RT Journal Article SR Electronic T1 Concordance of MERFISH spatial transcriptomics with bulk and single-cell RNA sequencing JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202201701 DO 10.26508/lsa.202201701 VO 6 IS 1 A1 Jonathan Liu A1 Vanessa Tran A1 Venkata Naga Pranathi Vemuri A1 Ashley Byrne A1 Michael Borja A1 Yang Joon Kim A1 Snigdha Agarwal A1 Ruofan Wang A1 Kyle Awayan A1 Abhishek Murti A1 Aris Taychameekiatchai A1 Bruce Wang A1 George Emanuel A1 Jiang He A1 John Haliburton A1 Angela Oliveira Pisco A1 Norma F Neff YR 2023 UL https://www.life-science-alliance.org/content/6/1/e202201701.abstract AB Spatial transcriptomics extends single-cell RNA sequencing (scRNA-seq) by providing spatial context for cell type identification and analysis. Imaging-based spatial technologies such as multiplexed error-robust fluorescence in situ hybridization (MERFISH) can achieve single-cell resolution, directly mapping single-cell identities to spatial positions. MERFISH produces a different data type than scRNA-seq, and a technical comparison between the two modalities is necessary to ascertain how to best integrate them. We performed MERFISH on the mouse liver and kidney and compared the resulting bulk and single-cell RNA statistics with those from the Tabula Muris Senis cell atlas and from two Visium datasets. MERFISH quantitatively reproduced the bulk RNA-seq and scRNA-seq results with improvements in overall dropout rates and sensitivity. Finally, we found that MERFISH independently resolved distinct cell types and spatial structure in both the liver and kidney. Computational integration with the Tabula Muris Senis atlas did not enhance these results. We conclude that MERFISH provides a quantitatively comparable method for single-cell gene expression and can identify cell types without the need for computational integration with scRNA-seq atlases.