Extended Data Fig. 7. Plasma ingress and frank blood define distinct peripheral CSF signatures.

(a) Derivation of a 20-protein plasma-ingress signature from plasma enrichment, liver specificity and association with the CSF-to-serum albumin quotient (QAlb), and a 10-protein frank-blood signature from bloody-versus-clean CSF contrasts and erythrocyte markers. (b) Human Protein Atlas (HPA) tissue-consensus RNA expression of plasma candidates across 36 tissues. Colour, log₁₀-transformed nTPM; marginal bars, mean expression. (c) Liver expression versus the highest non-liver tissue. Red triangles, selected plasma-ingress markers. (d) Concordance of liver-specificity τ and Gini indices across HPA proteins (Spearman ρ = 0.93). Inset, most liver-specific protein. (e) Cross-platform concordance of protein–QAlb correlations in Bader 2026 (timsTOF versus Astral; 1,637 shared proteins; Spearman ρ = 0.67). Red triangles, selected markers. (f) Random-effects meta-analysis of protein–QAlb correlations across Bader 2026, Schmid 2021 and Held 2024. Points, pooled Spearman ρ; bars, 95% CI. (g) Concordance of frank-blood differential abundance between pooled Bader 2026 erythrocyte-positive versus erythrocyte-negative CSF and Mikolajewicz 2022 bloody versus clean CSF (750 shared proteins; Spearman ρ = 0.19). Red triangles, selected markers; line and shading, linear fit and 95% CI. (h) Top pathway enrichments for each signature. Bars, −log₁₀ FDR from hypergeometric over-representation analysis. (i) Random-effects-pooled within-study correlations of plasma-ingress (blue) and frank-blood (red) scores with the 13 CSF MPs. Points and bars, pooled Spearman ρ and 95% CI.