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https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#1
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28081581/differences-in-gene-expression-and-gene-associations-in-epicardial-fat-compared-to-subcutaneous-fat
#2
J Yim, S W Rabkin
Epicardial adipose tissue (EAT) plays a role in cardiac physiology and may contribute to the development of coronary artery disease. Our objective was to determine whether there was a significant difference in gene expression in EAT compared to subcutaneous adipose tissue (SAT) and to identify potential relationships. MEDLINE and EMBASE were searched using the key terms "Epicardial Adipose Tissue" or "Epicardial Fat" in combination with "RNA", "mRNA", or "gene". The entry criteria were studies that presented primary data including expression levels of mRNA in human EAT compared with SAT and an expression of variance (SD)...
January 12, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28079285/a-pathway-based-association-study-reveals-variants-from-wnt-signaling-genes-contributing-to-asthma-susceptibility
#3
A Barreto-Luis, A Corrales, M Acosta-Herrera, C Gonzalez-Colino, J Cumplido, J Martinez-Tadeo, A Carracedo, J Villar, T Carrillo, M Pino-Yanes, C Flores
BACKGROUND: Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. OBJECTIVE: To reveal novel asthma susceptibility genes by means of a pathway-based association study. METHODS: Based on summary data from a previous a genome-wide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis...
January 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28077804/the-complex-genetics-of-gait-speed-genome-wide-meta-analysis-approach
#4
Dan Ben-Avraham, David Karasik, Joe Verghese, Kathryn L Lunetta, Jennifer A Smith, John A Eicher, Rotem Vered, Joris Deelen, Alice M Arnold, Aron S Buchman, Toshiko Tanaka, Jessica D Faul, Maria Nethander, Myriam Fornage, Hieab H Adams, Amy M Matteini, Michele L Callisaya, Albert V Smith, Lei Yu, Philip L De Jager, Denis A Evans, Vilmundur Gudnason, Albert Hofman, Alison Pattie, Janie Corley, Lenore J Launer, Davis S Knopman, Neeta Parimi, Stephen T Turner, Stefania Bandinelli, Marian Beekman, Danielle Gutman, Lital Sharvit, Simon P Mooijaart, David C Liewald, Jeanine J Houwing-Duistermaat, Claes Ohlsson, Matthijs Moed, Vincent J Verlinden, Dan Mellström, Jos N van der Geest, Magnus Karlsson, Dena Hernandez, Rebekah McWhirter, Yongmei Liu, Russell Thomson, Gregory J Tranah, Andre G Uitterlinden, David R Weir, Wei Zhao, John M Starr, Andrew D Johnson, M Arfan Ikram, David A Bennett, Steven R Cummings, Ian J Deary, Tamara B Harris, Sharon L R Kardia, Thomas H Mosley, Velandai K Srikanth, Beverly G Windham, Ann B Newman, Jeremy D Walston, Gail Davies, Daniel S Evans, Eline P Slagboom, Luigi Ferrucci, Douglas P Kiel, Joanne M Murabito, Gil Atzmon
Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues...
