Employing the AS as a bona fide transcriptomic reference. (A) Using RS and dGSE analyses to compare existing data sets to the AS. Left panel shows a graphical representation of the dGSE enrichment analyses from our own generated HSC transcriptome data compared with the AS. Right panel shows plots of RS (upper) and dGSE (lower) enrichment analyses of all individual studies that comprise the AS. Numbers refer to the studies shown on the right. (B) Searching for an AS using RS and dGSE analyses in independent data sets. Upper left panel shows a lack of enrichment for aging genes in an embryonic stem cell signature from Wong et al.³⁰  Upper right panel shows enrichment for the top 250 genes (sorted by FDR value) of Kim et al (K.K., A.M.-M and B.v.E, manuscript submitted December 2020). Lower right panel shows significant enrichment for an HSC AS among genes downregulated in “rejuvenated” HSCs from Maryanovich et al.¹⁸  Lower right panel shows significant enrichment for a HSC signature among differentially expressed genes in HSCs isolated from young DNMT3A/B knockout mice from Challen et al.²⁹  The right-most panels show combined RS and dGSE scores for each test set. (C) Single-cell AS scores. Separation of young (circles) and aged (triangles) single-cell transcriptomics and their respective AS score. From Grover scRNA-seq data (48 young and 68 aged cells), individual cells were separated by principal component 1 (PC1) (x-axis) and PC2 (y-axis) and color-coded according to their individual AS score. Left column displays only young cells; middle column shows just aged cells and right column shows both populations. Cells are colored score from low (blue) to high (yellow) AS scores. On the far-right panel, violin and boxplots demonstrate the overall AS score (y-axis) distribution of the young (gray) and aged (red) cells.