RT Journal Article SR Electronic T1 Transcriptional output, cell types densities and normalization in spatial transcriptomics JF bioRxiv FD Cold Spring Harbor Laboratory SP 503870 DO 10.1101/503870 A1 Saiselet, Manuel A1 Rodrigues-Vitória, Joël A1 Tourneur, Adrien A1 Craciun, Ligia A1 Spinette, Alex A1 Larsimont, Denis A1 Andry, Guy A1 Lundeberg, Joakim A1 Maenhaut, Carine A1 Detours, Vincent YR 2020 UL http://biorxiv.org/content/early/2020/03/27/503870.abstract AB Spatial transcriptomics measures mRNA at hundreds of 100 micrometer-diameter spots evenly spread across 6.5×6.9 mm2 histological slices. Gene expression within each spot is commonly normalized by total read counts. However we show that the transcriptional output of individual spots reflects the number of cells they contain, hence total read counts per spot reflect relevant biology. Although per-spot read-count normalization reveals important enrichment trends, it may heavily distort cell-type-related absolute local expression and conceal important biological information.