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- Title
Nuclei multiplexing with barcoded antibodies for single-nucleus genomics.
- Authors
Gaublomme, Jellert T.; Li, Bo; McCabe, Cristin; Knecht, Abigail; Yang, Yiming; Drokhlyansky, Eugene; Van Wittenberghe, Nicholas; Waldman, Julia; Dionne, Danielle; Nguyen, Lan; De Jager, Philip L.; Yeung, Bertrand; Zhao, Xinfang; Habib, Naomi; Rozenblatt-Rosen, Orit; Regev, Aviv
- Abstract
Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or are frozen, and opens the way to human genetics studies, clinical trials, and precise cell atlases of large organs. However, such applications are currently limited by batch effects, processing, and costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies to uniquely label nuclei from distinct samples. Comparing human brain cortex samples profiled with or without hashing antibodies, we demonstrate that nucleus hashing does not significantly alter recovered profiles. We develop DemuxEM, a computational tool that detects inter-sample multiplets and assigns singlets to their sample of origin, and validate its accuracy using sex-specific gene expression, species-mixing and natural genetic variation. Our approach will facilitate tissue atlases of isogenic model organisms or from multiple biopsies or longitudinal samples of one donor, and large-scale perturbation screens. Single-nucleus RNA-seq enables interrogation of complex tissues but is limited due to batch effects and processing costs. Here the authors use barcoded antibodies against the nuclear pore complex to label nuclei from distinct samples, and develop a computational tool to assign the sample of origin.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-10756-2