scholarly journals Whole genome methylation array reveals the down-regulation of IGFBP6 and SATB2 by HIV-1

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yinfeng Zhang ◽  
Sai-Kam Li ◽  
Kevin Yi Yang ◽  
Minghua Liu ◽  
Nelson Lee ◽  
...  
Keyword(s):  
Whole Genome ◽  
Down Regulation ◽  
Methylation Array ◽  
Genome Methylation ◽  
Hiv 1

Genome-wide methylation profiling to identify potential epigenetic biomarkers associated with response to sunitinib in metastatic renal cell cancer (mRCC) patients (pts).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4566-4566 ◽  
Author(s):  
Jenny J. Kim ◽  
Mariette Labots ◽  
Luigi Marchionni ◽  
Shahnaz Begum ◽  
Gerrit A. Meijer ◽  
...  
Keyword(s):  
Empirical Bayes ◽  
Clear Cell ◽  
Cell Cancer ◽  
Significant Heterogeneity ◽  
Whole Genome ◽  
Methylation Array ◽  
Cell Subtype ◽  
Epigenetic Biomarkers ◽  
Genome Methylation ◽  
Differentially Methylated Genes

4566 Background: There exists a significant heterogeneity in the clinical response to sunitinib among pts treated for mRCC and, thus, a biomarker which would predict pts’ response up front would be an invaluable tool in the clinical management of these pts. In this regard, whole genome methylation array was performed between 2 extreme groups: sunitinib responders (RES) and non-responders (NRES) to identify differentially methylated genes between these subsets of pts. Methods: mRCC pts who received sunitinib therapy with available frozen nephrectomy tissues (stored at -80°C) and clinical data were identified. RES were identified as pts with progression free survival (PFS) of > or =11 months (mos) and NRES as those with PFS < or = 3 mos. After DNA extraction and quality assurance according to standard protocol, whole genome methylation array was performed using Infinium Humanmethylation450 BeadChip Kit - Illumina. Data normalization was achieved by subset-quantile within array normalization (PMID: 22703947). Differentially methylated regions were identified using logit transformed Beta values, using an F-test after shrinking variance via empirical Bayes (PMID: 21118553). Results: Total of 13 pts who received sunitinib therapy with available frozen nephrectomy tissues were identified. Of the 13, 5 pts qualified for each RES and NRES cohort as described in methods section. All pts in RES group had clear cell subtype. Two pts of the NRES group were of non-clear cell subtype. The QC plots showed that all arrays were successful. For RES vs. NRES, one genomic location, DENND2D, was significantly hypermethylated in the RES group with a false discovery rate (FDR) of <10%. DENND2D has been identified as a tumor suppressor-like gene in non-small cell lung cancer and melanoma cell lines in the recent past. Conclusions: In this study, DENND2D was significantly hypermethylated in sunitinib RES compared to NRES among mRCC pts. Data analysis with a less stringent FDR is also being pursued. Technical validation as well as clinical validation of DENND2D utilizing a larger pt cohort are ongoing.

scholarly journals Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Rada Staneva ◽  
Blaga Rukova ◽  
Savina Hadjidekova ◽  
Desislava Nesheva ◽  
Olga Antonova ◽  
...  
Keyword(s):  
Balkan Endemic Nephropathy ◽  
Whole Genome ◽  
Array Analysis ◽  
Methylation Array ◽  
Genome Methylation ◽  
Endemic Nephropathy

scholarly journals Whole genome methylation analysis of non-dysplastic Barretts oesophagus that progresses to invasive cancer

2017 ◽  
Author(s):  
MP Dilworth ◽  
T Nieto ◽  
JD Stockton ◽  
C Whalley ◽  
L Tee ◽  
...  
Keyword(s):  
Barrett’S Oesophagus ◽  
Surveillance Program ◽  
Whole Genome ◽  
Invasive Adenocarcinoma ◽  
Methylation Array ◽  
Bisulfite Pyrosequencing ◽  
Barrett's Oesophagus ◽  
Global Trend ◽  
Wilcoxon Rank Sum Test ◽  
Genome Methylation

ABSTRACTObjectiveTo investigate differences in methylation between patients with non-dysplastic Barretts’ oesophagus who progress to invasive adenocarcinoma and those that do not.DesignA whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with non-dysplastic Barrett’s Oesophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencingResultsIn total, 12 patients with “progressive” vs. 12 with “non-progressive” non-dysplastic Barrett’s oesophagus were analysed via methylation array. Fourty-four methylation markers were identified that may be able to discriminate between non-dysplastic Barrett’s Oesophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumour supressorOR3A4(probe cg09890332) validated in a separate cohort of samples (median methylation in progressors = 67.8% vs. 96.7% in non-progressors,p=0.0001, z = 3.85, Wilcoxon rank sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the two groups, but a global trend towards hypomethylation in the progressor group was observed.ConclusionHypomethylation ofOR3A4has the ability to risk stratify the patient with non-dysplastic Barrett’s Oesophagus and may form the basis of a future surveillance program.

