Transcriptome meta-analysis identifies immune signature comprising of RNA binding proteins in ulcerative colitis patients

Naz, Sumera; Khan, Rafiq Ahmad; Giddaluru, Jeevan; Battu, Srikanth; Vishwakarma, Sandeep Kumar; Subahan, Mabu P.; Satti, Vishnupriya; Khan, Nooruddin; Khan, Aleem Ahmed

doi:10.1016/j.cellimm.2018.09.003

Cited by 13 publications

(13 citation statements)

References 24 publications

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“…Zhu et al performed Robust Rank Aggregation on gene lists from 14 publicly available datasets with 100 up-regulated and 50 down-regulated genes and identified 7 enrichment modules that are similar to the pathways identified in this study 11 . Other investigators have used meta- analysis to study gene expression in blood or peripheral blood mononuclear cells 9 , 10 , or to compare CD and UC 8 , or response to therapy 35 . The current study advances the field with the analysis of a non-redundant set of samples (those represented in multiple datasets were excluded) and methods that both visualize the contribution of individual datasets to the meta-analysis, and facilitate direct comparison of the confidence intervals for log2-FC between datasets.…”

Section: Discussionmentioning

confidence: 99%

“…Several publicly available transcriptomics datasets exist from patients with UC and healthy controls. Meta-analysis of data from multiple studies has been undertaken using various methodologies to explore the similarities between Crohn’s disease (CD) and UC 8 , 9 , to define disease signatures in peripheral blood mononuclear cells from patients with UC 10 , and to identify disease signatures associated with UC pathogenesis 11 .…”

Section: Introductionmentioning

confidence: 99%

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Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis

Linggi¹,

Jairath

Zou

et al. 2021

Sci Rep

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Publicly available ulcerative colitis (UC) gene expression datasets from observational studies and clinical trials include inherently heterogeneous disease characteristics and methodology. We used meta-analysis to identify a robust UC gene signature from inflamed biopsies. Eight gene expression datasets derived from biopsy tissue samples from noninflammatory bowel disease (IBD) controls and areas of active inflammation from patients with UC were publicly available. Expression- and meta-data were downloaded with GEOquery. Differentially expressed genes (DEG) in individual datasets were defined as those with fold change > 1.5 and a Benjamini–Hochberg adjusted P value < .05. Meta-analysis of all DEG used a random effects model. Reactome pathway enrichment analysis was conducted. Meta-analysis identified 946 up- and 543 down-regulated genes in patients with UC compared to non-IBD controls (1.2 and 1.7 times fewer up- and down-regulated genes than the median of the individual datasets). Top-ranked up- and down-regulated DEG were LCN2 and AQP8. Multiple immune-related pathways (e.g., ‘Chemokine receptors bind chemokine’ and ‘Interleukin-10 signaling’) were significantly up-regulated in UC, while ‘Biological oxidations’ and ‘Fatty acid metabolism’ were downregulated. A web-based data-mining tool with the meta-analysis results was made available (https://premedibd.com/genes.html). A UC inflamed biopsy disease gene signature was derived. This signature may be an unbiased reference for comparison and improve the efficiency of UC biomarker studies by increasing confidence for identification of disease-related genes and pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis

Linggi¹,

Jairath

Zou

et al. 2021

Sci Rep

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“…Different meta-analyses of IBD patient gene expression pro les from microarray datasets have already identi ed dysregulation of expression of genes encoding for several in ammatory factors and RNAbinding proteins [3][4][5] . Nevertheless, these studies focused on a limited number of genes, lacking not only the whole-transcriptome but also metatranscriptome pro ling, the latter newly emerged as successful to uncover novel gut-populating microbial entities 6 .…”

Section: Resultsmentioning

confidence: 99%

Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework

Massimino

Lamparelli

Houshyar

et al. 2021

Preprint

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Inflammatory bowel disease (IBD) is a class of chronic inflammatory gut disorders whose aetiogenesis is still unknown. Despite the high number of omics studies, the RNA sequencing (RNA-Seq) data produced for a better IBD pathogenesis understanding cannot be compared because of the experimental variability and different data analysis approaches. To overcome this hurdle, we here introduce the open-source IBD Transcriptome and Metatranscriptome Meta-Analysis (TaMMA) framework, a comprehensive survey of publicly available IBD RNA-Seq datasets. IBD TaMMA will expedite the profiling of the IBD-associated transcriptome and metatranscriptome, holding out the strong promise of being of high impact for the IBD community.

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“…Several of the ALP genes we found consistently epigenetically suppressed across the PD gut and brain have direct roles in inhibiting inflammation under physiologically normal conditions 51 , 67 , 109 – 115 . In addition, two of the top dysregulated ALP genes, TIAL1 and CALCOCO2 , have been implicated as key factors in ulcerative colitis- and Crohn’s disease-related inflammation, respectively 67 , 112 . There is also evidence for the involvement of α-syn in rallying an immune response in the GI tract in response to infection 116 , and that α-syn is upregulated in response to viral 117 and bacterial infections 118 .…”

Section: Discussionmentioning

confidence: 99%

Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease

Gordevičius

Marshall

et al. 2021

Nat Commun

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The gastrointestinal tract may be a site of origin for α-synuclein pathology in idiopathic Parkinson’s disease (PD). Disruption of the autophagy-lysosome pathway (ALP) may contribute to α-synuclein aggregation. Here we examined epigenetic alterations in the ALP in the appendix by deep sequencing DNA methylation at 521 ALP genes. We identified aberrant methylation at 928 cytosines affecting 326 ALP genes in the appendix of individuals with PD and widespread hypermethylation that is also seen in the brain of individuals with PD. In mice, we find that DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by α-synuclein pathology. DNA methylation changes at ALP genes induced by synucleinopathy are associated with the ALP abnormalities observed in the appendix of individuals with PD specifically involving lysosomal genes. Our work identifies epigenetic dysregulation of the ALP which may suggest a potential mechanism for accumulation of α-synuclein pathology in idiopathic PD.

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Transcriptome meta-analysis identifies immune signature comprising of RNA binding proteins in ulcerative colitis patients

Cited by 13 publications

References 24 publications

Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis

Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis

Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework

Epigenetic inactivation of the autophagy–lysosomal system in appendix in Parkinson’s disease

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