Loss of coordination between basic cellular processes in human aging.

Age-related loss of gene expression coordination has been reported for distinct cell types and may lead to impaired cellular function. Here we propose a method for quantifying age-related changes in transcriptional regulatory relationships between genes, based on a model learned from external data. We used this method to uncover age-related trends in gene-gene relationships across eight human tissues, which demonstrates that reduced co-expression may also result from coordinated transcriptional responses.

Regulatory network-based imputation of dropouts in single-cell RNA sequencing data.

Single-cell RNA sequencing (scRNA-seq) methods are typically unable to quantify the expression levels of all genes in a cell, creating a need for the computational prediction of missing values ('dropout imputation'). Most existing dropout imputation methods are limited in the sense that they exclusively use the scRNA-seq dataset at hand and do not exploit external gene-gene relationship information. Further, it is unknown if all genes equally benefit from imputation or which imputation method works best for a given gene.

PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells.

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target.