Bioinformatics and Computational Biology (BCB) combine elements of computer science, information technology, mathematics, statistics, and biotechnology, providing the methodology and in silico solutions to mine biological data and processes, for knowledge discovery. In the era of molecular diagnostics, targeted drug design, translational medicine and Big Data for personalized medicine, computational methods for data analysis are essential tools for biochemistry, biology, biotechnology, pharmacology, biomedical and computer science, as well as mathematics and statistics. New areas are emerging, and relatively isolated fields are becoming current hot research areas in BCB, such as Artificial Intelligence, Quantitative Biology, Computational Vaccinology, Epidemiology and Infection Diffusion, Synthetic Biology, and Phenomics. The role of BCB in characterizing SARS-CoV-2 variants and facing the COVID-19 pandemic is just one example of how these tools can help us better prepare for such future events. This Encyclopedia comprises three sections, covering Methods, Topics, and Applications. The methodologies and algorithms underpinning BCB are described in the Methods section; Topics covers traditional areas such as phylogeny, as well as more recent areas such as translational bioinformatics, cheminformatics and environmental informatics; Applications provides guidance for commonly asked "how to" questions. Navigating the maze of confusing jargon and the plethora of software tools is often confronting for students and researchers alike. This comprehensive and unique resource provides up-to-date theory and application content to address molecular data analysis requirements, with precise definitions of terminology and lucid explanations by field experts. Revised and expanded, this new edition spans basics to cutting-edge methodologies, with chapters authored by leaders in the field Serves an audience with diverse backgrounds, combining elements of computer science, information technology, mathematics, statistics, and biotechnology, providing the methodology and in silico solutions to mine biological data and processes for knowledge discovery Provides succinct definitions of terms, possibly for the first time in some cases, an invaluable tool to navigate the complexity of the field New topics include areas such as Artificial Intelligence, Quantitative Biology, Computational Vaccinology, Epidemiology and Infection Diffusion, Synthetic Biology, and Phenomics Focused chapters highlight the knowledge and tools developed in response to the COVID-19 pandemic