scHD4E: Novel ensemble learning-based differential expression analysis method for single-cell RNA-sequencing data

Abstract

Differential expression (DE) analysis between cell types for scRNA-seq data by capturing its complicated features is crucial. Recently, different methods have been developed for targeting the scRNA-seq data analysis based on different modeling frameworks, assumptions, strategies and test statistic in considering various data features. The scDEA is an ensemble learning-based DE analysis method developed recently, yielding p-values using Lancaster's combination, generated by 12 individual DE analysis methods, and producing more accurate and stable results than individual methods. The objective of our study is to propose a new ensemble learning-based DE analysis method, scHD4E, using top performers in only 4 separate methods. The top performer 4 methods have been selected through an evaluation process using six real scRNA-seq data sets. We conducted comprehensive experiments for five experimental data sets to evaluate our proposed method based on the sample size effects, batch effects, type I error control, gene ontology enrichment analysis, runtime, identified matched DE genes, and semantic similarity measurement between methods. We also perform similar analyses (except the last 3 terms) and compute performance measures like accuracy, F1 score, Mathew's correlation coefficient etc. for a simulated data set. The results show that scHD4E is performs better than all the individual and scDEA methods in all the above perspectives. We expect that scHD4E will serve the modern data scientists for detecting the DEGs in scRNA-seq data analysis. To implement our proposed method, a Github R package scHD4E and its shiny application has been developed, and available in the following links: https://github.com/bbiswas1989/scHD4E and https://github.com/bbiswas1989/scHD4E-Shiny.

Keywords: Differential expression; scDEA; scHD4E; scRNA-seq.