design, Setting, and Participants: In this cohort study, data from the Molecular Epidemiology of ARDS (MEARDS) study, a prospective cohort of 403 patients with ARDS and 1227 non-ARDS controls, were analyzed. Patients were recruited in intensive care units (ICUs) at Massachusetts General Hospital and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts, from January 1, 1998, to December 31, 2014. Data analysis was performed from December 9, 2018, to January 4, 2019. Main Outcomes and Measures: Participants were followed up daily for ARDS development defined by Berlin criteria, requiring fulfillment of chest radiograph and oxygenation criteria on the same calendar day during invasive ventilatory assistance. A 2-stage study design was used to explore novel metabolites associated with ARDS risk and survival. Results: Of the 1630 participants from MEARDS who were admitted to the ICU , 403 (24.7%) were diagnosed with ARDS (mean [SD] age, 63.0 [17.0] years; 251 [62.3%] male) and 1227 (75.3%) were at-risk but did not have ARDS (mean [SD] age, 62.3 [16.9] years; 753 [61.4%] male). Mendelian randomization suggested that genetically regulated serum mannose was associated with ARDS risk (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = 7.46 × 10-6) in the discovery stage. In the functional validation stage incorporating 83 participants with ARDS and matched at-risk participants in the control group from the ICU, the protective association of mannose with ARDS risk was validated (OR, 0.67; 95% CI, 0.46-0.97; P = .03). Furthermore, serum mannose was associated with 28-day (OR, 0.25; 95% CI, 0.11-0.56; P = 6.95 × 10-4) and 60-day (OR, 0.36; 95% CI, 0.19-0.71; P = 3.12 × 10-3) mortality and 28-day (hazard ratio, 0.49; 95% CI, 0.32-0.74; P = 6.41 × 10-4) and 60-day (hazard ratio, 0.55; 95% CI, 0.37-0.80; P = 2.11 × 10-3) survival. Conclusions and Relevance: In this study, genetically regulated serum mannose appeared to be associated with ARDS risk and outcome, and increased serum mannose at admission was associated with reduced ARDS risk and better survival. These findings could inform prevention and clinical intervention in ARDS cases, which have increased with the expansion of the coronavirus disease 2019 pandemic.


Assuntos
Manose/sangue , /mortalidade , APACHE , Idoso , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco
3.
Chest ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189655

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a devastating syndrome with heterogeneous subtypes, but few causal biomarkers have been identified. RESEARCH QUESTION: Would multi-stage Mendelian randomization identify new causal protein biomarkers for ARDS 28-day mortality? STUDY DESIGN AND METHODS: Three hundred moderate to severe ARDS patients were randomly selected from the Molecular Epidemiology of ARDS (MEARDS) cohort for proteomics analysis. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was applied to detect the association between proteins and ARDS 28-day mortality. Candidate proteins were analyzed using generalized summary data-based Mendelian randomization (GSMR). Protein quantitative trait summary statistics were retrieved from the INTERVAL study (n=2,504), and a genome-wide association study for ARDS was conducted from the Identification of SNPs Predisposing to Altered Acute Lung Injury Risk (iSPAAR) consortium study (n=534). Causal mediation analysis detected the role of platelet count in mediating the effect of protein on ARDS prognosis. RESULTS: Plasma IGFBP7 moderately increased ARDS 28-day mortality [Odd Ratio (OR)=1·11, 95%CI=1·04-1·19, P=1·80×10-3] per log2-increase. GSMR analysis coupled with four other Mendelian randomization methods revealed IGFBP7 as a causal biomarker for ARDS 28-day mortality (OR=2·61, 95%CI=1·33-5·13, P=5·31×10-3). Causal mediation analysis indicated that the association between IGFBP7 and ARDS 28-day mortality is mediated by platelet count (OR=1·03, 95%CI=1·02-1·04, P=0·01). INTERPRETATION: We identified plasma IGFBP7 as a novel causal protein involved in the pathogenesis of ARDS 28-day mortality and platelet function in ARDS, a topic for further experimental and clinical investigation.

