Differential gene expression of retrotransposons (LTR and non-LTR) in peripheral blood leukocytes of people with gout

Figures

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  Fig. 1. Overview of the reproducibility‑based filtering strategy used to derive a robust set of differentially expressed HERVs. Peripheral blood leukocytes from people with gout and healthy controls were analyzed in two independent RNA‑seq experiments. Differential expression of HERV loci was assessed separately in each dataset using identical thresholds (adjusted p-value < 0.05 and |log₂ fold change| > 3). HERVs with consistent differential expression across both experiments were retained, resulting in a conservative set of 238 reproducibly altered HERVs used for downstream analyses

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  Fig. 2. Heatmap showing the differential expression of 238 HERVs found across all samples. Columns are sample id and annotated sample type with gout (green) and healthy (orange), gender status with male (blue) and female (pink). Rows are HERVs from Telescope. Values in heatmap plot are CPM of each category and samples, and the color map is from blue (min) to red (max)

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  Fig. 3. Another cohort of samples from people with gout and healthy individuals was used to validate the previous findings. Blood samples from this group of people with gout were collected during both the acute and chronic phases. Seven HERVs were identified that not only distinguish people with gout from healthy individuals but also differentiate between the acute phase and the chronic phase (lasting weeks to months) of gout

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  Fig. 4. GSVA analysis of the 11 HERV-related host gene panels. Heatmap showing all pathway heatmap quantified by GSVA. Red represents high enrichment, and blue indicates the opposite

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  Fig. 5. Heatmap showing the differential expression 49 non-LTR found across all samples. Columns are sample id and annotated sample type with gout (green) and healthy (orange). Rows are non-LTR from TEspeX. Values in heatmap plot are CPM of each category and samples, and the color map is from blue (min) to red (max)

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  Fig. 6. Eight types of immune cells exhibited differential enrichment between people with gout and healthy individuals: (A) immune cells that were elevated in people with gout compared to healthy individuals, and (B) immune cells that were reduced in people with gout compared to healthy individuals

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  Fig. 7. Venn diagrams illustrating HERVs with higher or lower expression levels following treatment with uric acid or monosodium urate in (A) HEK293 cells and (B) THP-1 cells. Shared and treatment-specific HERVs are shown to highlight common and distinct expression patterns between the two conditions

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  Fig. 8. Venn diagrams illustrating non LTR retrotransposons with higher or lower expression levels following treatment with uric acid or monosodium urate in (A) HEK293 cells and (B) THP 1 cells. Overlapping and unique elements indicate common and condition specific expression responses