110 results found
Behmoaras J, Petretto E, 2018, Cell function in disease: there are more than two parties at play., Ann Rheum Dis
Cuartero S, Weiss FD, Dharmalingam G, et al., 2018, Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation, NATURE IMMUNOLOGY, Vol: 19, Pages: 932-+, ISSN: 1529-2908
Min ATL, Langley SR, Tan CF, et al., 2018, Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore., J Clin Endocrinol Metab
Context: Insulin resistance (IR) and obesity differ between ethnic groups in Singapore, with the Malays being more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences are not clear. Objective: As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity and related traits. Design, Setting and Main Outcome measures: We integrated transcriptomic, genomic and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study. Patients: This study contains Chinese (n=63), Malay (n=51) and Asian-Indian (n=42) males, aged 21-40 years, without systemic diseases. Results: We found remarkable diversity in the SM transcriptome between the three ethnicities with >8,000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences between ethnicities were unique to SM. We identified a network of 46 genes that were specifically down-regulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene-clusters, four of which were also enriched for genes that were found in GWAS of metabolic traits and disease and correlated with variation in IR, obesity and related traits. Conclusion: We identified extensive gene expression changes in SM between the three Singaporean ethnicities, and report specific genes and molecular pathways that might underpin and explain the differences in IR between these ethnic groups.
Moreno-Moral A, Bagnati M, Koturan S, et al., 2018, Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk, ANNALS OF THE RHEUMATIC DISEASES, Vol: 77, Pages: 596-601, ISSN: 0003-4967
Olona A, Terra X, Ko J-H, et al., 2018, Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis, MOLECULAR METABOLISM, Vol: 11, Pages: 18-32, ISSN: 2212-8778
Pereira M, Petretto E, Gordon S, et al., 2018, Common signalling pathways in macrophage and osteoclast multinucleation, JOURNAL OF CELL SCIENCE, Vol: 131, ISSN: 0021-9533
Rodriguez-Martinez A, Posma JM, Ayala R, et al., 2018, MWASTools: an R/bioconductor package for metabolome-wide association studies, BIOINFORMATICS, Vol: 34, Pages: 890-892, ISSN: 1367-4803
Sigmundsson K, Ojala JRM, Öhman MK, et al., 2018, Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice., Matrix Biol, Vol: 70, Pages: 5-19
The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.
Solimena M, Schulte AM, Marselli L, et al., 2018, Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes, DIABETOLOGIA, Vol: 61, Pages: 641-657, ISSN: 0012-186X
Srivastava PK, van Eyll J, Godard P, et al., 2018, A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Aday S, Halevy I, Anwar M, et al., 2017, Artificial exosomes for post-ischemic vascular regeneration, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 33-33, ISSN: 0195-668X
Anwar M, Saif J, Aday S, et al., 2017, A Bioinformatics Approach Reveals Mechanism of Pericardial Fluid Exosome Action in Promoting Ischemia in Diabetic Patients, Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Beltrami C, Besnier M, Shantikumar S, et al., 2017, Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis, MOLECULAR THERAPY, Vol: 25, Pages: 679-693, ISSN: 1525-0016
Chen T-D, Rotival M, Chiu L-Y, et al., 2017, Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function, GENETICS, Vol: 206, Pages: 1139-1151, ISSN: 0016-6731
Coan PM, Hummel O, Diaz AG, et al., 2017, Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat, DISEASE MODELS & MECHANISMS, Vol: 10, Pages: 297-306, ISSN: 1754-8403
Heinig M, Adriaens ME, Schafer S, et al., 2017, Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy, GENOME BIOLOGY, Vol: 18, ISSN: 1474-760X
Imprialou M, Petretto E, Bottolo L, 2017, Expression QTLs Mapping and Analysis: A Bayesian Perspective., Pages: 189-215
The aim of expression Quantitative Trait Locus (eQTL) mapping is the identification of DNA sequence variants that explain variation in gene expression. Given the recent yield of trait-associated genetic variants identified by large-scale genome-wide association analyses (GWAS), eQTL mapping has become a useful tool to understand the functional context where these variants operate and eventually narrow down functional gene targets for disease. Despite its extensive application to complex (polygenic) traits and disease, the majority of eQTL studies still rely on univariate data modeling strategies, i.e., testing for association of all transcript-marker pairs. However these "one at-a-time" strategies are (1) unable to control the number of false-positives when an intricate Linkage Disequilibrium structure is present and (2) are often underpowered to detect the full spectrum of trans-acting regulatory effects. Here we present our viewpoint on the most recent advances on eQTL mapping approaches, with a focus on Bayesian methodology. We review the advantages of the Bayesian approach over frequentist methods and provide an empirical example of polygenic eQTL mapping to illustrate the different properties of frequentist and Bayesian methods. Finally, we discuss how multivariate eQTL mapping approaches have distinctive features with respect to detection of polygenic effects, accuracy, and interpretability of the results.
Krishnan ML, Van Steenwinckel J, Schang A-L, et al., 2017, Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723
McDermott-Roe C, Leleu M, Rowe GC, et al., 2017, Transcriptome-wide co-expression analysis identifies LRRC2 as a novel mediator of mitochondrial and cardiac function, PLOS ONE, Vol: 12, ISSN: 1932-6203
Moreno-Moral A, Pesce F, Behmoaras J, et al., 2017, Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease., Pages: 337-362
Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.
Nefzger CM, Rossello FJ, Chen J, et al., 2017, Cell Type of Origin Dictates the Route to Pluripotency, CELL REPORTS, Vol: 21, Pages: 2649-2660, ISSN: 2211-1247
Petretto E, 2017, Genetics of Neurodevelopmental Disorders: Connecting The Dots in The Brain, 18th International Congress of Developmental Biology, Publisher: ELSEVIER SCIENCE BV, Pages: S4-S4, ISSN: 0925-4773
Rackham OJL, Langley SR, Oates T, et al., 2017, A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation, GENETICS, Vol: 205, Pages: 1443-1458, ISSN: 0016-6731
Schafer S, Viswanathan S, Widjaja AA, et al., 2017, IL-11 is a crucial determinant of cardiovascular fibrosis, NATURE, Vol: 552, Pages: 110-+, ISSN: 0028-0836
Srivastava PK, Bagnati M, Delahaye-Duriez A, et al., 2017, Genome-wide analysis of differential RNA editing in epilepsy, GENOME RESEARCH, Vol: 27, Pages: 440-450, ISSN: 1088-9051
Srivastava PK, Roncon P, Lukasiuk K, et al., 2017, Meta-Analysis of MicroRNAs Dysregulated in the Hippocampal Dentate Gyrus of Animal Models of Epilepsy, ENEURO, Vol: 4, ISSN: 2373-2822
Suresh J, Harmston N, Lim KK, et al., 2017, An embryonic system to assess direct and indirect Wnt transcriptional targets, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Delahaye-Duriez A, Srivastava P, Shkura K, et al., 2016, Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery, GENOME BIOLOGY, Vol: 17, ISSN: 1474-760X
Diaz-Montana JJ, Rackham OJL, Diaz-Diaz N, et al., 2016, Web-based Gene Pathogenicity Analysis (WGPA): a web platform to interpret gene pathogenicity from personal genome data, BIOINFORMATICS, Vol: 32, Pages: 635-637, ISSN: 1367-4803
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