Personal Genomics for Bioinformaticians - Winter 2017

[course syllabus]

Announcements

• **The location of Monday's office hours (3pm-4:50pm) has changed to the CNCB building Room 127. Wednesday office hours will continue to be at CSE 4216 from 4-4:50pm.**

Course description

Genome-sequencing is quickly becoming a commodity, and more than a million people have already analyzed their own genomes through direct-to-consumer companies. This course provides an introduction to current bioinformatics techniques for analyzing and interpreting human genomes. We will learn how to interpret a single genome in the context of an entire population, based on the often quoted concept: interpreting one genome requires tens of thousands of genomes. Topics covered include an introduction to human medical and population genetics, human ancestry, finding and interpreting disease-causing variants, genome-wide association studies, genetic risk prediction, analyzing next generation sequencing data, and how to scale current genomics techniques to analyze hundreds of thousands of genomes. We will also discuss the social impact of the personal genomics revolution.

Schedule

Module	Date	Lecture	Homework
Introduction to personal genomics	01-10 (Th)	Introduction to your genome	ps1 out
What can I do with my genome?	01-12 (Th)	Basic population genetics	ps1 due, ps2 out
	01-17 (T)	Determining ancestry
	01-19 (Th)	Phasing and imputation
	01-24 (T)	Genetic Genealogy, Web 2.0 Genomics
	01-26 (Th)	Social impact of personal genomics (Guest lecture)	ps2 due
Complex traits	01-31 (T)	Introduction to GWAS	ps3 out
	02-02 (Th)	Risk prediction
	02-07 (T)	Missing heritability	project out
	02-09 (Th)	Scaling GWAS to millions of genomes	ps3 due
Next-gen sequencing and big data	02-14 (T)	Introduction to NGS	ps4 out
	02-16 (Th)	Short read alignment and variant calling	proposal due
	02-21 (T)	Long read sequencing technologies
	02-23 (Th)	Functional genomics - ChIPseq (Guest lecture)
	02-28 (T)	Storing, querying, visualization	ps4 due
Mutation hunting	03-02 (Th)	Introduction to genetic mapping	ps5 out
	03-07 (T)	Filtering and prioritizing variants
	03-09 (Th)	De novo mutations and constraint	ps5 due
	03-14 (T)	Interpreting non-coding variants
Final project	03-16 (Th)	Project presentations	project due

Resources for problem sets

• Getting started with comet
• Notes on using 23andme data for problem sets
• Problem set 1
• Problem set 2
• Problem set 3
• Problem set 4
• Problem set 5
• Final project

Class material

Lecture 1: Introduction to your genome

• CSE291 Lecture 1 Slides
• CSE291 Lecture 1 Notes

Lecture 2: Basic population genetics

• CSE291 Lecture 2 Slides
• CSE291 Lecture 2 Notes
• Recommended reading: Genome-wide detection and characterization of positive selection in human populations
  • Main text
  • Supplemental Material

Lecture 3: Determining ancestry

• CSE291 Lecture 3 Slides
• Recommended reading:
  • With genetic testing, I gave my parents the gift of divorce
  • DNA’s new ‘miracle’: How adoptees are using online registries to find their blood relatives

Lecture 4: Phasing and Imputation

• CSE291 Lecture 4 Slides
• CSE291 Tips for using XSEDE

Lecture 5: Mitochondria and Y chromosome analysis, Web 2.0 Genomics

• CSE291 Lecture 5 Slides - Part I
• CSE291 Lecture 5 Slides - Part II
• Recommended reading: Identifying Personal Genomes by Surname Inference
  • Main text
  • Supplemental Material

Lecture 6: Social impact of personal genomics

• CSE291 Lecture 6 Slides (Guest lecture by Cinnamon Bloss)

Lecture 7: Introduction to GWAS

• CSE291 Lecture 7 Slides

Lecture 8: Risk prediction

• CSE291 Lecture 8 Slides
• Example eye color prediction (on my genome)
• Recommended reading:
  • Human demographic history impacts genetic risk prediction across diverse populations [Supplemental Material]
  • Selection against variants in the genome associated with educational attainment

Lecture 9: Missing heritability

• CSE291 Lecture 9 Slides

Lecture 10: Scaling GWAS to millions of samples

• CSE291 Lecture 10 Slides
• Recommended reading:
  • Dissecting the genetics of complex traits using summary association statistics
  • A gene-based association method for mapping traits using reference transcriptome data

Lecture 11: Intro to NGS

• CSE291 Lecture 11 Slides

Lecture 12: Short read alignment and variant calling

• CSE291 Lecture 12 Slides (Part I)
• CSE291 Lecture 12 Slides (Part II)
• Recommended reading: lobSTR: A short tandem repeat profiler for personal genomes
  • Main text
  • Supplemental Material

Lecture 13: Long read sequencing technologies

• CSE291 Lecture 13 Slides

Lecture 14: Functional genomics - ChIP sequencing (Guest lecture Alon Goren)

• Recommended reading:
  • Charting histone modifications and the functional organization of mammalian genomes
  • (Webinar) Exploring genome-wide organization of chromatin structure by ChIP
• CSE291 Lecture 14 Slides

Lecture 15: Storing, querying, visualization (+RNAseq)

• CSE291 Lecture 15 Slides
• Links for visualization demos

Lecture 16: Intro to mutation hunting

• CSE291 Lecture 16 Slides
• Recommended reading:
  • Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome

Lecture 17: Filtering and prioritization

• CSE291 Lecture 17 Slides

Lecture 18: De novo mutations and constraint

• CSE291 Lecture 18 Slides
• Recommended reading: A framework for the interpretation of de novo mutation in human disease
  • Main text
  • Supplemental material

Lecture 19: Interpreting non-coding variants

• CSE291 Lecture 19 Slides
• Recommended reading: Machine learning begins to unlock non-coding variation

Lecture 20: Final Project Presentations