4.
BMC Plant Biol ; 20(1): 515, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176702

RESUMO

BACKGROUND: Stalk fracture caused by strong wind can severely reduce yields in maize. Stalks with higher stiffness and flexibility will exhibit stronger lodging resistance. However, stalk flexibility is rarely studied in maize. Stalk fracture of the internode above the ear before tasseling will result in the lack of tassel and pollen, which is devastating for pollination in seed production. In this study, we focused on stalk lodging before tasseling in two maize inbred lines, JING724 and its improved line JING724A1 and their F2:3 population. RESULTS: JING724A1 showed a larger stalk fracture angle than JING724, indicating higher flexibility. In addition, compared to JING724, JING724A1 also had longer and thicker stalks, with a conical, frustum-shaped internode above the ear. Microscopy and X-ray microcomputed tomography of the internal stalk architecture revealed that JING724A1 had more vascular bundles and thicker sclerenchyma tissue. Furthermore, total soluble sugar content of JING724A1, especially the glucose component, was substantially higher than in JING724. Using an F2:3 population derived from a JING724 and JING724A1 cross, we performed bulk segregant analysis for stalk fracture angle and detected one QTL located on Chr3: 14.00-19.28 Mb. Through transcriptome data analysis and ∆ (SNP-index), we identified two candidate genes significantly associated with high stalk fracture angle, which encode a RING/U-box superfamily protein (Zm00001d039769) and a MADS-box transcription factor 54 (Zm00001d039913), respectively. Two KASP markers designed from these two candidate genes also showed significant correlations with stalk fracture angle. CONCLUSIONS: The internode shape and glucose content are possibly correlated with stalk flexibility in maize. Two genes in the detected QTL are potentially associated with stalk fracture angle. These novel phenotypes and associated loci will provide a theoretical foundation for understanding the genetic mechanisms of lodging, and facilitate the selection of maize varieties with improved flexibility and robust lodging resistance.

5.
Ecotoxicol Environ Saf ; 203: 111054, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888616

RESUMO

Quinclorac (3,7-dichloroquinoline-8-carboxylic acid, QNC) is a highly selective auxin herbicide that is typically applied to paddy rice fields. Its residue is a serious problem in crop rotations. In this study, Oryza sativa L. seedlings was used as a model plant to explore its biochemical response to abiotic stress caused by QNC and nZVI coexposure, as well as the interactions between QNC and nZVI treatments. Exposure to 5 and 10 mg/L QNC reduced the fresh biomass by 26.6% and 33.9%, respectively, compared to the control. The presence of 50 and 250 mg/L nZVI alleviated the QNC toxicity, but the nZVI toxicity was aggravated by the coexist of QNC. Root length was enhanced upon exposure to low or medium doses of both QNC and nZVI, whereas root length was inhibited under high-dose coexposure. Both nZVI and QNC, either alone or in combination, significantly inhibited the biosynthesis of chlorophyll, and the inhibition rate increased with elevated nZVI and QNC concentration. It was indicated that nZVI or QNC can affect the plant photosynthesis, and there was a significant interaction between the two treatments. Effects of QNC on the antioxidant response of Oryza sativa L. differed in the shoots and roots; generally, the introduction of 50 and 250 mg/L nZVI alleviated the oxidative stress (POD in shoots, SOD and MDA in roots) induced by QNC. However, 750 mg/kg nZVI seriously damaged Oryza sativa L. seedlings, which likely resulted from active iron deficiency. QNC could be removed from the culture solution by nZVI; as a result, nZVI suppressed QNC uptake by 20%-30%.


