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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 19 ( 2015-05-12)
    Abstract: Maize is a major crop and a model plant for studying C4 photosynthesis and leaf development. However, a genomewide regulatory network of leaf development is not yet available. This knowledge is useful for developing C3 crops to perform C4 photosynthesis for enhanced yields. Here, using 22 transcriptomes of developing maize leaves from dry seeds to 192 h post imbibition, we studied gene up- and down-regulation and functional transition during leaf development and inferred sets of strongly coexpressed genes. More significantly, we developed a method to predict transcription factor binding sites (TFBSs) and their cognate transcription factors (TFs) using genomic sequence and transcriptomic data. The method requires not only evolutionary conservation of candidate TFBSs and sets of strongly coexpressed genes but also that the genes in a gene set share the same Gene Ontology term so that they are involved in the same biological function. In addition, we developed another method to predict maize TF–TFBS pairs using known TF–TFBS pairs in Arabidopsis or rice. From these efforts, we predicted 1,340 novel TFBSs and 253 new TF–TFBS pairs in the maize genome, far exceeding the 30 TF–TFBS pairs currently known in maize. In most cases studied by both methods, the two methods gave similar predictions. In vitro tests of 12 predicted TF–TFBS interactions showed that our methods perform well. Our study has significantly expanded our knowledge on the regulatory network involved in maize leaf development.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 10 ( 2013-03-05), p. 3979-3984
    Abstract: Our anatomical analysis revealed that a dry maize seed contains four to five embryonic leaves at different developmental stages. Rudimentary kranz structure (KS) is apparent in the first leaf with a substantial density, but its density decreases toward younger leaves. Upon imbibition, leaf expansion occurs rapidly with new KSs initiated from the palisade-like ground meristem cells in the middle of the leaf. In parallel to the anatomical analysis, we obtained the time course transcriptomes for the embryonic leaves in dry and imbibed seeds every 6 h up to hour 72. Over this time course, the embryonic leaves exhibit transcripts of 30,255 genes at a level that can be regarded as “expressed.” In dry seeds, ∼25,500 genes are expressed, showing functional enrichment in transcription, RNA processing, protein synthesis, primary metabolic pathways, and calcium transport. During the 72-h time course, ∼13,900 genes, including 590 transcription factor genes, are differentially expressed. Indeed, by 30 h postimbibition, ∼2,200 genes expressed in dry seeds are already down-regulated, and ∼2,000 are up-regulated. Moreover, the top 1% expressed genes at 54 h or later are very different from those before 30 h, reflecting important developmental and physiological transitions. Interestingly, clusters of genes involved in hormone metabolism, signaling, and responses are differentially expressed at various time points and TF gene expression is also modular and stage specific. Our dataset provides an opportunity for hypothesizing the timing of regulatory actions, particularly in the context of KS development.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2014
    In:  BMC Genomics Vol. 15, No. 1 ( 2014), p. 818-
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2014), p. 818-
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
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    SSG: 12
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-05)
    Abstract: Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35–79 who had two or more health examinations during 1996–2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 5
    In: Tumor Biology, IOS Press, Vol. 39, No. 6 ( 2017-06), p. 101042831770557-
    Type of Medium: Online Resource
    ISSN: 1010-4283 , 1423-0380
    Language: English
    Publisher: IOS Press
    Publication Date: 2017
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    detail.hit.zdb_id: 1483579-4
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  • 6
    In: Clinical Immunology, Elsevier BV, ( 2024-1), p. 109897-
    Type of Medium: Online Resource
    ISSN: 1521-6616
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1462862-4
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  • 7
    In: Cells, MDPI AG, Vol. 11, No. 7 ( 2022-04-05), p. 1231-
    Abstract: RNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate dehydrogenase mutated (IDH-MUT) gliomas from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas (CGGA). We showed that editing change during glioma progression was another layer of molecular alterations and that editing profiles predicted the prognosis of glioblastoma and IDH-MUT gliomas in a sex-dependent manner. Hyper-editing was associated with poor survival in females but better survival in males. Moreover, noncoding editing events impacted mRNA abundance of the host genes. Genes associated with inflammatory response (e.g., EIF2AK2, a key mediator of innate immunity) and fatty acid oxidation (e.g., acyl-CoA oxidase 1, the rate-limiting enzyme in fatty acid β-oxidation) were editing-regulated and associated with glioma progression. The above findings were further validated in CGGA samples. Establishment of the prognostic and regulatory roles of RNA editing in glioma holds promise for developing editing-based therapeutic strategies against glioma progression. Furthermore, sexual dimorphism at the epitranscriptional level highlights the importance of developing sex-specific treatments for glioma.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 8
    Online Resource
    Online Resource
    BMJ ; 2021
    In:  Journal of Epidemiology and Community Health Vol. 75, No. 12 ( 2021-12), p. 1215-1221
    In: Journal of Epidemiology and Community Health, BMJ, Vol. 75, No. 12 ( 2021-12), p. 1215-1221
    Abstract: Increases in physical activity (PA) and weight have opposite effects on the risk of non-alcoholic fatty liver disease (NAFLD), but their joint effect remains unknown. We examined the dose-effect of PA increase for NAFLD prevention and the amount of PA increase required to offset the deleterious effect of weight gain. Methods We analysed 47 058 participants who were extracted from the Taiwan MJ cohort, aged 20–50 years, without NAFLD at baseline, and followed at 1–5 years between 1997 and 2016. The outcome was incident NAFLD, diagnosed by ultrasonography. PA was measured by metabolic equivalents (METs) and duration (hour/week). We used flexible parametric survival models to estimate the HRs of annual change in PA and body mass index (BMI), controlling for their interaction and baseline covariates. Results During 138 646 person-years of follow-up, 12 836 participants (40.6% men and 20.1% women) developed incident NAFLD. The HR (95% CI) of annual PA increase of 1 MET-hour/week was 0.88 (0.85–0.92) after controlling for weight change. Moreover, 28 min/week of moderate-intensity PA could neutralise NAFLD risk elevated by annual BMI increase of 0.1 kg/m 2 at the end of year 3. We also observed an extra 35% risk reduction when PA increase (1 MET-hour/week) and weight loss (0.1 kg/m 2 ) occurred simultaneously. Conclusions Annual PA increase of 1 MET-hour/week was associated with a 12% lower NAFLD risk. PA increase can counteract the harmful effect of weight gain and there is a synergistic effect from PA increase and weight loss.
