Extended Data Fig. 8 ∣. Cell-type deconvolution of bulk tissue RNA-seq data.

(a) After adjusting for cell type composition and repeating our EMMA and MASH models, similar numbers of genes per brain region pass our significance thresholds (LFSR < 0.2). (b) Standardized age effect estimates from analyses controlling and not controlling for cell-type composition are strongly positively correlated, but slopes < 1 in most brain regions suggest that some age effects identified in our bulk gene expression results are due to age-related changes in cell proportion. (c) The majority of aDEGs belonging to four clusters with pronounced age-associated directional changes (Fig. 1d) met our criteria (LFSR < 0.2) as aDEGs after controlling for heterogeneous tissue compositions using cell-type deconvolution (CD) analysis. Substantial fractions, however, did not, providing further evidence that some results at the bulk-tissue level are driven by age-related changes in cell proportion.