Biology is increasingly becoming an information-driven science. To harness the opportunities of the post-genomic era in furthering health sciences research and improving health care, there is an enormous demand for biologists who are trained in mathematics and computer science and can think quantitatively. However, current disciplinary graduate training programs are not designed to accommodate these rapid changes in the biological research perspective. This need serves as the motivation for the development of specialized graduate training programs that will train students at the interface between biology, engineering and computer science. To address this need, UCSD established an interdisciplinary Graduate Program in Bioinformatics in 2001 under the directorship of Dr. Shankar Subramaniam. In 2008, it was renamed Graduate Program in Bioinformatics and Systems Biology and reorganized with Drs. Pavel Pevzner and Alex Hoffmann taking on the directorship, and the continued guidance from Dr. Subramaniam and an active steering committee containing representative faculty from all five participating UCSD schools and academic divisions. The primary objectives of this renewal application of the Training Grant by the three co-PIs are to continue and expand this premier Graduate Program, support the highest quality students in their truly interdisciplinary training which blends biomedicine, computer science and engineering. Indeed in the course of their training Program students have contributed important discoveries and impactful advances in health sciences research. The Program will continue to offer a core curriculum and a host of electives that will prepare a student solve difficult problems in biomedical research. Research training begins with a set of research rotations in laboratories of faculty members, and continues through doctoral research work under the supervision of a Ph.D. advisor and co-advisor who provide complementary interdisciplinary expertise, as well as the doctoral thesis committee. The Program will continue to a recently established weekly Colloquium, the student Journal Club, and annual retreat. Given the extraordinary number and quality of applicants, the capacity and eagerness of the Program faculty to train the Program's students, and the institutional support for the Program, this application seeks to increase the number of trainee slots to 18. Following Training Grant support of Graduate students during their course work education and initial research training, all graduate students will be supported by their thesis advisors for the duration of their Ph.D. studies.