January 10, 2017: Aging
https://www.readbyqxmd.com/read/28073927/new-insights-into-the-genetics-of-primary-open-angle-glaucoma-based-on-meta-analyses-of-intraocular-pressure-and-optic-disc-characteristics
#5
Henriët Springelkamp, Adriana I Iglesias, Aniket Mishra, René Höhn, Robert Wojciechowski, Anthony P Khawaja, Abhishek Nag, Ya Xing Wang, Jie Jin Wang, Gabriel Cuellar-Partida, Jane Gibson, Jessica N Cooke Bailey, Eranga N Vithana, Puya Gharahkhani, Thibaud Boutin, Wishal D Ramdas, Tanja Zeller, Robert N Luben, Ekaterina Yonova-Doing, Ananth C Viswanathan, Seyhan Yazar, Angela J Cree, Jonathan L Haines, Jia Yu Koh, Emmanuelle Souzeau, James F Wilson, Najaf Amin, Christian Müller, Cristina Venturini, Lisa S Kearns, Jae Hee Kang, Neighborhood Consortium, Yih Chung Tham, Tiger Zhou, Elisabeth M van Leeuwen, Stefan Nickels, Paul Sanfilippo, Jiemin Liao, Herma van der Linde, Wanting Zhao, Leonieke M E van Koolwijk, Li Zheng, Fernando Rivadeneira, Mani Baskaran, Sven J van der Lee, Shamira Perera, Paulus T V M de Jong, Ben A Oostra, André G Uitterlinden, Qiao Fan, Albert Hofman, E- Shyong Tai, Johannes R Vingerling, Xueling Sim, Roger C W Wolfs, Yik Ying Teo, Hans G Lemij, Chiea Chuen Khor, Rob Willemsen, Karl J Lackner, Tin Aung, Nomdo M Jansonius, Grant Montgomery, Philipp S Wild, Terri L Young, Kathryn P Burdon, Pirro G Hysi, Louis R Pasquale, Tien Yin Wong, Caroline C W Klaver, Alex W Hewitt, Jost B Jonas, Paul Mitchell, Andrew J Lotery, Paul J Foster, Veronique Vitart, Norbert Pfeiffer, Jamie E Craig, David A Mackey, Christopher J Hammond, Janey L Wiggs, Ching-Yu Cheng, Cornelia M van Duijn, Stuart MacGregor
Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP...
January 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28067908/genome-wide-association-study-implicates-immune-activation-of-multiple-integrin-genes-in-inflammatory-bowel-disease
#6
Katrina M de Lange, Loukas Moutsianas, James C Lee, Christopher A Lamb, Yang Luo, Nicholas A Kennedy, Luke Jostins, Daniel L Rice, Javier Gutierrez-Achury, Sun-Gou Ji, Graham Heap, Elaine R Nimmo, Cathryn Edwards, Paul Henderson, Craig Mowat, Jeremy Sanderson, Jack Satsangi, Alison Simmons, David C Wilson, Mark Tremelling, Ailsa Hart, Christopher G Mathew, William G Newman, Miles Parkes, Charlie W Lees, Holm Uhlig, Chris Hawkey, Natalie J Prescott, Tariq Ahmad, John C Mansfield, Carl A Anderson, Jeffrey C Barrett
Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28065468/the-genetic-architecture-of-gene-expression-in-peripheral-blood
#7
Luke R Lloyd-Jones, Alexander Holloway, Allan McRae, Jian Yang, Kerrin Small, Biao Zeng, Andrew Bakshi, Andres Metspalu, Manolis Dermitzakis, Greg Gibson, Tim Spector, Grant Montgomery, Tonu Esko, Peter M Visscher, Joseph E Powell
We analyzed the mRNA levels for 36,778 transcript expression traits (probes) from 2,765 individuals to comprehensively investigate the genetic architecture and degree of missing heritability for gene expression in peripheral blood. We identified 11,204 cis and 3,791 trans independent expression quantitative trait loci (eQTL) by using linear mixed models to perform genome-wide association analyses. Furthermore, using information on both closely and distantly related individuals, heritability was estimated for all expression traits...
December 24, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28060761/identification-of-micrornas-associated-with-glioma-diagnosis-and-prognosis
#8
Xinyun Ye, Wenjin Wei, Zhengyu Zhang, Chunming He, Ruijin Yang, Jinshi Zhang, Zhiwu Wu, Qianliang Huang, Qiuhua Jiang
The sensitivity and specificity of microRNAs (miRNAs) for diagnosing glioma are controversial. We therefore performed a meta-analysis to systematically identify glioma-associated miRNAs. We initially screened five miRNA microarray datasets to evaluate the differential expression of miRNAs between glioma and normal tissues. We next compared the expression of the miRNAs in different organs and tissues to assess the sensitivity and specificity of the differentially expressed miRNAs in the diagnosis of glioma. Finally, pathway analysis was performed using GeneGO...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060730/prognostic-value-of-micrornas-in-osteosarcoma-a-meta-analysis
#9
Yun Hak Kim, Tae Sik Goh, Chi-Seung Lee, Sae Ock Oh, Jeung Il Kim, Seung Hyeon Jeung, Kyoungjune Pak
BACKGROUND: Osteosarcoma is the most common primary bone malignancy. We meta-analyzed the prognostic value of altered miRNAs in patients with osteosarcoma. METHODS: Sources from MEDLINE (from inception to August 2016) and EMBASE (from inception to August 2016) were searched. Studies of osteosarcoma with results of miRNA and studies that reported survival data were included and two authors performed the data extraction independently. Any discrepancies were resolved by a consensus...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28056781/meta-analysis-reveals-conserved-cell-cycle-transcriptional-network-across-multiple-human-cell-types
#10
Bruno Giotti, Anagha Joshi, Tom C Freeman
BACKGROUND: Cell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28053291/sparc-expression-in-gastric-cancer-predicts-poor-prognosis-results-from-a-clinical-cohort-pooled-analysis-and-gsea-assay
#11
Zhi Li, Ao-Di Li, Lu Xu, De-Wei Bai, Ke-Zuo Hou, Hua-Chuan Zheng, Xiu-Juan Qu, Yun-Peng Liu
BACKGROUND: The prognostic role of Secreted Protein Acidic and Rich in Cysteine (SPARC) in gastric cancer (GC) remains controversial. We investigated the clinical significance, the survival relevance, and potential function of SPARC in GC with resected samples, online gene set GSE62254, and cell line SGC7901. RESULTS: High immunostaining of SPARC significantly correlated with tumor differentiation (P = 0.004), and independently predicted shorter overall survival (OS) (HR = 1...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051114/novel-therapeutics-identification-for-fibrosis-in-renal-allograft-using-integrative-informatics-approach
#12
Li Li, Ilana Greene, Benjamin Readhead, Madhav C Menon, Brian A Kidd, Andrew V Uzilov, Chengguo Wei, Nimrod Philippe, Bernd Schroppel, John Cijiang He, Rong Chen, Joel T Dudley, Barbara Murphy
Chronic allograft damage, defined by interstitial fibrosis and tubular atrophy (IF/TA), is a leading cause of allograft failure. Few effective therapeutic options are available to prevent the progression of IF/TA. We applied a meta-analysis approach on IF/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF/TA...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28051079/genome-wide-association-scan-of-neuropathic-pain-symptoms-post-total-joint-replacement-highlights-a-variant-in-the-protein-kinase-c-gene
#13
Sophie C Warner, Joyce Bj van Meurs, Dieuwke Schiphof, Sita M Bierma-Zeinstra, Albert Hofman, Andre G Uitterlinden, Helen Richardson, Wendy Jenkins, Michael Doherty, Ana M Valdes
Neuropathic pain-like joint symptoms (NP) are seen in a proportion of individuals diagnosed with osteoarthritis (OA) and post total joint replacement (TJR). In this study, we performed a genome-wide association study (GWAS) using NP as defined by the painDETECT questionnaire (score >12 indicating possible NP) in 613 post-TJR participants recruited from Nottinghamshire (UK). The prevalence of possible NP was 17.8%. The top four hits from the GWAS and two other biologically relevant single-nucleotide polymorphisms (SNPs) were replicated in individuals with OA and post TJR from an independent study in the same area (N=908) and in individuals from the Rotterdam Study (N=212)...