    Type of Medium: Online Resource
    ISSN: 0143-005X , 1470-2738
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2015405-7
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2019
    In:  BMC Bioinformatics Vol. 20, No. S19 ( 2019-12)
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 20, No. S19 ( 2019-12)
    Abstract: Accurate classification of diffuse gliomas, the most common tumors of the central nervous system in adults, is important for appropriate treatment. However, detection of isocitrate dehydrogenase ( IDH ) mutation and chromosome1p/19q codeletion, biomarkers to classify gliomas, is time- and cost-intensive and diagnostic discordance remains an issue. Adenosine to inosine (A-to-I) RNA editing has emerged as a novel cancer prognostic marker, but its value for glioma classification remains largely unexplored. We aim to (1) unravel the relationship between RNA editing and IDH mutation and 1p/19q codeletion and (2) predict IDH mutation and 1p/19q codeletion status using machine learning algorithms. Results By characterizing genome-wide A-to-I RNA editing signatures of 638 gliomas, we found that tumors without IDH mutation exhibited higher total editing level compared with those carrying it (Kolmogorov-Smirnov test, p   〈  0.0001). When tumor grade was considered, however, only grade IV tumors without IDH mutation exhibited higher total editing level. According to 10-fold cross-validation, support vector machines (SVM) outperformed random forest and AdaBoost (DeLong test, p   〈  0.05). The area under the receiver operating characteristic curve (AUC) of SVM in predicting IDH mutation and 1p/19q codeletion were 0.989 and 0.990, respectively. After performing feature selection, AUCs of SVM and AdaBoost in predicting IDH mutation were higher than that of random forest (0.985 and 0.983 vs. 0.977; DeLong test, p   〈  0.05), but AUCs of the three algorithms in predicting 1p/19q codeletion were similar (0.976–0.982). Furthermore, 67% of the six continuously misclassified samples by our 1p/19q codeletion prediction models were misclassifications in the original labelling after inspection of 1p/19q status and/or pathology report, highlighting the accuracy and clinical utility of our models. Conclusions The study represents the first genome-wide analysis of glioma editome and identifies RNA editing as a novel prognostic biomarker for glioma. Our prediction models provide standardized, accurate, reproducible and objective classification of gliomas. Our models are not only useful in clinical decision-making, but also able to identify editing events that have the potential to serve as biomarkers and therapeutic targets in glioma management and treatment.
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  Neuro-Oncology Vol. 25, No. Supplement_3 ( 2023-09-16), p. iii7-iii7
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_3 ( 2023-09-16), p. iii7-iii7
    Abstract: Glioblastoma (GBM) remains incurable because of the high level of intratumor heterogeneity and the poor understanding of its complex genetics. We recently identified adenosine to inosine (A-to-I) RNA editing as a sex- specific prognostic factor in GBM. However, the underlying mechanism remains unclear. We sought to identify RNA editing-associated molecular effectors and assess their prognosis potential. METHOD We analyzed RNA-Seq data of 196 primary IDH wild-type GBMs from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts. Genome-wide A-to-I RNA editing events were characterized and GBM tumours were split into two subtypes based on RNA editing signatures (high- and low-editing). Differential expression and tumour microenvironment analyses between the two subtypes were performed to identify molecular effectors. Survival impact of these effectors was determined using Cox proportional hazards model. RESULTS Genes more highly expressed in the high-editing subtype were enriched in immune-related pathways, while those more highly expressed in the low-editing subtype were enriched in cell proliferation and stemness path- ways. Consistent with differential expression analysis, high-editing GBMs exhibited higher infiltration levels of macrophages, monocytes and dendritic cells. Intriguingly, increased cell proliferation and elevated infiltration of dendritic cells were associated with poorer survival in men only, whereas enhanced CSF1 (colony stimulating factor 1) response and elevated infiltration of monocytes and Th1 cells conferred poorer survival outcomes in women only. CONCLUSIONS Our study suggests sex-specific impact of A-to-I RNA editing in the pathogenesis of glioblastoma, highlighting the importance of developing sex-specific treatments and opening a new avenue for the design of novel therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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