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Abstract

Single-cell Omic atlases are transforming biology and medicine, yet their demographic representativeness has not been systematically evaluated. We analyzed >13,500 samples from the Human Cell Atlas (HCA), Human Tumor Atlas Network (HTAN), and PsychAD Consortium. Benchmarking against global and US general and disease-prevalence data, we found a striking, pervasive European over-representation and under-representation of Asian and Latino individuals. Nearly 70% of HCA samples lacked ancestry annotation, and among annotated samples, Europeans were over-represented sixfold. PsychAD was nearly two-thirds European. HTAN tumors were 69% European, with several cancer types showing sex skews beyond expected incidence. These disparities highlight that current single-cell resources risk embedding inequities into AI foundational models, biomarker discovery, and therapeutic development. We contextualize these findings within the structural, economic, and regulatory, survey the growing ecosystem of diversity-focused initiatives, and provide an actionable, field-specific checklist to help research teams design single-cell studies whose benefits extend equitably across populations.

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