January 4, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28036281/the-prognostic-value-of-long-noncoding-rna-hottip-on-clinical-outcomes-in-breast-cancer
#14
Yinlong Yang, Jinxian Qian, Youqun Xiang, Yizuo Chen, Jinmiao Qu
Although a few studies have assessed the prognostic value of long noncoding RNA HOTTIP in patients with malignant tumors, the relationship between HOTTIP and clinical outcome of breast cancer remains elusive. The aim of this study is to explore the prognostic significance of HOTTIP in breast cancer patients. A meta-analysis was performed to involve the eligible studies to investigate the association of HOTTIP expression level with outcome in cancer patients. Pooled hazard ratios (HRs) and 95% confidence interval (CI) of HOTTIP for cancer survival were calculated...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28033256/identified-molecular-mechanism-of-interaction-between-environmental-risk-factors-and-differential-expression-genes-in-cartilage-of-kashin-beck-disease
#15
Fang-Fang Yu, Yan-Xiang Zhang, Lian-He Zhang, Wen-Rong Li, Xiong Guo, Mikko J Lammi
As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28031185/metadcn-meta-analysis-framework-for-differential-co-expression-network-detection-with-an-application-in-breast-cancer
#16
Li Zhu, Ying Ding, Cho-Yi Chen, Lin Wang, Zhiguang Huo, SungHwan Kim, Christos Sotiriou, Steffi Oesterreich, George C Tseng
MOTIVATION: Gene co-expression network analysis from transcriptomic studies can elucidate genegene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results...
December 28, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28029757/identification-of-functional-and-expression-polymorphisms-associated-with-risk-for-anti-neutrophil-cytoplasmic-autoantibody-associated-vasculitis
#17
Peter A Merkel, Gang Xie, Paul A Monach, Xuemei Ji, Dominic J Ciavatta, Jinyoung Byun, Benjamin D Pinder, Ai Zhao, Jinyi Zhang, Yohannes Tadesse, David Qian, Matthew Weirauch, Rajan Nair, Alex Tsoi, Christian Pagnoux, Simon Carette, Sharon Chung, David Cuthbertson, John C Davis, Paul F Dellaripa, Lindsy Forbess, Ora Gewurz-Singer, Gary S Hoffman, Nader Khalidi, Curry Koening, Carol A Langford, Alfred D Mahr, Carol McAlear, Larry Moreland, E Philip Seo, Ulrich Specks, Robert F Spiera, Antoine Sreih, E William St Clair, John H Stone, Steven R Ytterberg, James T Elder, Jia Qu, Toshiki Ochi, Naoto Hirano, Jeffrey C Edberg, Ronald J Falk, Christopher I Amos, Katherine A Siminovitch
OBJECTIVE: To identify risk alleles relevant to the cause and biology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We conducted a genome-wide association and subsequent replication study including 1986 cases of AAV [granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)] and 4723 controls. Meta-analysis of these datasets and functional annotation of identified risk loci were performed and candidate disease variants with unknown functional effects investigated for impact on gene expression and/or protein function...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28029629/discovering-perturbation-of-modular-structure-in-hiv-progression-by-integrating-multiple-data-sources-through-non-negative-matrix-factorization
#18
Sumanta Ray, Ujjwal Maulik
Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF)...
December 20, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28011145/a-functional-genomic-meta-analysis-of-clinical-trials-in-systemic-sclerosis-towards-precision-medicine-and-combination-therapy
#19
Jaclyn N Taroni, Viktor Martyanov, J Matthew Mahoney, Michael L Whitfield
Systemic sclerosis (SSc) is an orphan, systemic autoimmune disease with no FDA-approved treatments. Its heterogeneity and rarity often result in underpowered clinical trials making the analysis and interpretation of associated molecular data challenging. We performed a meta-analysis of gene expression data from skin biopsies of SSc patients treated with five therapies: mycophenolate mofetil (MMF), rituximab, abatacept, nilotinib, and fresolimumab. A common clinical improvement criterion of -20% OR -5 modified Rodnan Skin Score was applied to each study...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27997584/prediction-of-possible-biomarkers-and-novel-pathways-conferring-risk-to-post-traumatic-stress-disorder
#20
Kumaraswamy Naidu Chitrala, Prakash Nagarkatti, Mitzi Nagarkatti
Post-traumatic stress disorder is one of the common mental ailments that is triggered by exposure to traumatic events. Till date, the molecular factors conferring risk to the development of PTSD is not well understood. In this study, we have conducted a meta-analysis followed by hierarchical clustering and functional enrichment, to uncover the potential molecular networks and critical genes which play an important role in PTSD. Two datasets of expression profiles from Peripheral Blood Mononuclear Cells from 62 control samples and 63 PTSD samples were included in our study...
2016: PloS One
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