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New publication from Ben Humphreys’ lab | ATLAS-D2K Center


New publication from Ben Humphreys' lab

Feb 13, 2024

Here is another new publication from Ben Humphreys’ lab:

Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing

Authors: Nicolas Ledru, Parker C. Wilson, Yoshiharu Muto, Yasuhiro Yoshimura, Haojia Wu, Dian Li, Amish Asthana, Stefan G. Tullius, Sushrut S. Waikar, Giuseppe Orlando & Benjamin D. Humphreys

Journal: Nature Communications


Summary: 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.

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