The document discusses the challenges and advancements in complete genome sequencing as a foundational element of P4 medicine, highlighting the need for large-scale sequencing to understand gene-disease associations. It emphasizes the importance of complementary systems approaches and offers insights into the sequencing process, quality metrics, and operational capacity of complete genomics. Overall, it concludes that advancements in sequencing technology and methods present significant opportunities for progress in genomic medicine.

1. Complete Genome Sequencing
Systems Biology as a Foundation of P4 Medicine
Clifford A. Reid, Ph.D.
Chief Executive Officer
© 2010 Complete Genomics, Inc.

2. Our Motivation
Why have clinically relevant associations between
genes and diseases been so difficult to find?
© 2010 Complete Genomics, Inc. 2

3. Our Motivation
Why have clinically relevant associations between
genes and diseases been so difficult to find?
1. Difficult to understand inner
workings and all dependencies in
regulatory pathways
2. Complete human genome
sequencing on a massive scale is
critical (but far from sufficient)
3. Need other systems approaches,
many focused studies, and
extensive computer modeling
© 2010 Complete Genomics, Inc. 3

4. High Quality Assembled Sequence at Low Cost
Estimated false positive rate 1 in 100,000 bases
© 2010 Complete Genomics, Inc. Drmanac et al. Science (2010) 327:78-81 4

5. Institute for Systems Biology: Family Genome
Sequence
2 Healthy parents + 2 Children Multiple Data Accuracy Analyses
with Miller syndrome
• Mendelian Inconsistencies
• Compare CGI genome sequence to
independent exome sequence
• Compare CGI genome sequence to
targeted resequencing and genotyping
• Consider as replicates ~25% of genome
where both children are identical twins
Four Genomes Sequenced Error rate estimates for Complete
by Complete Genomics; Genomics data (called bases):
Children independently • In Exome: 8.1 x 10-6
Exome sequenced • Genome-wide: 1.1 x 10-5
• Family False+: 3.3 x 10-6
Roach et al. Science 2010 328:636-9

6. Genomic landscape of somatic mutations in a lung tumor
Mutation Density
(1Mb Window)
Copy Number (Agilent)
Blue—Loss
Structural Variations Red—Gain
Blue—Intra chr
Red—Inter chr
LOH (SNP 6.0)
Genentech Bioinformatics Lee et al. 2010 Nature 465:473-477 6

7. Fewer mutations in coding and promoter regions
20.00 17.70
#mutations/Mbp
15.00 12.50*
10.50*
10.00
5.00
0.00
Genome- Protein coding Promoter -2kb
average
Genentech Bioinformatics Lee, et al. 2010 Nature 465:473-477 7

8. Fewer mutations in expressed genes
Expressed genes have fewer mutations
Depletion of expressed genes in the mutant group
(even lower in transcribed strand)
Not expressed Expressed
Genentech Bioinformatics Lee, et al. 2010 Nature 465:473-477

9. Large-Scale Complete Human Genome Analysis
Has Never Been Simpler
1. Researcher sends DNA
samples to Complete Genomics
2. Complete Genomics performs
library prep, sequencing, assembly
and analysis
3. Complete Genomics sends results--
variant files, annotations and summary
report--to researcher
© 2010 Complete Genomics, Inc. 9

10. Complete Genomics New Production Sequencer
1
© 2010 Complete Genomics, Inc. 10

11. Scaling Human Genome Sequencing Service
Samples  DNB Arrays DNB Arrays  Data Data  Genomes
Robotic Sample QC and Preparation 400 Whole Human Genomes/Month Data: 5,000 Cores + 2,000 Tb Disk
Service Advantage Capacity Expansion
 Low cost genome sequencing service  Establish satellite centers around the
 “Cloud Sequencing”/ “Democratization” world
 Reliable, use it when you need it  Address markets with sample export
restrictions
 High-throughput genome center
 FedEx samples, Internet data delivery
 Expand capacity per satellite center
© 2010 Complete Genomics, Inc. 11

12. Conclusions
1.
Complete genome sequencing at large scale is critical to dissect
entangled gene regulation networks and molecular basis of our
diseases (but needs other complementary data and analyses.
2.
Current sequencing technology can provide the required
quality and throughput at an affordable cost.
3.
These are exciting times to be
in genomic medicine.
© 2010 Complete Genomics, Inc. 12

13. Thank You
© 2010 Complete Genomics, Inc.