Assuntos
Antioxidantes/metabolismo , Ferro/toxicidade , Nanopartículas/toxicidade , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quinolinas/toxicidade , Poluentes do Solo/toxicidade , Transporte Biológico , Biomassa , Clorofila/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
6.
Front Plant Sci ; 11: 1057, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733529

RESUMO

Southern corn rust (SCR) caused by Puccinia polysora Underw. is a major disease causing severe yield losses during maize production. Here, we identified and mapped the SCR resistance gene RppM from the near-isogenic line Kangxiujing2416 (Jing2416K), which harbors RppM in the genetic background of the susceptible inbred line Jing2416. In this study, the inheritance of SCR resistance was investigated in F2 and F3 populations derived from a cross between Jing2416K and Jing2416. The observed 3:1 segregation ratio of resistant to susceptible plants indicated that the SCR resistance is controlled by a single dominant gene. Using an F2 population, we performed bulked segregant analysis (BSA) sequencing and mapped RppM to a 3.69-Mb region on chromosome arm 10S. To further narrow down the region harboring RppM, we developed 13 insertion/deletion (InDel) markers based on the sequencing data. Finally, RppM was mapped to a region spanning 110-kb using susceptible individuals from a large F2 population. Two genes (Zm00001d023265 and Zm00001d023267) encoding putative CC-NBS-LRR (coiled-coiled, nucleotide-binding site, and leucine-rich repeat) proteins, a common characteristic of R genes, were located in this region (B73 RefGen_v4 reference genome). Sequencing and comparison of the two genes cloned from Jing2416K and Jing2416 revealed sequence variations in their coding regions. The relative expression levels of these two genes in Jing2416K were found to be significantly higher than those in Jing2416. Zm00001d023265 and Zm00001d023267 are thus potential RppM candidates.

7.
Aging (Albany NY) ; 12(11): 10642-10662, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32511103

RESUMO

DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.

8.
Nat Commun ; 11(1): 2220, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393777

RESUMO

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10-15) and replication (adjusted OR = 2.93, P = 2.22 × 10-3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10-22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.


Assuntos
Adenocarcinoma/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias Pulmonares/genética , Idoso , Alelos , Bases de Dados Genéticas , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Razão de Chances , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , RNA-Seq , Fatores de Risco
9.
Chest ; 158(2): 808-819, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32113923

RESUMO

BACKGROUND: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. RESEARCH QUESTION: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? STUDY DESIGN AND METHODS: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. RESULTS: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10-17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10-18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. INTERPRETATION: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.

10.
Gene ; 740: 144570, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32165298

RESUMO

Recent studies have found multiple single nucleotide variants (SNVs) associated with DNA damage. However, previous association analysis may ignore the potential interaction effects between SNVs. Therefore, we used an improved random forest (RF) analysis to identify the SNVs related to personal DNA damage in exon-focused genome-wide association study (GWAS). A total of 301 subjects from three independent centers (Zhuhai, Wuhan, and Tianjin) were retained for analysis. An improved RF procedure was used to systematically screen key SNVs associated with DNA damage. Furthermore, we used genetic risk score (GRS) and mediation analysis to investigate the integrative effect and potential mechanism of these genetic variants on DNA damage. Besides, gene set enrichment analysis was conducted to identify the pathways enriched by key SNVs using the Data-driven Expression Prioritized Integration for Complex Traits (DEPICT). Finally, a set of 24 SNVs with the lowest mean square errors (MSE) were identified by improved RF analysis. Both weighted and unweighted GRSs were associated with increased DNA damage levels (Pweight < 0.001 and Punweight < 0.001). Gene set enrichment analysis indicated that these loci were significantly enriched in several biological features associated with DNA damage. These findings suggested the role of SNVs in modifying DNA damage levels. It may be convincing that this improved RF analysis can effectively identify SNVs associated with DNA damage levels.


Assuntos
Dano ao DNA , Material Particulado/toxicidade , China , Dano ao DNA/genética , Dano ao DNA/fisiologia , Interpretação Estatística de Dados , Humanos , Material Particulado/sangue , Material Particulado/metabolismo , Polimorfismo de Nucleotídeo Único
11.
Microb Pathog ; 142: 104074, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105801