Molecular and genetic characterization of natural variants of HIV-1 Nef gene from North India and its functional implication in down-regulation of MHC-I and CD-4

2020 ◽  
Vol 18 ◽  
Author(s):  
J. Singh ◽  
L. Ronsard ◽  
M. Pandey ◽  
R. Kapoor ◽  
V.G. Ramachandran ◽  
...  
Keyword(s):  
Biological Activities ◽  
Sequence Similarity ◽  
Eukaryotic Expression ◽  
North India ◽  
Cell Surface Expression ◽  
Functional Domains ◽  
Wild Type ◽  
Down Regulation ◽  
Subtype B ◽  
Hiv 1

Background: HIV-1 Nef is an important accessory protein with multiple effector functions. Genetic studies of HIV-1 Nef gene shows extensive genetic diversity and the functional studies have been carried out mostly with Nef derived from regions dominated by subtype B (North America & Europe). Objective: This study was carried out to characterize genetic variations of the Nef gene from HIV-1 infected individuals from North-India and to find out their functional implications. Methods: The unique representative variants were sub-cloned in eukaryotic expression vector and further characterized with respect to their ability to down regulate cell surface expression of CD4 and MHC-1molecules. Results: The phylogenetic analysis of Nef variants revealed sequence similarity with either consensus subtype B or B/C recombinants. Boot scan analysis of some of our variants showed homology to B/C recombinant and some to wild type Nef B. Extensive variations were observed in most of the variants. The dN/dS ratio revealed 80% purifying selection and 20% diversifying selection implying the importance of mutations in Nef variants. Intracellular stability of Nef variants differed greatly when compared with wild type Nef B and C. There were some variants that possessed mutations in the functional domains of Nef and responsible for its differential CD4 and MHC-1 down regulation activity. Conclusion: We observed enhanced biological activities in some of the variants, perhaps arising out of amino acid substitutions in their functional domains. The CD4 and MHC-1 down-regulation activity of Nef is likely to confer immense survival advantage allowing the most rare genotype in a population to become the most abundant after a single selection event.

scholarly journals Gene set enrichment analysis for genome-wide DNA methylation data

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jovana Maksimovic ◽  
Alicia Oshlack ◽  
Belinda Phipson
Keyword(s):  
Dna Methylation ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Methylation Array ◽  
Gene Set ◽  
Genome Wide ◽  
Genome Methylation ◽  
Unbiased Gene ◽  
Gene Set Testing

AbstractDNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalization, and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches, and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.

scholarly journals MiR-217 is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation by down-regulation of SIRT1

2012 ◽  
Vol 1823 (5) ◽  
pp. 1017-1023 ◽  
Author(s):  
Hong-Sheng Zhang ◽  
Tong-Chao Wu ◽  
Wei-Wei Sang ◽  
Zheng Ruan
Keyword(s):  
Long Terminal Repeat ◽  
Terminal Repeat ◽  
Down Regulation ◽  
Hiv 1

scholarly journals Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1

2017 ◽  
Vol 13 (11) ◽  
pp. e1006703 ◽  
Author(s):  
Romel D. Mackelprang ◽  
Michael J. Bamshad ◽  
Jessica X. Chong ◽  
Xuanlin Hou ◽  
Kati J. Buckingham ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Increased Risk ◽  
Extreme Phenotypes ◽  
Hiv 1

scholarly journals Performance of a high-throughput next-generation sequencing method for analysis of HIV drug resistance and viral load

2020 ◽  
Vol 75 (12) ◽  
pp. 3510-3516 ◽  
Author(s):  
Jessica M Fogel ◽  
David Bonsall ◽  
Vanessa Cummings ◽  
Rory Bowden ◽  
Tanya Golubchik ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Next Generation Sequencing ◽  
High Throughput ◽  
Whole Genome ◽  
Hiv Viral Load ◽  
Viral Loads ◽  
Viral Load Assay ◽  
Generation Sequencing ◽  
Hiv 1

Abstract Objectives To evaluate the performance of a high-throughput research assay for HIV drug resistance testing based on whole genome next-generation sequencing (NGS) that also quantifies HIV viral load. Methods Plasma samples (n = 145) were obtained from HIV-positive MSM (HPTN 078). Samples were analysed using clinical assays (the ViroSeq HIV-1 Genotyping System and the Abbott RealTime HIV-1 Viral Load assay) and a research assay based on whole-genome NGS (veSEQ-HIV). Results HIV protease and reverse transcriptase sequences (n = 142) and integrase sequences (n = 138) were obtained using ViroSeq. Sequences from all three regions were obtained for 100 (70.4%) of the 142 samples using veSEQ-HIV; results were obtained more frequently for samples with higher viral loads (93.5% for 93 samples with &gt;5000 copies/mL; 50.0% for 26 samples with 1000–5000 copies/mL; 0% for 23 samples with &lt;1000 copies/mL). For samples with results from both methods, drug resistance mutations (DRMs) were detected in 33 samples using ViroSeq and 42 samples using veSEQ-HIV (detection threshold: 5.0%). Overall, 146 major DRMs were detected; 107 were detected by both methods, 37 were detected by veSEQ-HIV only (frequency range: 5.0%–30.6%) and two were detected by ViroSeq only. HIV viral loads estimated by veSEQ-HIV strongly correlated with results from the Abbott RealTime Viral Load assay (R2 = 0.85; n = 142). Conclusions The NGS-based veSEQ-HIV method provided results for most samples with higher viral loads, was accurate for detecting major DRMs, and detected mutations at lower levels compared with a method based on population sequencing. The veSEQ-HIV method also provided HIV viral load data.

scholarly journals Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation

1997 ◽  
Vol 16 (23) ◽  
pp. 6964-6976 ◽  
Author(s):  
M. E. Greenberg
Keyword(s):  
Protein Complex ◽  
Adaptor Protein ◽  
Down Regulation ◽  
Hiv 1
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