Fig. 4: Decomposition benchmark in human dorsolateral prefrontal cortex tissue.

We randomly sampled 25% of the nuclei in the snRNA-seq data to accommodate the file size limit of the web-based implementation of CIBERSORTx at the time of writing. a Comparison of decomposition estimates from 628 individuals with estimates from 8 individuals with snRNA-seq data available. Each color represents a benchmarked method. Boxes indicate the quartiles of the estimated proportions with whiskers extending 1.5 times the interquartile range. Points are individual samples that are represented by the boxplot. b, c Violin plots depicting association of decomposition estimates aggregated into major cell types with measured phenotypes in 628 individuals. Reported ‘rho’ corresponds to Spearman correlation and p-values indicate the significance of these correlations, with an asterisk denoting both an expected effect direction and significance after correction for covariates. Examples shown are for the most abundant (neurons) and least abundant (microglia) populations detected in the snRNA-seq data. Significance of associations reported in Supplementary Table 2. b Neuronal degeneration has been observed in patients diagnosed with Alzheimer’s disease (AD). Cognitive diagnostic category measures a physician’s diagnosis of cognitive impairment (CI), with 0 indicating no CI and 4 indicating a confident AD diagnosis. We expected a negative correlation between neuron proportion and cognitive diagnostic category. c Microglia proportion has been observed to positively correlate with increased severity of AD symptoms, such as neurofibrillary tangles. Braak stage provides a semiquantitative measure of tangle severity, so we expected an overall positive correlation between microglia proportion and Braak stage. In addition, a decrease in microglia abundance has been previously reported at Braak stages 5 through 6 in AD patients. Only Bisque produced estimates with a significant positive association (p = 0.001) after correcting for sex, age, and age-squared in a linear regression model. Source data are provided as a Source Data file.