PT - JOURNAL ARTICLE AU - Booeshaghi, A. Sina AU - Hallgrímsdóttir, Ingileif B. AU - Gálvez-Merchán, Ángel AU - Pachter, Lior TI - Depth normalization for single-cell genomics count data AID - 10.1101/2022.05.06.490859 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.05.06.490859 4099 - http://biorxiv.org/content/early/2022/05/06/2022.05.06.490859.short 4100 - http://biorxiv.org/content/early/2022/05/06/2022.05.06.490859.full AB - Single-cell genomics analysis requires normalization of feature counts that stabilizes variance while accounting for variable cell sequencing depth. We discuss some of the trade-offs present with current widely used methods, and analyze their performance on 526 single-cell RNA-seq datasets. The results lead us to recommend proportional fitting prior to log transformation followed by an additional proportional fitting.Competing Interest StatementThe authors have declared no competing interest.