Biostatistics Seminar: Hanlee Ji
DATE: Tuesday, February 11th, 2014
TIME: 4:10pm (refreshments at 3:30pm, MSB 4110)
LOCATION: Mathematical Sciences Building 1147
SPEAKER: Hanlee Ji, Division of Oncology, Stanford University
TITLE: Deconvoluting Complex Genetic Mixtures with Next Generation DNA Sequencing: Clinical Relevance and Implications in Human Disease and Forensics
ABSTRACT:
Next generation DNA sequencing (NGS) approaches are widely used in studying human diseases and identifying causative genetic variants. Increasingly, NGS methods are used to define biologically relevant clonal mixtures, a frequently observed phenomenon in human disease and one that is frequently encountered in forensics. For example, an individual cancer is not homogeneous in its genetic composition, but instead, represents a mixture of different clonal subpopulations that have their own unique set of mutations and other genetic aberrations. Furthermore, the presence of normal tissue in a tumor can change the majority versus minority contribution of cancer mutations to the mixture. Similar genetic mixtures can be seen in certain viral infections with “quasispecies” with different genotypes in the same infected individual. Likewise, forensic analysis is oftentimes complicated by the presence of genetic mixtures arising from different individual contributors.
Within genetic mixtures unique clonal variants influence biology and changes in their representation can be indicators of evolutionary processes. This is frequently the case for drug resistance in cancer and viral infections. Thus, clonal genetic variation has major implications for the pathogenesis of human disease and is increasingly being tested as a longitudinal indicator of disease progression and treatment resistance. Complex genetic mixtures are a major challenge in analysis of forensic samples. To delineate the composition of genetic mixtures requires highly accurate methods and technologies. We have developed numerous technologies, experimental methods and approaches to improve the analysis of complex genetic mixtures. Our studies in cancer, viral progression and forensics have genetic, biological, clinical and societal significance.