Open Access Highly Accessed Research article

Independent component and pathway-based analysis of miRNA-regulated gene expression in a model of type 1 diabetes

Claus H Bang-Berthelsen12, Lykke Pedersen3, Tina Fløyel12, Peter H Hagedorn47, Titus Gylvin5 and Flemming Pociot126*

Author Affiliations

1 Glostrup Research Institute, Glostrup University Hospital, DK-2600 Glostrup, Denmark

2 Hagedorn Research Institute, Niels Steensensvej 6, DK-2820 Gentofte, Denmark

3 Center for Models of Life, University of Copenhagen, Blegdamsvej 17, DK-2100 Copenhagen, Denmark

4 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, DK-2800 Lyngby, Denmark

5 Steno Diabetes Center, Niels Steensensvej 2, DK-2820 Gentofte, Denmark

6 University of Lund, CRC, Skåne University Hospital, SE-20502 Malmoe, Sweden

7 Department of Molecular Biomedicine, LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark

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BMC Genomics 2011, 12:97  doi:10.1186/1471-2164-12-97

Published: 4 February 2011

Additional files

Additional file 1:

Expressions of insulin and Pdx-1 dependent genes. There are three experimental conditions: Pdx-1 induction (dox treatment), IL-1β treatment and time (samples are taken 2 h and 24 h after treatment). Log2-transformed fold changes (mean and standard deviation) between experimental and control conditions. *: 0.05 > q > 0.01, **: 0.01 > q > 0.001, ***: 0.001 > q > 0.

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Additional file 2:

miRNA target prediction based on mRNA expression data. For each Ensembl annotated gene on the Affymetrix array is given the gene symbol, gene description, loads in the five ICs, coefficients for correlation with the eight miRNA expression profiles and 6mer seed match with the eight miRNAs. We assumed that loads were significant if they had an absolute load greater than 2. For seed match, 1/0 denotes ≥1 seed matches and no seed match.

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Additional file 3:

Cooperativity between miRNAs in IC 1. The p-values (uncorrected) and q-values (corrected) for pairwise miRNA cooperativity in IC 1 are shown. 1/-1 denotes whether the individual miRNA has positive or negative loads in IC 1.

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Additional file 4:

Coefficients for the linear superposition of the ICs giving the miRNA expression profiles. R2 is the coefficient of determination.

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Additional file 5:

Genes regulated by Pdx-1 and/or IL-1β. 1/0 denotes regulation and no regulation based on text mining.

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Additional file 6:

Pathways significantly enriched for genes with high positive or low negative loads in the ICs. Sheet 1 shows KEGG pathways whereas sheet 2 shows MSigDB pathways. Only pathways with q-values < 0.05 (fdr corrected p-values) are highlighted.

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Additional file 7:

Expression of the eight miRNAs in α- versus β-cells. Ratio of basal ΔCT values for αTC1 versus βTC3 cells. The ratio is found for un-stimulated cells. Bars are standard deviations and asterisks denote: **: 0.01 > q > 0.001, ***: 0.001 > q > 0.

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Additional file 8:

Overall q-values for the miRNA expressions. FWER: family-wise error rate.

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