RESUMO

Plant endophytes are microbes that colonize plant internal tissues and are ubiquitously associated with plants. In this study, seven endophytic bacterial strains, 665L2, 725L2, 725R2, 92R2, 728R3, 728R4 and 2416T3, were isolated from seeds of five healthy maize varieties (Zea mays L.) and all identified as Bacillus velezensis by polyphasic taxonomy based on 16S rRNA and gyrA gene phylogenetic analysis. In addition, according to the genotyping results from random amplified polymorphic DNA (RAPD), 665L2, 725L2, 725R2 and 92R2 belonged to the same strain, while 728R3 and 2416T3 belonged to another strain. Pathogenic fungal strains 4, 5 and 6 were isolated from three diseased maize varieties (Zea mays L.), and they were identified as Talaromyces funiculosus, Penicillium oxalicum and Fusarium verticillioides, respectively, by polyphasic taxonomy based on morphological identification, ITS rDNA and bio-control gene phylogenetic analyses. Seven endophytic bacterial Bacillus velezensis strains had favourable antagonistic activity, and antagonistic testing was carried out against the three pathogenic strains, Talaromyces funiculosus 4, Penicillium oxalicum 5 and Fusarium verticillioides 6. Biological control lipopeptide antibiotic genes (bioA, bmyB, ituC, fenD, srfAA, srfAB, yngG and yndJ) were amplified using specific primers, and they were found in the seven endophytic bacterial Bacillus velezensis strains. This study provides a scientific basis for future research on the use of resistant endophytic bacterial resources to enhance crop production.

12.
3 Biotech ; 10(1): 27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31950006

RESUMO

This research aimed to investigate the composition and diversity of endophytic bacterial community in seeds of four hybrid maize and their parental lines, which was used to reveal the potential relationship and association of endophytic bacteria between maize genotypes and their genetic relevance. High-throughput sequencing (HTS) technology showed that a total of 1419 OTUs (46.6%) were parental lines unique and 1052 OTUs (34.5%) were hybrid varieties unique, with only 575 core OTUs revealed in all the samples. Most OTUs belonged to Proteobacteria. Enterobacter (23.2%), Shigella (21.2%), Pseudomonas (15.8%) and Achromobacter (10.1%) were the major genera; the bacterial community composition and diversity of endophytic bacteria were inconsistent among different seed genotypes. Based on principal component analysis (PCA), the results referred that the endophytic composition of hybrid sample showed obvious correlation with their female parental lines, and in 'Jingke968' and 'MC738' with the same female line the endophytic community was more similar than other hybrid samples. This was the first ever use of HTS technology for investigating the endophytic bacterial diversity and community structures in seeds of genetically related maize genotypes, it was shown that, there were core microbes shared among all genotypes of seed samples, and the female parental line was more significant to impact on the composition of their hybrid seeds than male parental line. This study would provide scientific clues for the future research on the vertical transmission of endophytes among maize generations.

13.
Genome Biol ; 21(1): 20, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980033

RESUMO

BACKGROUND: Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders. RESULTS: Hundreds of QTL for 23 agronomic traits are uncovered with 14 million high-quality SNPs and a high-resolution identity-by-descent map, which account for an average of 75% of the heritability for each trait. We find epistasis contributes to phenotypic variance widely. Integrative cross-population analysis and cross-omics mapping allow effective and rapid discovery of underlying genes, validated here with a case study on leaf width. CONCLUSIONS: Through the integration of experimental genetics and genomics, our study provides useful resources and gene mining strategies to explore complex quantitative traits.


Assuntos
Locos de Características Quantitativas , Zea mays/genética , Alelos , Epistasia Genética , Perfilação da Expressão Gênica , Genes de Plantas , Estudo de Associação Genômica Ampla , Genômica , Fenótipo , Polimorfismo de Nucleotídeo Único
14.
Mol Oncol ; 14(11): 2759-2774, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33448640

RESUMO

Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30-2.09, P = 4.52 × 10-5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87-1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking (37.49LUAD vs 54.79LUSC, P = 1.03 × 10-19) and included a higher proportion of current smokers than LUAD patients (28.24%LUAD vs 34.09%LUSC, P = 0.037). cg05293407TRIM27 was significantly associated with overall survival only in NSCLC patients with medium-high pack-year of smoking (HR = 1.58, 95% CI: 1.26-1.96, P = 5.25 × 10-5). We conclude that cg05293407TRIM27 methylation is a potential predictor of LUSC prognosis, and smoking intensity may impact on its prognostic value across the various types of NSCLC.

