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<i>Salmonella</i> spp. and <i>Escherichia</i><i>coli</i> (<i>E. coli</i>) are two of the deadliest foodborne pathogens in the US. Genes involved in antimicrobial resistance, virulence, and stress response, enable these pathogens to increase their pathogenicity. This study aims to examine the genes detected in both outbreak and non-outbreak <i>Salmonella</i> spp. and <i>E. coli</i> by analyzing the data from the National Centre for Biotechnology Information (NCBI) Pathogen Detection Isolates Browser database. A multivariate statistical analysis was conducted on the genes detected in isolates of outbreak <i>Salmonella</i> spp., non-outbreak <i>Salmonella</i> spp., outbreak <i>E. coli</i>, and non-outbreak <i>E. coli</i>. The genes from the data were projected onto a two-dimensional space through principal component analysis. Hierarchical clustering was then used to quantify the relationship between the genes in the dataset. Most of the outlier genes identified in <i>E. coli</i> isolates are virulence genes, while outlier genes identified in <i>Salmonella</i> spp. are mainly involved in stress response. Gene <i>epeA</i>, which encodes a high-molecular-weight serine protease autotransporter of Enterobacteriaceae (SPATE) protein, along with <i>subA</i> and <i>subB</i> that encode cytotoxic activity, may contribute to the pathogenesis of outbreak <i>E. coli</i>. The <i>iro</i> operon and <i>ars</i> operon may play a role in the ecological success of the epidemic clones of <i>Salmonella</i> spp. Concurrent relationships between <i>esp</i> and <i>ter</i> operons in <i>E. coli</i> and <i>pco</i> and <i>sil</i> operons in <i>Salmonella</i> spp. are found. Stress-response genes (<i>asr</i>, <i>golT</i>, <i>golS</i>), virulence gene (<i>sinH</i>), and antimicrobial resistance genes (<i>mdsA</i> and <i>mdsB</i>) in <i>Salmonella</i> spp. also show a concurrent relationship. All these findings provide helpful information for experiment design to combat outbreaks of <i>E. coli</i> and <i>Salmonella</i> spp.