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Table 1.

Study group demographics and sample number.

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Table 2.

Cytokine secretion by group and stimulation condition.

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Table 3.

Sizes of up-regulated and down-regulated differentially expressed gene signatures.

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Fig 1.

Egg-Induced differential gene expression.

Violin plots displaying egg-induced gene expression for the 15 genes that were most differentially expressed when comparing BER to AC subjects. Statistical analysis is indicated after each gene name.

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Table 4.

Top 30 up regulated and down-regulated genes in BER(EWvs.M) vs. AC(Ewvs.M) differential expression sorted by fold change.

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Fig 2.

Enrichment of differentially expressed gene signatures in Hallmark functional annotation categories.

Enrichment of selected DEG signatures (top 200 by FC from top 500 by p-values) in Hallmark functional categories, with the color intensity indicating–log10 of the BH adjusted p-value and the values are odds ratios from Fisher’s exact tests. The left 3 signatures indicate EW vs. M for each clinical group, while the right 3 signatures indicate the difference in differential (EW vs. M) gene expression between groups. The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). Hallmark categories with at least a single enrichment with BH adjusted p-value ≤ 0.05 (out of total of 50) are shown, clustered according to the similarity of the enrichment pattern. Colored text highlights significant associations with the matching DEG signature.

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Fig 3.

Enrichment of differentially expressed gene signatures for transcription factor targets.

Enrichment of the DEG signatures (top 200 by FC from top 500 by p-values) for transcriptional factor target gene sets, with Chip-X (ChIP-chip, ChIP-seq, ChIP-PET and DamID) derived ChEA set from human based experimental data in A), ChEA set from rodent based experimental data in B), and computationally predicted TRANSFACv.1 set in C). The color intensity indicates–log10 of the FDR adjusted p-values and the indicated values are odds ratios (Fisher’s exact test). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). The results are shown for only twelve (out of the total of 24 used in the analysis) DEG signatures, and only the TF target sets with at least a single enrichment with BH adjusted p-value ≤0.0001 for A) and B) and ≤0.05 for C), clustered according to the similarity of the enrichment pattern.

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Fig 4.

Differential expression of interferon response gene sets.

Differential expression of eleven genes from the HALLMARK_ INTERFERON_ALPHA_RESPONSE (including 7 genes also in INTERFERON_GAMMA_RESPONSE, on the left) gene sets overlapping with the DEG signatures (top 200 by FC from top 500 by p-values). Color intensity and values indicate the nominal significance of the differential expression analysis, with values corresponding to negative logarithm of p-values (included for p-values < 0.05). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue).

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Fig 5.

Immune Annotation analysis of the differentially expressed gene signatures.

The color intensity indicates the Immune Annotation Score and the values are the odds ratios from Fisher’s exact tests with BH adjusted p-value < 0.1 for the given test. A. Level 1 (Cells), B. Level 2 (Cell Subsets), C. Level 3 (Activation Status), D. Level 4 (TLR-activated myeloid cells). The color indicates whether the genes in the signature were up-regulated (red) or down-regulated (blue). The results are shown for twelve of the total 24 DEG signatures used in the analysis, and immune Annotation categories with at least a single category with BH adjusted p-value ≤ 0.1. Colored text highlights significant associations with the matching DEG signature. Inf = Infinite, all observations were within the subgroup.

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Fig 6.

Relationships between co-expression modules, cytokines, and differentially expressed gene signatures.

A) Association between gene modules and cytokine production, with the color intensity indicating p-value (–log10, BH-adjusted) from linear regression between the modules’ eigengenes and the level of cytokine, and color indicating the correlation direction (red = positive, blue = negative). B) Enrichment of the co-expression modules in differentially expressed gene signatures, with the color intensity indicating p-value (–log10, BH-adjusted) from Fisher’s exact test for modules’ enrichments in the DEG signatures, and color indicating whether the genes in the signature were up-regulated (red) or down-regulated (blue). Module size (number of genes) is indicated in parenthesis after the label; the color scale (p-value) is truncated at ±10 (max is 163).

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Fig 7.

Immune Annotation enrichment in five egg allergy-associated co-expression modules.

Enrichment results are shown for A) Level 1 immune cell types; B) Level 2 immune cell sub-types; C) Level 3 activation state of immune cell types; and D) Level 4 myeloid cell stimulation. The color intensity indicates the Immune Annotation Score and the values are the Fisher’s exact tests’ Odds Ratios for tests with BH adjusted p-value ≤ 0.10. Only categories with at least one significant result are included. Inf = Infinite, all observations were within the subgroup.

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