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transcriptome and meta-analysis

Ali Nehme, Catherine Cerutti, Kazem Zibara
Despite the well-known role of the renin-angiotensin-aldosterone system (RAAS) in atheroma, its global local organization is poorly understood. In this study, we used transcriptomic meta-analysis to reveal the local transcriptional organization and regulation of 37 extended RAAS (extRAAS) genes in atheroma. Expression analysis and hierarchical clustering were done on extRAAS genes in 32 paired early and advanced atherosclerotic lesions. Contrary to receptor-coding transcripts, multiple angiotensin-metabolizing enzymes showed higher expression in advance, in comparison to early lesions...
October 17, 2016: Hypertension
Jing-Woei Li, Heung-Man Lee, Ying Wang, Amy Hin-Yan Tong, Kevin Y Yip, Stephen Kwok-Wing Tsui, Si Lok, Risa Ozaki, Andrea O Luk, Alice P S Kong, Wing-Yee So, Ronald C W Ma, Juliana C N Chan, Ting-Fung Chan
Protein interactions play significant roles in complex diseases. We analyzed peripheral blood mononuclear cells (PBMC) transcriptome using a multi-method strategy. We constructed a tissue-specific interactome (T2Di) and identified 420 molecular signatures associated with T2D-related comorbidity and symptoms, mainly implicated in inflammation, adipogenesis, protein phosphorylation and hormonal secretion. Apart from explaining the residual associations within the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study, the T2Di signatures were enriched in pathogenic cell type-specific regulatory elements related to fetal development, immunity and expression quantitative trait loci (eQTL)...
October 18, 2016: Scientific Reports
Van N T Nguyen, Kieu T X Vo, Hyon Park, Jong-Seong Jeon, Ki-Hong Jung
The Mildew resistance Locus O (MLO) family is unique to plants, containing genes that were initially identified as a susceptibility factor to powdery mildew pathogens. However, little is known about the roles and functional diversity of this family in rice, a model crop plant. The rice genome has 12 potential MLO family members. To achieve systematic functional assignments, we performed a phylogenomic analysis by integrating meta-expression data obtained from public sources of microarray data and real-time expression data into a phylogenic tree...
2016: Frontiers in Plant Science
Liqun He, Michael Vanlandewijck, Elisabeth Raschperger, Maarja Andaloussi Mäe, Bongnam Jung, Thibaud Lebouvier, Koji Ando, Jennifer Hofmann, Annika Keller, Christer Betsholtz
Pericytes, the mural cells of blood microvessels, regulate microvascular development and function and have been implicated in many brain diseases. However, due to a paucity of defining markers, pericyte identification and functional characterization remain ambiguous and data interpretation problematic. In mice carrying two transgenic reporters, Pdgfrb-eGFP and NG2-DsRed, we found that double-positive cells were vascular mural cells, while the single reporters marked additional, but non-overlapping, neuroglial cells...
October 11, 2016: Scientific Reports
Yang Sun, Zhijian Sang, Qian Jiang, Xiaojun Ding, Youcheng Yu
Oral squamous cell carcinoma (OSCC) is a highly prevalent cancer worldwide, and OSCC often goes undiagnosed until advanced disease is present, which contributes to a low survival rate for OSCC patients. The identification of biomarkers for the early detection OSCC and novel therapeutic targets for OSCC treatment is an important research objective. We performed bioinformatics analyses of the gene expression profile of OSCC using microarray data to identify genes that contribute to the development of OSCC. We also predicted the transcription factors involved in the regulation of differential gene expression in OSCC...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
David A Ewald, Shinji Noda, Margeaux Oliva, Thomas Litman, Saeko Nakajima, Xuan Li, Hui Xu, Peter Scheipers, Naila Svitacheva, Tord Labuda, James G Krueger, Mayte Suárez-Fariñas, Kenji Kabashima, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. While many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. OBJECTIVE: We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin...
October 1, 2016: Journal of Allergy and Clinical Immunology
Dijana Djureinovic, Björn M Hallström, Masafumi Horie, Johanna Sofia Margareta Mattsson, Linnea La Fleur, Linn Fagerberg, Hans Brunnström, Cecilia Lindskog, Katrin Madjar, Jörg Rahnenführer, Simon Ekman, Elisabeth Ståhle, Hirsh Koyi, Eva Brandén, Karolina Edlund, Jan G Hengstler, Mats Lambe, Akira Saito, Johan Botling, Fredrik Pontén, Mathias Uhlén, Patrick Micke
Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs...
July 7, 2016: JCI Insight
Jose A Santiago, Alyssa M Littlefield, Judith A Potashkin
Emerging research indicates that depression could be one of the earliest prodromal symptoms or risk factors associated with the pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder worldwide, but the mechanisms underlying the association between both diseases remains unknown. Understanding the molecular networks linking these diseases could facilitate the discovery of novel diagnostic and therapeutics. Transcriptomic meta-analysis and network analysis of blood microarrays from untreated patients with PD and depression identified genes enriched in pathways related to the immune system, metabolism of lipids, glucose, fatty acids, nicotinamide, lysosome, insulin signaling and type 1 diabetes...
September 29, 2016: Scientific Reports
Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London
BACKGROUND: -DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. METHODS AND RESULTS: -To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers)...
September 20, 2016: Circulation. Cardiovascular Genetics
Sumbul Afroz, Jeevan Giddaluru, Mohd Manzar Abbas, Nooruddin Khan
Dengue Viruses (DENVs) cause one of the most prevalent arthropod-borne viral diseases affecting millions of people worldwide. Identification of genes involved in DENV pathogenesis would help in deciphering molecular mechanisms responsible for the disease progression. Here, we carried out a meta-analysis of publicly available gene expression data of dengue patients and further validated the meta-profile using in-vitro infection in THP-1 cells. Our findings reveal that DENV infection modulates expression of several genes and signalling pathways including interferons, detoxification of ROS and viral assembly...
