Journal: bioRxiv

Article Title: Sex and Alternative Splicing in Disease: a meta-analytic approach to identify interactions

doi: 10.64898/2026.05.29.728908

Figure Lengend Snippet: Gene expression in control samples was compared between CD4+ and CD8+ samples (A) Proportion of all genes, immune genes and T1D genes that are differentially expressed between CD4+ and CD8+ control samples. T1D candidate genes and immune relevant genes are more likely to be differentially expressed between these cell types. (B) Annotated and detected exon and intron features for T1D candidate gene UBASH3A. From bottom to top i) The reference MANE transcript ii) all annotated features in Refseq/Ensembl iii) Exon/Intron features detected by long read sequencing in both cell types iii) Exon/Intron features detected in CD4+ RNA-seq samples (n=113) iv) Exon/Intron features detected in CD8+ RNA-seq samples (n=98). Exon Region 5 of UBASH3A is differentially detected between CD4+ and CD8+. (C) Proportion of all genes, immune genes and T1D genes with at least one differentially detected feature between CD4+ and CD8+samples. T1D genes are more likely to have differentially detected exon/intron features between CD4+ and CD8+ cells.

Article Snippet: ; Short read sequencing libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep kit (New England BioLabs) and sequenced by Macrogen.

Techniques: Gene Expression, Control, Sequencing, RNA Sequencing

Journal: bioRxiv

Article Title: Sex and Alternative Splicing in Disease: a meta-analytic approach to identify interactions

doi: 10.64898/2026.05.29.728908

Figure Lengend Snippet: A) Annotated and detected exon and intron patterns for T1D candidate gene RPAP2. From bottom to top i) The reference MANE transcript ii) all annotated features in either Refseq/Ensembl iii) Exon/Intron features detected by long read sequencing in both cell types iv) Exon/Intron features detected in CD4+ RNA-seq samples (n=113) Exon regions 1,4 and 7 are labelled. (B) – (D) Normalized expression level (log uq APN) of exon regions 1,4 and 7 stratified by sex and T1D status. Log UQ APN of 3 is shown with black dotted line across all plots. (E)-(G) Effect size of T1D on exon regions 1,4 and 7 stratified by sex in CD4+ RNA-seq samples. A positive effect size indicates that controls are more highly expressed than cases and a negative effect size indicates that cases are more highly expressed than controls for a given feature. Effect size of 0 is represented by the black dotted line. The upper and lower bounds of the 95% confidence interval for the effect size are shown for each feature.

Article Snippet: ; Short read sequencing libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep kit (New England BioLabs) and sequenced by Macrogen.

Techniques: Sequencing, RNA Sequencing, Expressing

Journal: bioRxiv

Article Title: Sex and Alternative Splicing in Disease: a meta-analytic approach to identify interactions

doi: 10.64898/2026.05.29.728908

Figure Lengend Snippet: (A) Annotated and detected exon and intron patterns for T1D candidate gene STRN4. From bottom to top i)The reference MANE transcript ii) all annotated features in either Refseq/Ensembl iii) Exon/Intron features detected by long read sequencing in both cell types iv) Exon/Intron features detected in CD4+ RNA-seq samples (n=113) (B) Normalized expression level (log_uq_apn) of CD4+ RNASeq samples for all features of the T1D candidate gene STRN4. There are differential rates of exon and intron feature inclusion across the length of the transcript (C) Effect size of T1D on all exon/intron features in STRN4 stratified by sex in CD4+ RNA-seq samples. The upper and lower bounds of the 95% confidence interval for the effect size are shown for each feature. Pvalue for the test of heterogeneity of female and male effect sizes and the Pvalue for the test of a moderator (sex) effect on the whole gene is shown. The test for heterogeneity is significant for females but not for males indicating that there is differential splicing between T1D cases and controls in female samples for the STRN4 gene. The test for moderator (sex) effect is significant indicating that there is an overall effect of sex on the gene.

Article Snippet: ; Short read sequencing libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep kit (New England BioLabs) and sequenced by Macrogen.

Techniques: Sequencing, RNA Sequencing, Expressing, RNA sequencing

Journal: bioRxiv

Article Title: Sex and Alternative Splicing in Disease: a meta-analytic approach to identify interactions

doi: 10.64898/2026.05.29.728908

Figure Lengend Snippet: A) Number and proportion of analyzable T1D genes with a 3-way interaction effect interaction of sex,splicing and T1D status for CD4+ and CD8+ samples. A higher proportion of T1D genes have a sex*splicing*T1D effect in CD4+ samples compared to CD8+ samples B) Annotated and detected exon patterns for T1D candidate gene BACH2. From bottom to top i) The reference MANE transcript ii) all annotated exons in Refseq/Ensembl iii) Exon features detected by long read sequencing in both cell types iii) Exon features detected in CD4+ RNA-seq samples (n=113) iv) Exon feautures detected in CD8+ RNA-seq samples (n=98). C) Effect size of T1D on all exonic features in BACH2 stratified by sex in CD4+ RNA-seq samples (top) and CD8+ RNA-seq samples (bottom). The upper and lower bounds of the 95% confidence interval for the effect size are shown for each feature. Pvalue for the test of heterogeneity of female and male effect sizes and the Pvalue for test of a moderator (sex) effect on the whole gene is shown. In CD4, the test for heterogeneity is significant for females but not for males indicating that there is differential splicing between T1D cases and controls in female samples for the BACH2 gene. The inverse effect is observed in CD8+ samples where we observe an effect of T1D on splicing in males but not females. Pvalue for the test of the 3-way interaction of sex, T1D and splicing differences is shown. This test of heterogeneity tests for the interaction of sex and splicing. Both CD4+ and CD8+ have a 3-way T1D*sex*splicing effect in the BACH2 gene.

Article Snippet: ; Short read sequencing libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep kit (New England BioLabs) and sequenced by Macrogen.

Techniques: Sequencing, RNA Sequencing