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$399 Personal Genome Service
$2,500 Health Compass service
$985 deCODEme(November 2007)
(November 2007)
(April 2008)
$350,000 Whole-genome sequencing(November 2007)
Genetic Information Nondiscrimination Act(May 2008)
Whole-genome sequencing
Comparative genomicsGenome resequencing
Structural variation analysis
Polymorphism discoveryMetagenomicsEnvironmental
sequencingGene expression profiling
Applications
GenotypingPopulation genetics
Migration studiesAncestry inference
Relationship inferenceGenetic screening
Drug targetingForensics
CS273a Lecture 9, Aut08, Batzoglou
Sequencing applications
Demand for more sequencing
Sequencing technology improvement
Increase in sequencing data output
New sequencing applications
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technologySanger sequencing
1975 1980 20081990 2000
$10.00
$1.00
$0.10
$0.01
Cost per finished bp:
Read length: 15 – 200 bp 500 – 1,000 bp
Throughput: “grad-student years” 2 ∙ 106 bp/day
Fred Sanger
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technologySanger sequencing
3 ∙ 109 bp
1x coverage
10x coverage
2 ∙ 106 bp/day= 40 years
× 3 ∙ 109 bp
10x coverage × 3 ∙ 109 bp × $0.001/bp = $30 million
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Pyrosequencing on a chip
Mostafa Ronaghi, Stanford Genome Technologies Center
454 Life Sciences
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technologyNext-generation sequencing
Read length: 250 bp
Throughput: 300 Mb/day
Cost: ~ 10,000 bp/$
De novo: yes
Genome Sequencer / FLX
“short reads”
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Single Molecule Array for Genotyping—Solexa
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Polony Sequencing
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technologyNext-generation sequencing
Read length: ~ 35 bp
Throughput: 300 – 500 Mb/day
Cost: ~ 100,000 bp/$
De novo: yes
Genome Analyzer SOLiD Analyzer
“microreads”
CS273a Lecture 9, Aut08, Batzoglou
Molecular Inversion Probes
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Illumina Genotype Arrays
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technology
Next-generation sequencing
Read length: 1 bp
Throughput: 1 – 2 Mb/day
Cost: 5,000 bp/$
De novo: no
Infinium Assay GeneChip Array
genotypes
“SNP chips”
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Nanopore Sequencing
http://www.mcb.harvard.edu/branton/index.htm
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technologyNext-generation sequencing
CS273a Lecture 9, Aut08, Batzoglou
Sequencing technologySequencing technology
Technology Read length (bp)
Throughput (Mb/day)
Cost (bp/$)
De novo
Sanger 1,000 2 1,000
454 250 300 10,000
Solexa / ABI 35 500 100,000
SNP chip 1 2 5,000
Application Sanger 454 Solexa/ABISNP chip
Bacterial sequencing $ sometimes
Mammalian sequencing $$$ ?not likely
today
Mammalian resequencing $$$ $ sort of
Metagenomics $ ?
Genotyping $$$ $$$ $$$
CS273a Lecture 9, Aut08, Batzoglou
Multiple Sequence Alignment
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Evolution at the DNA level
…ACGGTGCAGTTACCA…
…AC----CAGTCCACCA…
Mutation
SEQUENCE EDITS
REARRANGEMENTS
Deletion
InversionTranslocationDuplication
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Evolutionary Rates
OK
OK
OK
X
X
Still OK?
next generation
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
Orthology, Paralogy, Inparalogs, Outparalogs
CS273a Lecture 9, Aut08, BatzoglouCS273a Lecture 9, Fall 2008
