Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing.
Nat Commun
; 15(1): 1291, 2024 Feb 12.
Article
in En
| MEDLINE
| ID: mdl-38347009
ABSTRACT
Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes. Single nucleus joint RNA- and ATAC-seq sequencing offers an opportunity to study the gene regulatory networks underpinning these changes in order to identify key regulatory drivers. We develop a regularized regression approach to construct genome-wide parametric gene regulatory networks using multiomic datasets. We generate a single nucleus multiomic dataset from seven adult human kidney samples and apply our method to study drivers of a failed injury response associated with kidney disease. We demonstrate that our approach is a highly effective tool for predicting key cis- and trans-regulatory elements underpinning the healthy to failed repair transition and use it to identify NFAT5 as a driver of the maladaptive proximal tubule state.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Renal Insufficiency, Chronic
/
Multiomics
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: