Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data

Dai, Manhong; Wang, Pinglang; Boyd, Andrew D.; Kostov, Georgi; Athey, Brian D.; Jones, Edward G.; Bunney, William E.; Myers, R; Speed, T. P.; Akil, Huda; Watson, Stanley J.; Meng, Fandong

doi:10.1093/nar/gni179

Cited by 1,630 publications

(1,522 citation statements)

References 22 publications

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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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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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“…Probe sets were defined according to Dai et al. 45. In this method probes are assigned to unique gene identifiers, in this case Entrez IDs.…”

Section: Methodsmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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“…57 Custom CDF were used and downloaded from brainarray website. 58 miRNA raw data was log 2 transformed for normalization. An integrative network including miRNA and differentially expressed genes between subtypes was built and visualized using miRNet 59 and the Gephi software, 60 respectively.…”

Section: Methodsmentioning

confidence: 99%

Immunological and classical subtypes of oral premalignant lesions

et al. 2018

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Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality and may develop from oral premalignant lesions (OPL). An improved molecular classification of OPL may help refining prevention strategies. We identified two main OPL gene-expression subtypes, named immunological and classical, in 86 OPL (discovery dataset). A gene expression-based score was then developed to classify OPL samples from three independent datasets, including 17 (GSE30784),13 (GSE10174) and 15 (GSE85195) OPLs, into either one of the two gene-expression subtypes. Using the single sample gene set enrichment analysis, enrichment scores for immune-related pathways were different between the two OPL subtypes. In OPL from the discovery set, loss of heterozygosities (LOH) at 3p14, 17p13, TP53, 9p21 and 8p22 and miRNA gene expression profiles were analyzed. Deconvolution of the immune infiltrate was performed using the Microenvironment Cell Populations-counter tool. A multivariate analysis revealed that decreased miRNA-142-5p expression (P = 0.0484) and lower T-cell, monocytic and myeloid dendritic cells (MDC) immune infiltration (T-cells, P = 0.0196; CD8 T cells, P = 0.0129; MDC, P = 0.0481; and monocytes, P = 0.0212) were associated with oral cancer development in the immunological subtype only. In contrast, LOH at 3p14 (P = 0.0241), 17p13 (P = 0.0348) and TP53 (P = 0.004) were associated with oral cancer development in the classical subtype only. In conclusion, we identified 2 subtypes of OPLs, namely immune and classical, which may benefit from different and specific personalized prevention interventions.

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Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data

Cited by 1,630 publications

References 22 publications

Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity

Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Immunological and classical subtypes of oral premalignant lesions

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