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  1. AU="Xingyi Guo"
  2. AU="Gang Lin"
  3. AU="Oka, T"
  4. AU="Frank-Pearce, Summer G"
  5. AU="Hairi Li"
  6. AU="Park, SungHee"
  7. AU="Pascual-Carreras, Eudald"
  8. AU=Joffe Ari R
  9. AU="Buccafurri, Francesco"
  10. AU="Naomi H. Philip"
  11. AU="P. Naina"
  12. AU="Sigal, Leonard H"
  13. AU="Xu, T" AU="Xu, T"
  14. AU="Mazlout, Adam"
  15. AU="Novak, Cheryl B"
  16. AU="Ren, Zhongmin"
  17. AU="Nadhira Houhou-Fidouh"
  18. AU="Seiffert, Jacqui"
  19. AU=Zhang Zizhen
  20. AU="Bhupender Singh Negi"

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  1. Artikel ; Online: Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

    Xingyi Guo / Zhishan Chen / Yumin Xia / Weiqiang Lin / Hongzhi Li

    Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-

    2020  Band 9

    Abstract: Abstract Background The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 ( ...

    Abstract Abstract Background The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein–protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program. Results Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian. Conclusions We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.
    Schlagwörter COVID-19 ; ACE2 ; SARS-CoV-2 ; S-protein ; Missense ; Medicine ; R ; covid19
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2020-08-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility

    Wanqing Wen / Zhishan Chen / Jiandong Bao / Quan Long / Xiao-ou Shu / Wei Zheng / Xingyi Guo

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 12

    Abstract: The identification of transcription factors (TFs) whose binding sites are affected by risk genetic variants remains crucial. Here, the authors develop a statistical framework to analyse ChIP-seq and GWAS data, identify 22 breast cancer risk-associated ... ...

    Abstract The identification of transcription factors (TFs) whose binding sites are affected by risk genetic variants remains crucial. Here, the authors develop a statistical framework to analyse ChIP-seq and GWAS data, identify 22 breast cancer risk-associated TFs and a core TF-transcriptional network for FOXA1 and co-factors.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-09-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Association between lipid peroxidation biomarkers and microRNA expression profiles

    Yingya Zhao / Marina S. Nogueira / Ginger L. Milne / Xingyi Guo / Hui Cai / Qing Lan / Nathaniel Rothman / Qiuyin Cai / Yu-Tang Gao / Qingxia Chen / Xiao-Ou Shu / Gong Yang

    Redox Biology, Vol 58, Iss , Pp 102531- (2022)

    2022  

    Abstract: Background: In-vitro and animal studies demonstrate that epigenetic regulation may play an important role in lipid peroxidation. No human study to date has directly evaluated microRNAs (miRNAs), as epigenetic modulators, in relation to systemic levels of ...

    Abstract Background: In-vitro and animal studies demonstrate that epigenetic regulation may play an important role in lipid peroxidation. No human study to date has directly evaluated microRNAs (miRNAs), as epigenetic modulators, in relation to systemic levels of lipid peroxidation. Objectives: To evaluate associations between systemic levels of lipid peroxidation and miRNA expression profiles in women. Methods: Included in the analysis were 92 women aged 40–70 years, a subset of the Shanghai Women’s Health Study (SWHS). Lipid peroxidation was assessed by urinary markers F2-isoprostanes (F2-IsoPs), the products of free radical-catalyzed peroxidation of arachidonic acid, and its major metabolite after β-oxidation, 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M), with GC/NICI-MS assays. Expression levels of 798 miRNAs were quantified in peripheral plasma with NanoString nCounter assays. A multivariable linear regression model was used to examine the association between lipid peroxidation and miRNA expression. Results: After adjusting for potential confounders, 29 miRNAs and 213 miRNAs were associated with F2-IsoPs and F2-IsoP-M, respectively. When further controlling for multiple comparisons, none of these nominally significant associations with F2-IsoPs was retained, whereas 71 of 213 miRNAs associated with F2-IsoP-M remained. The predicted targets of the F2-IsoP-M associated miRNAs were enriched for several lipid peroxidation-related processes such as PI3K/AKT, MAPK, FOXO and HIF-1 signaling pathways. Moreover, 10 miRNAs (miR-93-5p, miR-761, miR-301b-3p, miR-497-5p, miR-141-3p, miR-186-5p, miR-126-3p, miR-200b-3p, miR-520d-3p, and miR-363-3p) exhibited functional interactions with 50 unique mRNAs targets involved in the regulation of β-oxidation. Conclusions: To our knowledge, this study, for the first time, provides human data suggesting that miRNA expression may be linked to lipid peroxidation products and their metabolism.
    Schlagwörter Biomarker ; Oxidative stress ; Lipid peroxidation ; Isoprostanes ; microRNA ; β-oxidation ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 500
    Sprache Englisch
    Erscheinungsdatum 2022-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
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  4. Artikel ; Online: De novo assembly and analysis of the Artemisia argyi transcriptome and identification of genes involved in terpenoid biosynthesis

