Identification of differentially expressed genes has been a high priority task of downstream analyses to further advances in biomedical research. Investigators have been faced with an array of issues in dealing with more complicated experiments and metadata, including batch effects, normalization, temporal dynamics (temporally differential expression), and isoform diversity (isoform-level quantification and differential splicing events). To date, there are currently no standard approaches to precisely and efficiently analyze these moderate or large-scale experimental designs, especially with combined metadata. In this report, we propose comprehensive analytical pipelines to precisely characterize temporal dynamics in differential expression of genes and other genomic features, i.e., the variability of transcripts, isoforms and exons, by controlling batch effects and other nuisance factors that could have significant confounding effects on the main effects of interest in comparative models and may result in misleading interpretations.