Cross-cohort optimal transport maps macrophage plasticity and routes to inflammation and fibrosis in human atherosclerosis

Scavenging and inflammatory macrophage states are the closest transcriptional pair across a human atherosclerosis atlas of 34,533 monocytes and macrophages, consistently across cohorts.

• Why it matters: Macrophage heterogeneity is known in plaques, but the specific identity remodeling routes linking states to inflammation and fibrosis are unclear.
• What they did: The authors built a computational framework using optimal transport, RNA velocity, and comparative program analysis across seven cohorts, with robustness checks and validation using paired RNA–protein and permutation tests in 18 patients.
• The result: Fibrotic association aligns with attenuation of the broader scavenging program, and symptomatic patients show a higher fraction of monocytes with strong inflammatory association (13.0 percentage points; unadjusted one-sided permutation p = 0.0017).

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