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Here, we report the application of an entropy-enhanced frequency-domain analysis method to examine large-scale genomic data. This ensures superior coherency for qualitative and quantitative analysis. Different statistical methods are used to analyze large-scale data produced and attempts have been made to perform data mining. These efforts have been partially successful due to sequence gaps, noncoding and low complexity regions, inaccuracy, etc. In contrast, we report a novel robust method that is based on frequency-domain analysis. Our paradigm complements a number of far-reaching perceptions that new concepts emerge to comprehend complex large-scale genomic data under uncertainties.