    Miaomiao Liu / Jinhang Zhu / Shengbing Wu / Chenkai Wang / Xingyi Guo / Jiawen Wu / Meiqi Zhou

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Band 10

    Abstract: Abstract Artemisia argyi Lev. et Vant. (A. argyi) is widely utilized for moxibustion in Chinese medicine, and the mechanism underlying terpenoid biosynthesis in its leaves is suggested to play an important role in its medicinal use. However, the A. argyi ...

    Abstract Abstract Artemisia argyi Lev. et Vant. (A. argyi) is widely utilized for moxibustion in Chinese medicine, and the mechanism underlying terpenoid biosynthesis in its leaves is suggested to play an important role in its medicinal use. However, the A. argyi transcriptome has not been sequenced. Herein, we performed RNA sequencing for A. argyi leaf, root and stem tissues to identify as many as possible of the transcribed genes. In total, 99,807 unigenes were assembled by analysing the expression profiles generated from the three tissue types, and 67,446 of those unigenes were annotated in public databases. We further performed differential gene expression analysis to compare leaf tissue with the other two tissue types and identified numerous genes that were specifically expressed or up-regulated in leaf tissue. Specifically, we identified multiple genes encoding significant enzymes or transcription factors related to terpenoid synthesis. This study serves as a valuable resource for transcriptome information, as many transcribed genes related to terpenoid biosynthesis were identified in the A. argyi transcriptome, providing a functional genomic basis for additional studies on molecular mechanisms underlying the medicinal use of A. argyi.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 580
    Sprache Englisch
    Erscheinungsdatum 2018-04-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
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  5. Artikel ; Online: Integrative genomic analyses of APOBEC-mutational signature, expression and germline deletion of APOBEC3 genes, and immunogenicity in multiple cancer types

    Zhishan Chen / Wanqing Wen / Jiandong Bao / Krystle L. Kuhs / Qiuyin Cai / Jirong Long / Xiao-ou Shu / Wei Zheng / Xingyi Guo

    BMC Medical Genomics, Vol 12, Iss 1, Pp 1-

    2019  Band 13

    Abstract: Abstract Background Although APOBEC-mutational signature is found in tumor tissues of multiple cancers, how a common germline APOBEC3A/B deletion affects the mutational signature remains unclear. Methods Using data from 10 cancer types generated as part ... ...

    Abstract Abstract Background Although APOBEC-mutational signature is found in tumor tissues of multiple cancers, how a common germline APOBEC3A/B deletion affects the mutational signature remains unclear. Methods Using data from 10 cancer types generated as part of TCGA, we performed integrative genomic and association analyses to assess inter-relationship of expressions for isoforms APOBEC3A and APOBEC3B, APOBEC-mutational signature, germline APOBEC3A/B deletions, neoantigen loads, and tumor infiltration lymphocytes (TILs). Results We found that expression level of the isoform uc011aoc transcribed from the APOBEC3A/B chimera was associated with a greater burden of APOBEC-mutational signature only in breast cancer, while germline APOBEC3A/B deletion led to an increased expression level of uc011aoc in multiple cancer types. Furthermore, we found that the deletion was associated with elevated APOBEC-mutational signature, neoantigen loads and relative composition of T cells (CD8+) in TILs only in breast cancer. Additionally, we also found that APOBEC-mutational signature significantly contributed to neoantigen loads and certain immune cell abundances in TILs across cancer types. Conclusions These findings reveal new insights into understanding the genetic, biological and immunological mechanisms through which APOBEC genes may be involved in carcinogenesis, and provide potential genetic biomarker for the development of disease prevention and cancer immunotherapy.
    Schlagwörter Pan-cancer ; APOBEC ; Gene expression ; Isoforms ; APOBEC-signature mutations ; Germline APOBEC3A/B deletion ; Internal medicine ; RC31-1245 ; Genetics ; QH426-470
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2019-09-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Regional Differences in Epidemiological and Clinical Characteristics, Treatment, and Clinical Outcomes of COVID-19 in Wuhan and Remote Areas of Hubei Province