15.
BMC Bioinformatics ; 20(1): 711, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842743

RESUMO

BACKGROUND: High-throughput technologies have brought tremendous changes to biological domains, and the resulting high-dimensional data has also posed enormous challenges to computational science. A Bayesian network is a probabilistic graphical model represented by a directed acyclic graph, which provides concise semantics to describe the relationship between entities and has an independence assumption that is suitable for sparse omics data. Bayesian networks have been broadly used in biomedical research fields, including disease risk assessment and prognostic prediction. However, the inference and visualization of Bayesian networks are unfriendly to the users lacking programming skills. RESULTS: We developed an R/Shiny application, shinyBN, which is an online graphical user interface to facilitate the inference and visualization of Bayesian networks. shinyBN supports multiple types of input and provides flexible settings for network rendering and inference. For output, users can download network plots, prediction results and external validation results in publication-ready high-resolution figures. CONCLUSION: Our user-friendly application (shinyBN) provides users with an easy method for Bayesian network modeling, inference and visualization via mouse clicks. shinyBN can be used in the R environment or online and is compatible with three major operating systems, including Windows, Linux and Mac OS. shinyBN is deployed at https://jiajin.shinyapps.io/shinyBN/. Source codes and the manual are freely available at https://github.com/JiajinChen/shinyBN.


Assuntos
Teorema de Bayes , Redes Neurais de Computação , Software
16.
Aging (Albany NY) ; 11(16): 6312-6335, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434796

RESUMO

Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais , Neoplasias Pulmonares/metabolismo , Prognóstico , Adenocarcinoma de Pulmão/genética , Idoso , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
17.
Environ Health ; 18(1): 60, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262333

RESUMO

BACKGROUND: The link between use of solid biomass fuel (wood, charcoal, coal, dung, and crop residues) for cooking and/or heating and esophageal squamous cell carcinoma (ESCC) is inconclusive. OBJECTIVE: We systematically reviewed the literature and performed a meta-analysis to determine whether cooking fuel type influences esophageal squamous cell carcinoma. METHODS: We searched MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating cooking fuel and ESCC from 2000 until March 2019. We performed random effects meta-analysis stratified by the continent, World Bank's country income classifications and fuel type and calculated pooled odds ratios and 95% CIs for the risk of esophageal squamous cell carcinoma in biomass fuel users compared with non-users. RESULTS: Our analysis included 16 studies (all case-control) with 16,189 participants (5233 cases and 10,956 controls) that compared risk of ESCC among those using nonsolid fuels and biomass fuels. We found use of biomass fuel was associated with Esophageal squamous cell carcinoma with a pooled odds ratio (OR) 3.02 (95% CI 2.22, 4.11, heterogeneity (I2) = 79%). In sub-group analyses by continent, Africa (OR 3.35, 95%CI 2.34, 4.80, I2 = 73.4%) and Asia (OR 3.08, 95%CI 1.27, 7.43, I2 = 81.7%) had the highest odds of ESCC. Use of wood as fuel had the highest odds of 3.90, 95% CI 2.25, 6.77, I2 = 63.5%). No significant publication bias was detected. CONCLUSIONS: Biomass fuel is associated with increased risk of Esophageal squamous cell carcinoma. Biomass fuel status should be considered in the risk assessment for Esophageal squamous cell carcinoma.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Biomassa , Culinária , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Calefação , Carvão Vegetal/efeitos adversos , Carvão Mineral/efeitos adversos , Neoplasias Esofágicas/induzido quimicamente , Carcinoma de Células Escamosas do Esôfago/induzido quimicamente , Fezes , Humanos , Fatores de Risco , Madeira/efeitos adversos
18.
Sci Rep ; 9(1): 8183, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160669

