Fig. 2: Distinct temporal patterns across selected islet autoimmunity associated genes and immune cell types. | Nature Communications

Fig. 2: Distinct temporal patterns across selected islet autoimmunity associated genes and immune cell types.

From: Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection

Fig. 2

a Conditional logistic regression analysis for differentially expressed genes between case and control children in different time points prior to IAb seroconversion. Associated p-values are indicated by the dot size and odds ratios (OR) by shades of red (>1, positively associated to islet autoimmunity NCC1, implying a higher risk for higher gene expression) and blue (<1, negatively associated to islet autoimmunity NCC1, which can be inferred as the higher gene expression being protective). P-values are unadjusted due to the nested case-control setting. b GSTM1 gene dosage effect in the full islet autoimmunity NCC1 cohort. Genotype is indicated with color: +/+ is for diploid, +/− for hemizygous deletion, and −/− for homozygous deletion. c Line plots covering 0-12 months prior to seroconversion showing the mean temporal differences in islet autoimmunity NCC1 cases and controls as illustrated by representative genes, selected based on known biological function, ZBED6 (full islet autoimmunity NCC1), GSTM1 (GADA-first) and FABP5 (IAA-first), with error bar showing the standard error of the mean (±sem) and highlighting the significant p-values derived from conditional logistic regression analysis (Supplementary Data 4). Temporal expression patterns for other genes are shown in Supplementary Figs. 5–7 and their detailed statistics, including log fold change and adjusted p-value are listed in the Supplementary Data 4. d Conditional logistic regression analysis identifies distinct immune cell type profiles for the full islet autoimmunity NCC1, GADA-first, and IAA-first seroconversion sets. IAA-first is shown to have more aberrant cell type profiles. The dot size and color have the same meaning as in a. e Using likelihood ratio test and as shown with ZBED6 (full islet autoimmunity NCC1), GSTM1 (GADA-first) and FABP5 (IAA-first) models, discrimination performances were consistently improved with the inclusion of gene, hla, SNPs and virus. Other putative temporal markers are shown in Supplementary Data 8 and Supplementary Fig. 12.

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