Pharmacogenomics is the study of how human genetic variation impacts drug response. It is one of the major promises of the genome project: that individual genetic information can be used to select drugs with maximum efficacy and minimal side effects. An understanding of pharmacogenomics requires dual understanding of the basics of genetics and genomics, as well as pharmacology. In this class, we will present students with the background to understand the current state and literature in pharmacogenomics, including the methods used in research and the current issues in discovery, implementation and regulation of pharmacogenomics.
Overview of the topics covered in the program:
- • Introduction to Pharmacogenomics
- • Pharmacology
- • Genomics
- • Population Genetics
- • Technologies, Tools, and Methods
- • Classic and Key Examples
- • Implementation and Challenges
- • Regulatory and Ethical Considerations
- • Data Mining in Pharmacogenomics
The summary below lists the course lecture modules and associated learning objectives. Each module consists of 1-4 videos presenting a self-contained set of ideas. Thus, the modules range from 10 to 40 minutes long and are presented by Professor Altman, and Dr. Whirl-Carrillo.
|1. Introduction to Pharmacogenomics||We introduce the course, and the basic concepts of pharmacogenomics, including some initial examples, and a review of the topics to be covered in class.|
|2. Pharmacology||Pharmacokinetics is how a drug is absorbed, distributed, metabolized and excreted (ADME). Pharmacodynamics is how the drug works (target and pathways). Genes implement both PK and PD.|
|3. Genomics||We discuss the basic concepts of genomics including how single nucleotide polymorphisms and other types of genetic variation are applied in pharmacogenomics.|
|4. Population genetics||This section covers genetic variation within populations and how genetic drift and selection are relevant to pharmacogenomics studies.|
|5. Technologies, Tools, and Methods||How do we discover the genes responsible for modulating a drug effect? Here we discuss candidate gene studies and genome-wide association studies.|
|6. Classic and Key Examples|
In this section we cover the cytochrome P450 gene family. This gene family produces a variety of enzymes responsible for the metabolism of several key drugs.
|7. Implementation and Challenges||As we move towards clinical implementation of PGx, what are the key challenges in terms of educating physicians, introducing PGx advice into their normal workflow, and measuring the effect of PGx on patient outcomes?|
|8. Regulatory and Ethical Considerations||We review how drugs are approved, and the special challenges presented by drugs which should only be used in a subpopulation of patients. How is the FDA approaching the approval of pharmacogenomics tests and therapeutics?|
|9. Data Mining in Pharmacogenomics||Many drug interactions are modulated by genes. We will discuss ways in which we can discover and use information about pharmacogenomics for drug interaction discovery and management.|
The AMIA 10x10 program with Stanford University consists of 10 weeks of online training. The course is presented by Prof. Altman, and Drs. Whirl Carrillo (PharmGKB) and Khuri (UCSF-Stanford CERSI). The delivery method is web-based video, which includes direct screen capture of slides along with video of the presenter. The course will be accessed through Stanford Canvas. Teaching Assistants (TAs) will be available.
The learning objectives of this course can be summarized as:
- • To understand the basic principles of pharmacology and genomics as they pertain to pharmacogenomics.
- • To understand the different considerations applying to genes involved in pharmacokinetics versus pharmacodynamics, and how this impacts the way that these genes are studied.
- • To understand the impact of emerging technologies, such as next generation sequencing on discovery and implementation of pharmacogenomics.
- • To understand several specific examples of important pharmacogenomics and their implementation in clinical practice.
- • To understand the available information resources about gene-drug interactions, and how they can be used in informatics projects.
- • To understand the issues and challenges of implementing pharmacogenomics in the clinic, and in regulating the use of pharmacogenomics by the FDA.
Reading assignments consist of chapters from the required textbook:
- • Principles of Pharmacogenetics and Pharmacogenomics
Russ B. Altman (Editor), David Flockhart (Editor), David B. Goldstein (Editor)
Cambridge University Press, 2012.
The website for the course is at: https://web.stanford.edu/group/canvas/discovery/
This 10x10 course offering, in partnership with the Stanford University will start on September 23, 2019 and end December 13, 2019. The registration deadline is September 23, 2019. Enrollments will be accepted after that date on a space-available basis.
Students are eligible for a 10x10 completion certificate and will also receive member rates to any AMIA meeting they attend in the 2019 calendar year.
Participants should have previous coursework in biology since the course will quickly move through many biology topics. We recommend participants have completed a modern, full-year, college-level biology sequence for biology majors, or equivalent.
Technical Comments: The topics covered in the course (summarized in the course curriculum) are presented in videotaped lectures with the instructors appearing onscreen during the lectures to explain or discuss ideas.