2016: Scientific Reports
Brian H Chen, Marie-France Hivert, Marjolein J Peters, Luke C Pilling, John D Hogan, Lisa M Pham, Lorna W Harries, Caroline S Fox, Stefania Bandinelli, Abbas Dehghan, Dena G Hernandez, Albert Hofman, Jaeyoung Hong, Roby Joehanes, Andrew D Johnson, Peter J Munson, Denis V Rybin, Andrew B Singleton, André G Uitterlinden, Saixia Ying, Magic Investigators, David Melzer, Daniel Levy, Joyce B J van Meurs, Luigi Ferrucci, Jose C Florez, Josée Dupuis, James B Meigs, Eric D Kolaczyk
Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of non-diabetic participants in the Framingham Heart Study (n=5,056), the Rotterdam Study (n=723), and the InCHIANTI Study (n=595). Using a false discovery rate q<0...
September 13, 2016: Diabetes
Marie Tosolini, Christelle Algans, Frédéric Pont, Bernard Ycart, Jean-Jacques Fournié
Non-Hodgkin B-cell lymphoma (B-NHL) are aggressive lymphoid malignancies that develop in patients due to oncogenic activation, chemo-resistance, and immune evasion. Tumor biopsies show that B-NHL frequently uses several immune escape strategies, which has hindered the development of checkpoint blockade immunotherapies in these diseases. To gain a better understanding of B-NHL immune editing, we hypothesized that the transcriptional hallmarks of immune escape associated with these diseases could be identified from the meta-analysis of large series of microarrays from B-NHL biopsies...
July 2016: Oncoimmunology
Douglas Arneson, Anindya Bhattacharya, Le Shu, Ville-Petteri Mäkinen, Xia Yang
BACKGROUND: Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development...
2016: BMC Genomics
Elisa Mariani, Flavia Frabetti, Andrea Tarozzi, Maria Chiara Pelleri, Fabrizio Pizzetti, Raffaella Casadei
The understanding of the genetic basis of the Parkinson's disease (PD) and the correlation between genotype and phenotype has revolutionized our knowledge about the pathogenetic mechanisms of neurodegeneration, opening up exciting new therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in its early stages and can provide a good start for studies of the molecular mechanisms that underlie the gene expression variations and the epigenetic mechanisms that may contribute to the complex and characteristic phenotype of PD...
2016: PloS One
Shane P Duggan, Fiona M Behan, Murat Kirca, Abdul Zaheer, Sarah A McGarrigle, John V Reynolds, Gisela M F Vaz, Mathias O Senge, Dermot Kelleher
Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC...
2016: Scientific Reports
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Moein Yaqubi, Abdulshakour Mohammadnia
Ectopic expression of a defined set of transcription factors (TFs) can directly convert fibroblasts into a cardiac myocyte cell fate. Beside inefficiency in generating induced cardiomyocytes (iCMs), the molecular mechanisms that regulate this process remained to be well defined. The main purpose of this study was to provide better insight on the transcriptome regulation and to introduce a new strategy for candidating TFs for the transdifferentiation process. Eight mouse and three human high quality microarray data sets were analyzed to find differentially expressed genes (DEGs), which we integrated with TF-binding sites and protein-protein interactions to construct gene regulatory and protein-protein interaction networks...
August 31, 2016: Journal of Cellular Physiology
Tianxiao Huan, Roby Joehanes, Claudia Schurmann, Katharina Schramm, Luke C Pilling, Marjolein J Peters, Reedik Mägi, Dawn DeMeo, George T O'Connor, Luigi Ferrucci, Alexander Teumer, Georg Homuth, Reiner Biffar, Uwe Völker, Christian Herder, Melanie Waldenberger, Annette Peters, Sonja Zeilinger, Andres Metspalu, Albert Hofman, André G Uitterlinden, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Peter J Munson, Honghuang Lin, Emelia J Benjamin, Tõnu Esko, Hans J Grabe, Holger Prokisch, Joyce B J van Meurs, David Melzer, Daniel Levy
Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) <0...
August 29, 2016: Human Molecular Genetics
Juan Carlos Higareda-Almaraz, Juan S Ruiz-Moreno, Jana Klimentova, Daniela Barbieri, Raquel Salvador-Gallego, Regina Ly, Ilse A Valtierra-Gutierrez, Christiane Dinsart, Gabriel A Rabinovich, Jiri Stulik, Frank Rösl, Bladimiro Rincon-Orozco
BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations...
2016: BMC Cancer
Kerstin Becker, Sabine Siegert, Mohammad Reza Toliat, Juanjiangmeng Du, Ramona Casper, Guido H Dolmans, Paul M Werker, Sigrid Tinschert, Andre Franke, Christian Gieger, Konstantin Strauch, Michael Nothnagel, Peter Nürnberg, Hans Christian Hennies
Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren´s disease, much of the inherited risk in Dupuytren´s disease still needs to be discovered. The already identified loci jointly explain ~1% of the heritability in this disease...
2016: PloS One
Glyn R Hemsworth, Andrew J Thompson, Judith Stepper, Łukasz F Sobala, Travis Coyle, Johan Larsbrink, Oliver Spadiut, Ethan D Goddard-Borger, Keith A Stubbs, Harry Brumer, Gideon J Davies
The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs)...
July 2016: Open Biology
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