ZERO-INFLATED QUANTILE RANK-SCORE BASED TEST (ZIQRANK) WITH APPLICATION TO SCRNA-SEQ DIFFERENTIAL GENE EXPRESSION ANALYSIS.

Differential gene expression analysis based on scRNA-seq data is challenging due to two unique characteristics of scRNA-seq data. First, multimodality and other heterogeneity of the gene expression among different cell conditions lead to divergences in the tail events or crossings of the expression distributions. Second, scRNA-seq data generally have a considerable fraction of dropout events, causing zero inflation in the expression. To account for the first characteristic, existing parametric approaches targeting the mean difference in gene expression are limited, while quantile regression that examines various locations in the distribution will improve the power. However, the second characteristic, zero inflation, makes the traditional quantile regression invalid and underpowered. We propose a quantile-based test that handles the two characteristics, multimodality and zero inflation, simultaneously. The proposed quantile rank-score based test for differential distribution detection (ZIQRank) is derived under a two-part quantile regression model for zero-inflated outcomes. It comprises a test in logistic modeling for the zero counts and a collection of rank-score tests adjusting for zero inflation at multiple prespecified quantiles of the positive part. The testing decision is based on an aggregate result by combining the marginal