RESUMO

The maize stalk is an important mechanical supporting tissue. The stalk fracture resistance is closely related to lodging resistance, and thus the yield. In this study, we showed that the basal zone (BZ) was more fragile than the middle zone (MZ) of the stalk internode before tasseling. In order to clarify the relationship between the different zones and fragile resistance between the internodes, we systematically analyzed the phenotypic, metabolomic and transcriptomic differences. The results indicated that the BZ zone had lower stalk strength, which corresponded to the results of less lignin, cellulose and hemicellulose than that of the MZ. The 27 highly enriched metabolites and 4430 highly expressed genes in the BZ mainly participated in pentose phosphate, and in ribosome and sterol synthesis pathways, respectively. In addition, the BZ had higher vascular bundles density but smaller size compared with the MZ. By contrast, the 28 highly enriched known metabolites and 4438 highly expressed genes in the MZ were mainly involved in lignin synthesis, and secondary metabolites synthesis, respectively, especially the phenylpropanoid synthesis. The results provide a deeper understanding of the relationship between development and fracture differences in stalk, and may facilitate the improvement of field management practice to reduce lodging.


Assuntos
Celulose/genética , Proteínas de Plantas/genética , Zea mays/genética , Parede Celular/genética , Celulose/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Lignina/genética , Fenótipo , Locos de Características Quantitativas/genética , Zea mays/metabolismo
19.
Mol Oncol ; 13(5): 1235-1248, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30924596

RESUMO

Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome-wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two-stage study design to identify DNA methylation-smoking cessation interactions that affect overall survival for early-stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology-stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation-smoking cessation interaction terms. Interactions with false discovery rate-q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology-specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510SIPA 1L3 ) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR)interaction  = 1.12; 95% confidence interval (CI): 1.07-1.16; P = 4.30 × 10-7 ]. Further, the effect of smoking cessation on early-stage LUAD survival varied across patients with different methylation levels of cg02268510SIPA 1L3 . Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34-0.82; P = 4.61 × 10-3 ) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86-1.70; P = 0.266) of cg02268510SIPA 1L3 . Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA 1L3 and smoking cessation (HRinteraction  = 2.1835; 95% CI: 1.27-3.74; P = 4.46 × 10-3 ). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510SIPA 1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting.


Assuntos
Metilação de DNA , DNA de Neoplasias , Proteínas Ativadoras de GTPase , Neoplasias Pulmonares , Proteínas de Neoplasias , Abandono do Hábito de Fumar , Fumar , Adenocarcinoma de Pulmão , Idoso , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Intervalo Livre de Doença , Epigenômica , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fumar/genética , Fumar/metabolismo , Fumar/mortalidade , Fumar/patologia , Taxa de Sobrevida
20.
Sci Rep ; 9(1): 3458, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837510

RESUMO

Plant height (PH) is a key factor in maize (Zea mays L.) yield, biomass, and plant architecture. We investigated the PH of diverse maize inbred lines (117 temperate lines, 135 tropical lines) at four growth stages using unmanned aerial vehicle high-throughput phenotypic platforms (UAV-HTPPs). We extracted PH data using an automated pipeline based on crop surface models and orthomosaic model. The correlation between UAV and manually measured PH data reached 0.95. Under temperate field conditions, temperate maize lines grew faster than tropical maize lines at early growth stages, but tropical lines grew faster at later growth stages and ultimately became taller than temperate lines. A genome-wide association study identified 68 unique quantitative trait loci (QTLs) for seven PH-related traits, and 35% of the QTLs coincided with those previously reported to control PH. Generally, different QTLs controlled PH at different growth stages, but eight QTLs simultaneously controlled PH and growth rate at multiple growth stages. Based on gene annotations and expression profiles, we identified candidate genes controlling PH. The PH data collected by the UAV-HTPPs were credible and the genetic mapping power was high. Therefore, UAV-HTPPs have great potential for use in studies on PH.


Assuntos
Estudos de Associação Genética , Locos de Características Quantitativas , Característica Quantitativa Herdável , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/métodos , Zea mays/genética , Mapeamento Cromossômico , Meio Ambiente , Heterogeneidade Genética , Fenótipo
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