This book constitutes the proceedings of the 16th International Symposium on Bioinformatics Research and Applications, ISBRA 2020, held in Moscow, Russia, in December 2020. The 23 full papers and 18 short papers presented in this book were carefully reviewed and selected from 131 submissions. They were organized in topical sections named: genome analysis; systems biology; computational proteomics; machine and deep learning; and data analysis and methodology.