10x10 with Stanford: Course Description

Curriculum and Competencies

Pharmacogenomics

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 would 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.

The learning objectives of this course can be summarized as:

1. To understand the basic principles of pharmacology and genomics as they pertain to pharmacogenomics.

2. To understand the different considerations applying to genes involved in pharmacokinetics versus pharmacodynamics, and how this impacts the way that these genes are studied.

3. To understand the impact of emerging technologies, such as next generation sequencing on discovery and implementation of pharmacogenomics.

4. To understand several specific examples of important pharmacogenomics, in order to see how the theoretical content of the course manifests in practice.

5. To understand the available information resources about gene-drug interactions, and how they can be used in informatics projects.

6. To understand the challenges of implementing pharmacogenomics in the clinic, and in regulating the use of pharmacogenomics by the FDA.

Overview of the topics covered in the program:

Outline
Pharmacology, PK, PD
ADRs, TPMT, Statins
SNPs, LD, Genotyping, GWAS
Candidate Gene and Pathway Approaches, Warfarin
Whole Genome Sequencing, Exome Sequencing
Rare Variant Interpretation
Introduction to PharmGKB
Databases and Informatics for Pharmacogenomics
Gene Expression and Drug Response: mRNA, NCI60, cMAP
Gene Expression and Drug Response: cMAP Applications and eQTLs
Translational Research in Drug-Drug Interactions
FDA
PGx Implementation Issues
Mining Clinical Data from the FDA AERS

Prerequisite

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 below) are presented in videotaped lectures. These lectures were initially presented live in the winter of 2012 during the first offering of the class. After the class was over, the instructors taped a second version of the lectures using powerpoints and a tablet that allows the instructors to draw and markup the powerpoint slides during the lecture. In addition, the instructors sometimes appear onscreen during the lectures to explain or discuss ideas. The individual classes were originally approximately 1 hour long, and so they have been divided into smaller modules so that independent users can complete smaller pieces of the class conveniently when time is available.

Complete Curriculum

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, graduate teaching assistants, and professional staff from PharmGKB.

1. Outline of the Course	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, PK, PD.	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. Adverse drug reactions, TPMT, Statins	Adverse drug reactions can result from genetics. Two examples are provided, including 6-mercaptopurine and mutations in the thiopurinemethyltransferase gene, and statins and a variation in SLC01B1 gene.
4. SNPs, LD, Genotyping, GWAS.	Genome wide association studies (GWAS) are based on the availability of genome-wide measurement of single nucleotide polymorphisms (SNPs), and form the basis for many PGx associations discovered in the last several years. Linkage disequilibrium is a key concept to understand why GWAS studies work.
5. Candidate Gene and Pathway Approaches, Warfarin.	How do we discover the genes responsible for modulating a drug effect? We discuss candidate gene approaches where we have some idea about how the drug works, including when the pathway of action is known. We use warfarin as an in-depth example of pharmacogenomics where pathways for both PK and PD are understood.
6. Whole Genome Sequencing, Exome Sequencing	Recent progress in sequencing now allows not just interrogating 1 million SNPs in the genome, but measuring all 6 billion bases. We will discuss how these technologies work and what are their current strengths/weaknesses.
7. Rare Variant Interpretation	Many genetic variations are not seen abundantly in the population, but are rare-unique to an individual or a small group of individuals (a family or isolated population). How do we analyze these variants in the context of drug response if we are unable to collect statistics because there are a limited number of patients?
8. Introduction to PharmGKB.	PharmGKB is the premier online repository of knowledge about pharmacogenomics, and so understanding its content is critical for ongoing interest in PGx.
9. Databases and Informatics for Pharmacogenomics	This lecture reviews other important data sources that form an infrastructure that relates genes to drugs and their molecular pathways.
10. Gene Expression and Drug Response: mRNA, NCI60, cMAP.	Drugs can impact the expression of genes in different cell types. These lectures discuss some existing data sets of gene expression changes in response to drugs, and the biology of how these effects occur. They also discuss the concept of an "expression quantitative trait locus" or eQTL which are gaining substantial interest.
11. Translational Research in Drug-Drug Interactions.	Many drug-drug interactions are modulated by genes (for example, if both drugs are metabolized by the same gene thus interact with each other). We will discuss ways in which we can discover and use information about pharmacogenomics for drug-drug interaction discovery and management.
12. FDA	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?
13. PGx Implementation Issues.	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?

Logistics

The AMIA 10x10 program with Stanford University consists of 10 weeks of online training. The course is presented by Prof. Altman, professional staff from PharmGKB, and graduate teaching assistants. The delivery method is web-based video, which includes direct screen capture of slides with tablet annotations along with video of the presenter. The course will have an accompanying website and TAs. The course director, Prof. Altman, will conduct two live Question and Answer sessions by video teleconference during the course for the AMIA 10x10 participants.

These 2 live "webinars" are currently scheduled for TBD.

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:
http://helix-web.stanford.edu/bmi224/index.php?n=Site.Lectures

Schedule

This 10x10 course offering, in partnership with the Stanford University will start on September 23, 2013 and end December 13, 2013. The registration deadline is September 23, 2013. Enrollments will be accepted after that date on a space-available basis.

Students will receive a complimentary membership to AMIA for the 2014 calendar year (a $300 value) which is good from Jan. 1st to Dec. 31st and includes a subscription to JAMIA. Students are also eligible for a 10x10 completion certificate.

Sun	Mon	Tue	Wed	Thu	Fri	Sat
	1	2	3	4	5	6
7	8	9	10	11	12	13
14	15	16	17	18	19	20
21	22	23	24	25	26	27
28	29	30	31

Search

Member Login