- Big biomedical data has grown exponentially during the last decades, as well as the applications that demand the understanding and discovery of the knowledge encoded in available big data. In order to address these requirements while scaling up to the dominant dimensions of big biomedical data –volume, variety, and veracity– novel data integration techniques need to be defined. In this paper, we devise a knowledge-driven approach that relies on Semantic Web technologies such as ontologies, mapping languages, linked data, to generate a knowledge graph that integrates big data. Furthermore, query processing and knowledge discovery methods are implemented on top of the knowledge graph for enabling exploration and pattern uncovering. We report on the results of applying the proposed knowledge-driven approach in the EU funded project iASiS (http://project-iasis.eu/). in order to transform big data into actionable knowledge, paying thus the way for precision medicine and health policy making.