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Consistent across-tissue signatures of differential gene expression in Crohn's disease.

ABSTRACT: An approach based on analysis of variance was applied to raw expression data on 44,760 transcripts in order to identify those with significant differential expression across ileum and colon in Crohn's disease (CD) and ulcerative colitis (UC). The design treated tissue as a block effect, thereby removing this effect statistically and increasing the power to test for effects of disease states (control, CD, and UC). A significant F-statistic for the disease effect was not correlated with the ratios CD/control or UC/control, evidently because many transcripts with high-expression ratios to the control showed inconsistent patterns across tissues. Of 1,053 transcripts showing a significant effect of disease state at the 1% level by the bootstrap test, 508 showed significant difference at the 1% level in a post hoc test for difference between the mean scores for CD and control. These included a number of genes relevant to the mechanism of pathogenesis of CD and a number of genes mapping to genomic regions that have previously shown linkage to CD in association studies.

SUBMITTER: Hughes AL

PROVIDER: S-EPMC1440924 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature

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Consistent across-tissue signatures of differential gene expression in Crohn's disease.

Hughes Austin L AL

Immunogenetics 20051108 10

An approach based on analysis of variance was applied to raw expression data on 44,760 transcripts in order to identify those with significant differential expression across ileum and colon in Crohn's disease (CD) and ulcerative colitis (UC). The design treated tissue as a block effect, thereby removing this effect statistically and increasing the power to test for effects of disease states (control, CD, and UC). A significant F-statistic for the disease effect was not correlated with the ratios ...[more]

PMID: 16189665

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Project description:PurposeTo identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers.MethodsWe conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers.ResultsThe principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803-0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981-0.984). The results of validation revealed that four tissue metabolites: N1,N12-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863.ConclusionsThese data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders.

Dataset Information

Consistent across-tissue signatures of differential gene expression in Crohn's disease.

Publications

Consistent across-tissue signatures of differential gene expression in Crohn's disease.

Similar Datasets

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