Genomic medicine aims to identify genetic variations that cause disease and inform treatment. While whole genome sequencing is technically possible for $1000, analysis costs remain high. Current clinical applications include diagnosing rare childhood disorders and guiding cancer treatment. Continued cost reductions and expanding biological knowledge databases will drive further innovation, though challenges around data interpretation and reporting remain. Large reference populations and functional studies are still needed to realize genomics' full potential in healthcare.
2. Goal of Genomic Medicine
Identify genetic variation that causes or contributes to
disease (diagnostic), informs treatment options or patient
care (therapeutic/prognostic), or provides other useful
clinical information
14. Total Cost of Sequencing
• Whole Genome:
• Approximately $5000 - $10,000
• Technically $1000 Genome is “here” with Illumina 10X
15. Total Cost of Sequencing
• Whole Genome:
• Approximately $5000 - $10,000
• Technically $1000 Genome is “here” with Illumina 10X
• Analysis cost >> Sequencing Cost
16. Total Cost of Sequencing
• Whole Genome:
• Approximately $5000 - $10,000
• Technically $1000 Genome is “here” with Illumina 10X
• Analysis cost >> Sequencing Cost
• But, do we need the whole genome?
23. It Sounds simple but…
• For every stage there are multiple programs available and
published in the literature
24. It Sounds simple but…
• For every stage there are multiple programs available and
published in the literature
• For every program there are a wide-variety of parameter
values and options. Defaults often “good enough” but
not always
25. It Sounds simple but…
• For every stage there are multiple programs available and
published in the literature
• For every program there are a wide-variety of parameter
values and options. Defaults often “good enough” but
not always
• Best combinations of programs and options not well
understood
26. It Sounds simple but…
• For every stage there are multiple programs available and
published in the literature
• For every program there are a wide-variety of parameter
values and options. Defaults often “good enough” but
not always
• Best combinations of programs and options not well
understood
• Protocols changing rapidly as new technologies and
methods developed
30. Discovering Disease-Causing Genetic Variants
4 million genetic variants
2 million associated with
protein-coding genes
10,000 possibly
of disease
causing type
1500 <1%
frequency in
population
Clinically
Relevant Genetic
Variants
31. If a problem cannot be
solved, enlarge it.
--Dwight D. Eisenhower
Supreme Commander Allied Forces:
Second World War
34th President of the USA
4 million genetic variants
2 million associated with
protein-coding genes
10,000 possibly
of disease
causing type
1500 <1%
frequency in
population
37. Building Knowledge Take-Away
• Clinical utility relies on:
• Knowledge of background variation from well
sampled populations
• Knowledge of function of as much genomic
sequence as possible
• Well defined workflows
• Knowledge of sources of error
45. Potential Pitfalls with Annotation Sources
• Databases often overlap and agree, but there may be
disagreements
• Source of information: Predicted versus experimental
• Incorrect and out-of-date information
• Large-scale un-validated versus manually curated datasets
47. Genomic Medicine: In the Clinic
• Rapid diagnosis of genetic disease in NICU cases
• Quicker and cheaper than sequential genetic testing (traditional
method)
• 50 hour diagnosis
61. The Missing Pieces?
Exon 1 Intron 1 Exon 2Reference
Patient
Start
TAA
StopmRNA coding for protein
Exon 1 Intron 1 Exon 2
TAC
TyrSplice Site Loss
Missense/Frameshift Stop Gain
63. Where Are We Going?
Do whole genome anyway, use bioinformatics to filter
down to reportable/actionable information
4 million genetic variants
2 million associated with
protein-coding genes
10,000 possibly
of disease
causing type
1500 <1%
frequency in
population
Clinically
Relevant Genetic
Variants
68. Summary of Key Points
• Clinical application possible when cost and applicable
knowledge reach critical point
• Personalized genomic medicine is here already
• The genome alone isn’t enough
• Large population surveys of healthy individuals
• Sample from diverse human populations globally
• Large-scale surveys of genes, genetic elements, and their
functions
• Data, data, and more data required