4.7 Article

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

Journal

AGING CELL
Volume 22, Issue 6, Pages -

Publisher

WILEY
DOI: 10.1111/acel.13809

Keywords

antibody drug conjugates; bioinforatics; biomarkers; CAR T-cell therapy; neoantigens; omics integration

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To identify potential targets for selective identification and removal of senescent cells, gene expression signatures of senescent cells were compared to normal human tissues and cell types. A gene set called SenoRanger, composed of 301 genes, was established based on consensus analysis. Pathway analysis confirmed the potential role of SenoRanger genes in aging and senescence-related processes. Overall, SenoRanger provides solid hypotheses for identifying and removing senescent cells.
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.

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