Dramatic advances in experimental technology and computational analysis are fundamentally transforming the basic nature and goal of biological research. The emergence of new frontiers in biology, such as evolutionary genomics and systems biology is demanding new methodologies that can confront quantitative issues of substantial computational and mathematical sophistication. In this course we will discuss classical approaches and latest methodological advances in the context of the following biological problems: 1) Computational genomics, focusing on gene finding, motifs detection and sequence evolution.2) Analysis of high throughput biological data, such as gene expression data, focusing on issues ranging from data acquisition to pattern recognition and classification. 3) Molecular and regulatory evolution, focusing on phylogene tic inference and regulatory network evolution, and 4) Systems biology, concerning how to combine sequence, expression and other biological data sources to infer the structure and function of different systems in the cell. From the computational side this course focuses on modern machine learning methodologies for computational problems in molecular biology and genetics, including probabilistic modeling, inference and learning algorithms, pattern recognition, data integration, time series analysis, active learning, etc.