AbstractRNA-seq has matured and become an important tool for studying RNA biology. Here we compared two RNA-seq (MGI DNBSEQ and Illumina NextSeq 500) and two microarray platforms (GeneChip Human Transcriptome Array 2.0 and Illumina Expression BeadChip) in healthy individuals administered recombinant human erythropoietin for transcriptome-wide quantification of differential gene expression. The results show that total RNA DNB-seq generated a multitude of target genes compared to other platforms. Pathway enrichment analyses revealed genes correlate to not only erythropoiesis and oxygen transport but also a wide range of other functions, such as tissue protection and immune regulation. This study provides a knowledge base of genes relevant to EPO biology through cross-platform comparisons and validation.