Sociology

Cell

Pattern recognition (psychology)

Biological system

Pooling

Biology

Gene

Algorithm

Normalization (sociology)

Deconvolution

Artificial intelligence

Database normalization

Anthropology

Computer science

Computational biology

Genetics

Genome biology

Normalization of single-cell RNA sequencing data is necessary to eliminate cell-specific biases prior to downstream analyses. However, this is not straightforward for noisy single-cell data where many counts are zero. We present a novel approach where expression values are summed across pools of cells, and the summed values are used for normalization. Pool-based size factors are then deconvolved to yield cell-based factors. Our deconvolution approach outperforms existing methods for accurate normalization of cell-specific biases in simulated data. Similar behavior is observed in real data, where deconvolution improves the relevance of results of downstream analyses.

Pooling across cells to normalize single-cell RNA sequencing data with many zero counts