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In Journal of computational biology : a journal of computational molecular cell biology

Dimensionality reduction is an important first step in the analysis of single-cell RNA-sequencing (scRNA-seq) data. In addition to enabling the visualization of the profiled cells, such representations are used by many downstream analyses methods ranging from pseudo-time reconstruction to clustering to alignment of scRNA-seq data from different experiments, platforms, and laboratories. Both supervised and unsupervised methods have been proposed to reduce the dimension of scRNA-seq. However, all methods to date are sensitive to batch effects. When batches correlate with cell types, as is often the case, their impact can lead to representations that are batch rather than cell-type specific. To overcome this, we developed a domain adversarial neural network model for learning a reduced dimension representation of scRNA-seq data. The adversarial model tries to simultaneously optimize two objectives. The first is the accuracy of cell-type assignment and the second is the inability to distinguish the batch (domain). We tested the method by using the resulting representation to align several different data sets. As we show, by overcoming batch effects our method was able to correctly separate cell types, improving on several prior methods suggested for this task. Analysis of the top features used by the network indicates that by taking the batch impact into account, the reduced representation is much better able to focus on key genes for each cell type.

Ge Songwei, Wang Haohan, Alavi Amir, Xing Eric, Bar-Joseph Ziv


batch effect removal, data integration, dimensionality reduction, domain adversarial training, single-cell RNA-seq