We have tackled the SARS-CoV-2 pandemic, but the lives lost were tragic. Our project delves into using bioinformatics tools to analyze mutations in the SARS-CoV-2 genome. Employed tools include IGV, SAMtools, BCFtools, Minimap, NCBI EDirect, AWK, and Jmol. IGV aids in visually inspecting genomic data for mutation identification. SAMtools and BCFtools process sequencing data to identify mutations from alignment (SAM/BAM) and variant call format (VCF) files. Minimap aligns SARS-CoV-2 sequences to a reference genome for mutation detection. NCBI EDirect retrieves SARS-CoV-2 sequences for mutation analysis. AWK filters and manipulates mutation data. Jmol visualizes the three-dimensional structure of SARS-CoV-2 spike proteins, aiding in understanding mutation implications. Integrating these tools enables comprehensive mutation analyses, offering insights into viral evolution and impacts on disease strategies. All files from this chapter are available from the book’s GitHub repository at CompBiol3/23_SARS-CoV-2 .