This book constitutes the proceedings of the 12th International Symposium on Bioinformatics Research and Applications, ISBRA 2016, held in Minsk, Belarus, in June 2016. The 25 papers presented in this volume were carefully reviewed and selected from 77 submissions. They were organized in topical sections named: next generation sequencing data analysis; protein-protein interactions and networks; protein and RNA structure; phylogenetics; sequence analysis; and statistical methods.