1 of 22

Genome Analysis Module:�Course Introduction

Dr. Phillip Richmond�UBC MSc Genetic Counselling�October 31st, 2022

2 of 22

Today’s Outline (October 31st)

  1. Who is Phil Richmond?
  2. Course overview
  3. Whole genome sequencing in the diagnosis of rare genetic disorders
  4. Logging in to the cluster
  5. Assigning patient cases
  6. Install of necessary software

3 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

4 of 22

Happy Halloween!

Billy Butcher, the Boys.

NSFW trailer -

https://www.youtube.com/watch?v=5SKP1_F7ReE

5 of 22

Teacher Bio

Dr. Phillip Richmond

PhD in Bioinformatics (October 2020), Wasserman Lab, UBC

Staff Scientist, PHSA, BCCHR, Precision Health Initiative

Website: www.philliprichmond.com

Twitter: @Phil_A_Richmond

Research:�Maximizing the Utility of Whole Genome Sequencing in the Diagnosis of Rare Genetic Disorders�

Previous work in Genomics: Genomic Contributions to Ethanol Sensitivity in Mice, Polyploid Evolution in Yeast, Brewing Yeast Genomics, Cancer Cell Epigenetics, Addiction Predisposition

Also loves teaching genomics, and my dog Sherlock Holmes.

6 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

7 of 22

Goal of the course

To get hands-on experience using whole genome sequencing in the diagnosis of rare genetic disorders.

8 of 22

How are we going to do it?

During this course, you will identify as a genome analyst.

Each of you will have a case to work on. All of the cases are different.

9 of 22

How are we going to do it?

During this course, you will identify as a genome analyst.

Each of you will have a case to work on. All of the cases are different.

Throughout the course, we will slowly build your toolkit with the ability to process, visualize, and interpret whole genome sequencing data.

The course will end with a presentation of the case to your peers with your proposed candidate variant.

https://www.clinicalpathwaysresearch.com/blog/2014/06/09/rbm-round-table-discussion

10 of 22

Course Syllabus

11 of 22

Accessing Course Content

12 of 22

How to keep up

With this class size we will not leave anyone behind!

You should work together!

Ask lots of questions, no question is “dumb”!

Celebrate the little wins!

For some sessions, we’ll do: watch me do it, do it with me, do it by yourself (problem sets)

13 of 22

Join the slack channel

https://join.slack.com/t/gcgenomeanalysis/shared_invite/zt-1h6ux1awi-dODwvMAfc6UkDbUEchpVzA

This is easiest for me to answer questions outside of class, and post links to slides.

14 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

15 of 22

Slide Deck

16 of 22

Suggested reading

  1. A diagnosis for all rare genetic diseases: the horizon and the next frontier. https://www.sciencedirect.com/science/article/pii/S0092867419302235 [1]
  2. Settling the score. https://www.nature.com/articles/nrg.2017.52?proof=t. [2]
  3. Whole-genome sequencing of patients with rare diseases in a national health system. https://www.nature.com/articles/s41586-020-2434-2 [3]
  4. Next-generation diagnostics and disease-gene discovery with the Exomiser. https://www.nature.com/articles/nprot.2015.124 [4]

1. Boycott KM, Hartley T, Biesecker LG, Gibbs RA, Micheil Innes A, Riess O, et al. A Diagnosis for All Rare Genetic Diseases: The Horizon and the Next Frontiers. Cell. 2019. pp. 32–37. doi:10.1016/j.cell.2019.02.040

2. Eilbeck K, Quinlan A, Yandell M. Settling the score: variant prioritization and Mendelian disease. Nat Rev Genet. 2017;18: 599–612.

3. Ouwehand WH, on behalf of the NIHR BioResource and the, 000 Genomes Project. Whole-genome sequencing of rare disease patients in a national healthcare system. doi:10.1101/507244

4. Smedley D, Jacobsen JOB, Jäger M, Köhler S, Holtgrewe M, Schubach M, et al.

17 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

18 of 22

Try logging in to the cluster

You need:

  1. BCCHR Account Username + Password (handy)
  2. VPN (not needed if on BCCHR wifi)
  3. Terminal application (Mac Terminal or MobaXTerm
  4. Then…��ssh <username>@gpcc-node01.bcricwh.lanssh prichmond@gpcc-node01.bcricwh.lan

ssh sophie.albert@gpcc-node01.bcricwh.lan

  • When you’re logged in, then come see me and get your patient description.

19 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

20 of 22

Case Assignments

Sophie - Case 1

Kelvin - Case 5

Mitch - Case 6

Tessa - Case 7

Yvette - Case 8

Sydney - Case 10

21 of 22

Today’s Outline (October 31st)

  • Who is Phil Richmond?
  • Course overview
  • Whole genome sequencing in the diagnosis of rare genetic disorders
  • Logging in to the cluster
  • Assigning patient cases
  • Install of necessary software

22 of 22

Software

Slides: https://docs.google.com/presentation/d/10Nm2C2FyGBADgm2T_iKzF3sIB-wYWD1QMvgjLRCGXZQ/edit#slide=id.g15e369fe30b_0_132

You should have:

  1. VPN
  2. Terminal capacity (native on Mac, or MobaXTerm)
  3. FileZilla
  4. IGV - https://software.broadinstitute.org/software/igv/
  5. File Server Mounting
    1. Mac: SSHFS - https://osxfuse.github.io
    2. PC: http://www.secfs.net/winfsp/