For the preservation of shorter fragment reads, barcode removal and adapter trimming need to be done. After read preprocessing, the alignment of reads to the human genome reference should be performed. Original EPIC-seq used hg19 but for better results, an updated version of human genome reference can be used. One should be careful about their aligner's options since some aligners can interfere with the inclusion of shorter reads paired with longer ones. For the deduplication, attached molecular customized barcodes should be exploited. These barcodes include endogenous and exogenous unique molecular identifiers (UMIs) and are handy for distinguishing Polymerase Chain Reaction (PCR) duplicates from real duplicates and hence for PCR duplicate cleansing. This portion is especially important for oncologic applications since the low mutation abundance can be suppressed by PCR duplicates.