a cf-mRNA transcriptome and whole-blood transcriptome from healthy subjects was decomposed using non-negative matrix factorization and tissue contribution estimated using public databases. cf-mRNA was sequenced from 24 normal donors and whole-blood RNA-Seq data from 19 healthy individuals reported in Nguyen et al. 20. Estimated contribution of the indicated cell types/tissues for each sample is shown. b Average values for each biofluid (24 cf-mRNA and 19 whole-blood samples) are shown using the same color code. c. RNA-Seq was performed in three paired plasma and whole-blood samples from healthy individuals. Levels of detectable cell-type-specific transcripts (Supplementary Table 5) were compared between cf-mRNA and whole blood for all three donors. Average fold change (cf-mRNA/whole blood) among the three individuals is represented (log scale) (two-sided Wilcoxon’s rank-sum test, U = 3.22). Red dots, neutrophil progenitor transcripts. Blue dots, mature neutrophil transcripts. Cell-type-specific genes were identified as explained in Methods. d RNA-Seq was performed in five paired plasma and buffy coat samples from healthy control individuals. Levels of mature and progenitor neutrophil transcripts detectable in plasma and matching buffy coat specimens were compared. Average fold change of these transcripts (plasma/buffy coat) in the five paired samples is shown (log scale). Two-sided Wilcoxon’s rank-sum test was performed (U = −3.40, p value = 0.00068). e, f Box-plot comparing the normalized levels (TPM) of the indicated transcripts in paired buffy coat and cf-mRNA samples measured by RNA-Seq (n = 5 samples, two-sided Wilcoxon’s rank-sum test), f PRTN3, U = −2.61, p value = 0.0090; e CXCR2, U = 2.61, p value = 0.0090. Center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, outliers. Source data for b–f are provided as a Source Data file g. Scatter plot comparing the levels in matching cf-mRNA (Y axis) and whole blood (X axis) of BM-specific genes (red dots) and peripheral blood-specific genes (blue dots), which form two distinct populations (p < 0.001, U = 18.58, two-sided Wilcoxon’s rank-sum test).