    Honggang Ren / Xingyi Guo / Antonio Palazón-Bru / Pengcheng Yang / Nan Huo / Runsheng Wang / Yu Sun / Qinyong Hu / Hua Yang / Guogang Xu

    Frontiers in Medicine, Vol

    2021  Band 8

    Abstract: Background: The Coronavirus disease 2019 (COVID-19) pandemic has been a major threat to global health. Regional differences in epidemiological and clinical characteristics, treatment and outcomes of patients have not yet been investigated. This study was ...

    Abstract Background: The Coronavirus disease 2019 (COVID-19) pandemic has been a major threat to global health. Regional differences in epidemiological and clinical characteristics, treatment and outcomes of patients have not yet been investigated. This study was conducted to investigate these differences amongCOVID-19 patients in Hubei Province, China.Methods: This retrospective cross-sectional study analyzed data on 289 COVID-19 patients from designated hospitals in three regions:Urban (Wuhan Union West Hospital), Suburban areas of Wuhan (Hannan Hospital) and Enshi city, between February 8 and 20, 2020. The final date of follow-up was December 14th, 2020. The outcomes were case fatality rate and epidemiological and clinical data.Results: Urban Wuhan experienced a significantly higher case fatality rate (21.5%) than suburban Wuhan (5.23%) and rural area of Enshi (3.51%). Urban Wuhan had a higher proportion of patients on mechanical ventilation (24.05%) than suburban Wuhan (0%) and rural Enshi (3.57%). Treatment with glucocorticoids was equivalent in urban and suburban Wuhan (46.84 and 45.75%, respectively) and higher than Enshi (25.00%). Urban Wuhan had a higher proportion of patients with abnormal tests including liver function and serum electrolytes and a higher rate of pneumonia (p < 0.01 for all). Urban Wuhan also had a higher incidence of respiratory failure, heart disease, liver disease and shock, compared with the other two regions (all p < 0.05).Conclusions: Our findings revealed that there are regional differences in COVID-19. These findings provide novel insights into the distribution of appropriate resources for the prevention, control and treatment of COVID-19 for the global community.
    Schlagwörter SARS-CoV-2 ; COVID-19 ; regional differences ; mortality ; clinical characteristics ; Medicine (General) ; R5-920
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-07-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
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  7. Artikel ; Online: Characterization of human pseudogene-derived non-coding RNAs for functional potential.

    Xingyi Guo / Mingyan Lin / Shira Rockowitz / Herbert M Lachman / Deyou Zheng

    PLoS ONE, Vol 9, Iss 4, p e

    2014  Band 93972

    Abstract: Thousands of pseudogenes exist in the human genome and many are transcribed, but their functional potential remains elusive and understudied. To explore these issues systematically, we first developed a computational pipeline to identify transcribed ... ...

    Abstract Thousands of pseudogenes exist in the human genome and many are transcribed, but their functional potential remains elusive and understudied. To explore these issues systematically, we first developed a computational pipeline to identify transcribed pseudogenes from RNA-Seq data. Applying the pipeline to datasets from 16 distinct normal human tissues identified ∼ 3,000 pseudogenes that could produce non-coding RNAs in a manner of low abundance but high tissue specificity under normal physiological conditions. Cross-tissue comparison revealed that the transcriptional profiles of pseudogenes and their parent genes showed mostly positive correlations, suggesting that pseudogene transcription could have a positive effect on the expression of their parent genes, perhaps by functioning as competing endogenous RNAs (ceRNAs), as previously suggested and demonstrated with the PTEN pseudogene, PTENP1. Our analysis of the ENCODE project data also found many transcriptionally active pseudogenes in the GM12878 and K562 cell lines; moreover, it showed that many human pseudogenes produced small RNAs (sRNAs) and some pseudogene-derived sRNAs, especially those from antisense strands, exhibited evidence of interfering with gene expression. Further integrated analysis of transcriptomics and epigenomics data, however, demonstrated that trimethylation of histone 3 at lysine 9 (H3K9me3), a posttranslational modification typically associated with gene repression and heterochromatin, was enriched at many transcribed pseudogenes in a transcription-level dependent manner in the two cell lines. The H3K9me3 enrichment was more prominent in pseudogenes that produced sRNAs at pseudogene loci and their adjacent regions, an observation further supported by the co-enrichment of SETDB1 (a H3K9 methyltransferase), suggesting that pseudogene sRNAs may have a role in regional chromatin repression. Taken together, our comprehensive and systematic characterization of pseudogene transcription uncovers a complex picture of how pseudogene ncRNAs could ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570 ; 572
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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  8. Artikel ; Online: Small RNAs originated from pseudogenes

