The landscape of allele-specific expression in human kidneys
Onuchic-Whitford, A. C.; Sung, J.; Sakkas, E. D.; McNulty, M. T.; O'Connor, C. L.; Greenberg, A.; Yoon, J. G.; Badina, S.; the Nephrotic Syndrome Study Network (NEPTUNE), ; Mariani, L. H.; Bitzer, M.; Sampson, M. G.; Lee, D.
Show abstract
Allele-specific expression (ASE), the preferential expression of one gene copy, is a key mechanism of genomic regulation. However, its role in human kidney disease remains poorly understood. In this study, we generated a high-quality, genome-wide ASE map using paired whole-genome sequencing and RNA-seq from microdissected glomerular (GLOM) and tubulointerstitial (TUBE) compartments of patients with proteinuric kidney disease. We showed that the majority of common ASE events were deterministic and sequence-mediated. We also found that diseased kidneys exhibited significantly more ASE in GLOM than TUBE, compared to controls. Unexpectedly, higher ASE in GLOM than TUBE was significantly associated with improved kidney disease outcomes in the disease cohort. Differential gene expression analysis suggested this was the result of an active, protective transcriptional response, including ribosome and ATP synthesis upregulation, rather than pathogenic dysregulation. Our work reveals glomerular ASE as a marker of adaptive transcriptional activity in proteinuric kidney disease.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Common genetic variation associated with Mendelian disease severity revealed through cryptic phenotype analysis 95%
- A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types. 95%
- The chromatin landscape of healthy and injured cell types in the human kidney 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury 96%
- Spatial profiling of the interplay between cell type- and vision-dependent transcriptomic programs in the visual cortex 96%
- Large scale functional screen identifies genetic variants with splicing effects in modern and archaic humans 96%
Similar papers in this journal
- Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control 96%
- CpG island turnover events predict evolutionary changes in enhancer activity 96%
- Accurate variant effect estimation in FACS-based deep mutational scanning data with Lilace 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.