The cells in different conditions have the different biological response that suited to such conditions. Difference in involved gene expression in cell metabolism caused the distinctive answers. Differential Expression Analysis (DEA) make it possible to identify the different gene expression by methods and technologies such as microarray and high throughput sequencing of CDNA (RNA-Seq). RNA-Seq is one of the most applied techniques with numerous advantages versus microarray technique. This method is used to discover the new genes as splicing variants and differential expression analysis. More needs due to radical usage for applying suitable analysis tools have been sensed in recent years. More focus to DE in eukaryotes is reasoned significantly for developing analysis tools in this type of cells, while prokaryotic cells are applied in treating disease and industrial purposes. It have been discussed widely to DEA subjects in such cells whereas the finite number of analysis softwares are belong and usable for prokaryotic cells. In this article we introduce and compare the specifications for the prokaryotic tools for DEA. Some prokaryotic professional softwares and pipelines could be used for transcriptomic analysis of RNA-Seq such as SPARTA, Rockhopper, EDGE-pro and gene-counter. SPARTA is a bacterial workflow and it is limited to single end Illumina reads [1]. Rockhopper is a automatic software while it could be applied for two reference-based and de novo mode and it is capable of both single end read and paired end read style [2] whereas EDGE-pro which use aligner bowtie2 is depended to DESeq or EdgeR for analysis [3]. In return gene-counter have the usability for eukaryotes and prokaryotes. In addition for aligner and DEA, it allows for users to gain from the different statistical packages. Significant attention have been held in these tools to prokaryotic features that consist of overlap and lack of introns. Eukaryotic pipelines usually ignore overlaps, so this is the significant issue where bacterial genes have 15% overlap or higher. Lack of introns in prokaryotic cells is caused Algorithms that correspond to splicing detections have not the desired results on prokaryotic pipelines [4]. By considering the genomic differences in eukaryotic and prokaryotic cells the DEA must be perform with suitable softwares that chosen with these differences. In this article prokaryotic cells have been compared and investigated with proper softwares in order to make it easy for readers to select a convenient software.

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