affy—analysis of <i>Affymetrix GeneChip</i> data at the probe level

Gautier, Laurent; Cope, Leslie; Bolstad, Benjamin M.; Irizarry, Rafael A.

doi:10.1093/bioinformatics/btg405

Cited by 4,710 publications

(3,804 citation statements)

References 15 publications

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“…The microarray data were downloaded from NCBI GEO (Barrett et al, 2013) using the accession numbers in Supporting Information Table S1. Using “affy” (Gautier, Cope, Bolstad, & Irizarry, 2004) or “oligo” (Carvalho & Irizarry, 2010) libraries in r , RMA background correction is applied to the expression data. The data are then log2‐transformed and quantile‐normalized (using “preprocessCore” library in r ).…”

Section: Methodsmentioning

confidence: 99%

Gene expression‐based drug repurposing to target aging

et al. 2018

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Aging is the largest risk factor for a variety of noncommunicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both lifespan and healthspan. Aging is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target‐centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat aging in human brain. Using multiple gene expression data sets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterize aging. Then, we compared these changes in gene expression with drug‐perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as antiaging drugs by reversing the detrimental changes that occur during aging, others by mimicking the cellular defence mechanisms. The drugs that we identified included significant number of already identified prolongevity drugs, indicating that the method can discover de novo drugs that meliorate aging. The approach has the advantages that using data from human brain aging data, it focuses on processes relevant in human aging and that it is unbiased, making it possible to discover new targets for aging studies.

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Section: Methodsmentioning

confidence: 99%

Gene expression‐based drug repurposing to target aging

et al. 2018

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“…CEL files were normalized to produce gene‐level expression values using the implementation of the Robust Multiarray Average algorithm in the affy package (version 1.36.1) included in the Bioconductor software suite (version 2.12) and an Entrez Gene‐specific probeset mapping (version 17.0.0) from the Molecular and Behavioral Neuroscience Institute (Brainarray) at the University of Michigan 20, 21, 22, 23…”

Section: Methodsmentioning

confidence: 99%

Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity

Luther

Gala

Masia

et al. 2018

Hepatology Communications

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Emerging data highlight the critical role for the innate immune system in the progression of nonalcoholic fatty liver disease (NAFLD). Connexin 32 (Cx32), the primary liver gap junction protein, is capable of modulating hepatic innate immune responses and has been studied in dietary animal models of steatohepatitis. In this work, we sought to determine the association of hepatic Cx32 with the stages of human NAFLD in a histologically characterized cohort of 362 patients with NAFLD. We also studied the hepatic expression of the genes and proteins known to interact with Cx32 (known as the connexome) in patients with NAFLD. Last, we used three independent dietary mouse models of nonalcoholic steatohepatitis to investigate the role of Cx32 in the development of steatohepatitis and fibrosis. In a univariate analysis, we found that Cx32 hepatic expression associates with each component of the NAFLD activity score and fibrosis severity. Multivariate analysis revealed that Cx32 expression most closely associated with the NAFLD activity score and fibrosis compared to known risk factors for the disease. Furthermore, by analyzing the connexome, we identified novel genes related to Cx32 that associate with NAFLD progression. Finally, we demonstrated that Cx32 deficiency protects against liver injury, inflammation, and fibrosis in three murine models of nonalcoholic steatohepatitis by limiting initial diet‐induced hepatoxicity and subsequent increases in intestinal permeability. Conclusion: Hepatic expression of Cx32 strongly associates with steatohepatitis and fibrosis in patients with NAFLD. We also identify novel genes associated with NAFLD and suggest that Cx32 plays a role in promoting NAFLD development. (Hepatology Communications 2018;2:786‐797)

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“…All experiments were performed according to the manufacturer's recommended protocol. In addition, we performed background correction, summarization, and normalization using the RMA function in the Bioconductor package 16. We compared microRNA expression in tissues with FCD type II and controls using RankProd (Bioconductor package) software and false discovery rate correction for multiple comparisons.…”

Section: Methodsmentioning

confidence: 99%

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

Avansini

Torres

Vieira

et al. 2018

Annals of Neurology

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ObjectiveFocal cortical dysplasias (FCDs) are an important cause of drug‐resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II.MethodsWe used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study.Resultshsa‐let‐7f (p = 0.039), hsa‐miR‐31 (p = 0.0078), and hsa‐miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2‐target, is upregulated (p < 0.001). In vitro experiments showed that hsa‐miR‐34a downregulates NEUROG2 by binding to its 5′‐untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway.InterpretationOur findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa‐miR‐34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623–635

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affy—analysis of Affymetrix GeneChip data at the probe level

Cited by 4,710 publications

References 15 publications

Gene expression‐based drug repurposing to target aging

Gene expression‐based drug repurposing to target aging

Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

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