Plate IV.5 · Publications
A Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease
Preprint in bioRxiv, 25 September 2026.
Abstract
Blood provides an accessible window into human health, yet the absence of a peripheral blood mononuclear cells (PBMCs) reference with standardized immune cell annotations has constrained comparisons between single-cell RNA sequencing (scRNAseq) studies. Here, we present HARP (H uman Cell A tlas R eference for P BMCs), an integrated atlas of ∼9 million PBMCs from >2,600 donors across 15 studies spanning four continents, encompassing diverse populations, neonates to 97 years, across health and diverse immune-related diseases. We developed optimized integration workflows, including novel label-free metrics to assess integration quality, and generated community-driven consensus annotations for 192 immune cell subsets, identifying rare populations representing as few as 0.004% of PBMCs. HARP reveals coordinated cellular modules associated with age, sex, and disease, identifies female-biased interferon and inflammatory gene programs and their perturbation by COVID-19, and uncovers a novel sexual dimorphism in prostaglandin signaling. Finally, we introduce scTiger, a hierarchical label-transfer framework that accurately projects these 192 cell annotations onto ∼18 million additional PBMCs, providing a robust and transferable reference for harmonizing future PBMC studies. HARP provides a high-resolution community-driven reference atlas for PBMC annotation and analysis, as a basis for emerging clinical applications of single-cell genomics.
Cite
@misc{cujba2026community,
title = {{A Community-Driven Single-Cell PBMC Reference Integrating Landmark Datasets Spanning Health and Disease}},
author = {Cujba, Ana-Maria and Aguilar-Fernandez, Sergio and Antoinette, Adrien and Said, Wamia and Mueller, Michaela F. and Kock, Kian Hong and Nestor, Jacquelyn and Sonthalia, Radhika and Buyamin, Eliora V. and Rawat, Pragya and Predeus, Alexander and Kretschmer, Lorenz and Fei, Lijiang and Slowikowski, Kamil and Sen, Pritha and Cosgriff, Christopher V. and MGH COVID-19 Collection \& Processing Team and Dufva, Olli and Askari, Mohamad and Kimler, Kyle and Futey, Mary and Zucchi, Ida and Chatzigeorgiou, Arsenios and Nejad, Parisa and Jin, Liying and Bowen, Blake and Yang, Andrian and Lindeboom, Rik G. H. and Normand, Rachelly and Megas, Stathis and Ando, Yoshinari and Chatterjee, Ankita and Park, Jong-Eun and Majumder, Partha P. and Matangkasombut, Ponpan and Charoensawan, Varodom and Shin, Jay W. and Park, Woong-Yang and Asian Immune Diversity Atlas (AIDA) Network and Sansom, Stephen and Göttgens, Berthold and Powell, Joseph E. and Bod, Lloyd and Heyn, Holger and Theis, Fabian J. and Teichmann, Sarah A. and Luecken, Malte D. and Prabhakar, Shyam and Villani, Alexandra-Chloé and Reynolds, Gary},
howpublished = {bioRxiv},
publisher = {openRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.749940},
url = {https://doi.org/10.64898/2026.09.21.749940},
note = {Preprint}
}