    Xingyi Guo / Zhaolei Zhang / Mark B Gerstein / Deyou Zheng

    PLoS Computational Biology, Vol 5, Iss 7, p e

    cis- or trans-acting?

    2009  Band 1000449

    Abstract: Pseudogenes are significant components of eukaryotic genomes, and some have acquired novel regulatory roles. To date, no study has characterized rice pseudogenes systematically or addressed their impact on the structure and function of the rice genome. ... ...

    Abstract Pseudogenes are significant components of eukaryotic genomes, and some have acquired novel regulatory roles. To date, no study has characterized rice pseudogenes systematically or addressed their impact on the structure and function of the rice genome. In this genome-wide study, we have identified 11,956 non-transposon-related rice pseudogenes, most of which are from gene duplications. About 12% of the rice protein-coding genes, half of which are in singleton families, have a pseudogene paralog. Interestingly, we found that 145 of these pseudogenes potentially gave rise to antisense small RNAs after examining approximately 1.5 million small RNAs from developing rice grains. The majority (>50%) of these antisense RNAs are 24-nucleotides long, a feature often seen in plant repeat-associated small interfering RNAs (siRNAs) produced by RNA-dependent RNA polymerase (RDR2) and Dicer-like protein 3 (DCL3), suggesting that some pseudogene-derived siRNAs may be implicated in repressing pseudogene transcription (i.e., cis-acting). Multiple lines of evidence, however, indicate that small RNAs from rice pseudogenes might also function as natural antisense siRNAs either by interacting with the complementary sense RNAs from functional parental genes (38 cases) or by forming double-strand RNAs with transcripts of adjacent paralogous pseudogenes (2 cases) (i.e., trans-acting). Further examinations of five additional small RNA libraries revealed that pseudogene-derived antisense siRNAs could be produced in specific rice developmental stages or physiological growth conditions, suggesting their potentially important roles in normal rice development. In summary, our results show that pseudogenes derived from protein-coding genes are prevalent in the rice genome, and a subset of them are strong candidates for producing small RNAs with novel regulatory roles. Our findings suggest that pseudogenes of exapted functions may be a phenomenon ubiquitous in eukaryotic organisms.
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2009-07-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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  9. Artikel ; Online: An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

    Lang Wu / Yaohua Yang / Xingyi Guo / Xiao-Ou Shu / Qiuyin Cai / Xiang Shu / Bingshan Li / Ran Tao / Chong Wu / Jason B. Nikas / Yanfa Sun / Jingjing Zhu / Monique J. Roobol / Graham G. Giles / Hermann Brenner / Esther M. John / Judith Clements / Eli Marie Grindedal / Jong Y. Park /
    Janet L. Stanford / Zsofia Kote-Jarai / Christopher A. Haiman / Rosalind A. Eeles / Wei Zheng / Jirong Long / The PRACTICAL consortium / CRUK Consortium / BPC3 Consortium / CAPS Consortium / PEGASUS Consortium

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Band 11

    Abstract: Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG ... ...

    Abstract Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2020-08-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

    Lang Wu / Yaohua Yang / Xingyi Guo / Xiao-Ou Shu / Qiuyin Cai / Xiang Shu / Bingshan Li / Ran Tao / Chong Wu / Jason B. Nikas / Yanfa Sun / Jingjing Zhu / Monique J. Roobol / Graham G. Giles / Hermann Brenner / Esther M. John / Judith Clements / Eli Marie Grindedal / Jong Y. Park /
    Janet L. Stanford / Zsofia Kote-Jarai / Christopher A. Haiman / Rosalind A. Eeles / Wei Zheng / Jirong Long / The PRACTICAL consortium / CRUK Consortium / BPC3 Consortium / CAPS Consortium / PEGASUS Consortium

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Band 11

    Abstract: Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG ... ...

    Abstract Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2020-08-01T00:00:00Z
    Verlag Nature Portfolio
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