SUMMARY: Supercoiling imposes stress on a DNA molecule that can drive susceptible sequences into alternative non-B form structures. This phenomenon occurs frequently in vivo and has been implicated in biological processes, such as replication, transcription, recombination and translocation. SIST is a software package that analyzes sequence-dependent structural transitions in kilobase length superhelical DNA molecules. The numerical algorithms in SIST are based on a statistical mechanical model that calculates the equilibrium probability of transition for each base pair in the domain. They are extensions of the original stress-induced duplex destabilization (SIDD) method, which analyzes stress-driven DNA strand separation. SIST also includes algorithms to analyze B-Z transitions and cruciform extrusion. The SIST pipeline has an option to use the DZCBtrans algorithm, which analyzes the competition among these three transitions within a superhelical domain. AVAILABILITY AND IMPLEMENTATION: The package and additional documentation are freely available at https://bitbucket.org/benhamlab/sist_codes. CONTACT: [email protected].