Computational screen to identify potential targets for immunotherapeutic identification and removal of senescence cells.

Abstract

To prioritize gene and protein candidates that may enable the selective identification and removal of senescent cells, we compared gene expression signatures from replicative senescent cells to transcriptomics and proteomics atlases of normal human tissues and cell types. RNA-seq samples from in vitro senescent cells (6 studies, 13 conditions) were analyzed for identifying targets at the gene and transcript levels that are highly expressed in senescent cells compared to their expression in normal human tissues and cell types. A gene set made of 301 genes called SenoRanger was established based on consensus analysis across studies and backgrounds. Of the identified senescence-associated targets, 29% of the genes in SenoRanger are also highly differentially expressed in aged tissues from GTEx. The SenoRanger gene set includes previously known as well as novel senescence-associated genes. Pathway analysis that connected the SenoRanger genes to their functional annotations confirms their potential role in several aging and senescence-related processes. Overall, SenoRanger provides solid hypotheses about potentially useful targets for identifying and removing senescence cells.