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Ion Proton I well Ion 300 series well 454 Titanium well

3 TCTTCTTCTGGCTGCCAGCACGCCGGTTGTAGTGGGATCTCTTCGCGATC |||||||||||||||||||||||||||||||||||||||||||||||||| TCTTCTTCTGGCTGCCAGCACGCCGGTTGTAGTGGGATCTCTTCGCGATC AAACGCCAGATCACCCCCGTTAACCACTTCAGAACCGTGGGTGATGACCT ||||||||||||||||||||||||||||||||||||||||||||||+||| AAACGCCAGATCACCCCCGTTAACCACTTCAGAACCGTGGGTGATG-CCT TTGAAATCGAATCAGGTTGGTATCGCACAGATGCGACGGCACCACATTCT |||||||||||+|||||||||||||||||||||||||||||||||||||| TTGAAATCGAA-CAGGTTGGTATCGCACAGATGCGACGGCACCACATTCT GCATCGCGCTGAACATCGTCTCGATACGCCCTGGATAACGTTTATCCCAG |||||||||||||||||||||||||||||||||||||||||||||||||| GCATCGCGCTGAACATCGTCTCGATACGCCCTGGATAACGTTTATCCCAG TCA ||| TCA Base Q20 Reads on Ion Proton™ I Chip

100 base200 base 300 base400 base

CGCTAAGTAATATTCGCCCCGTTCACACGATTCCTCTGTAGTTCAGTCGGTAGAACGGCGGACTGTTAATCCGTATGTCACTGGTTCGAGTCCAGTCAGA |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| CGCTAAGTAATATTCGCCCCGTTCACACGATTCCTCTGTAGTTCAGTCGGTAGAACGGCGGACTGTTAATCCGTATGTCACTGGTTCGAGTCCAGTCAGA GGAGCCAAATTCTAAAAATTCGCTTTTTTAGCGCAATGTCACTGACCTTAGTTGAACATTGTTTTTTAACGGATAGCGGGTTTTTAACATCTTAAGCGCC |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| GGAGCCAAATTCTAAAAATTCGCTTTTTTAGCGCAATGTCACTGACCTTAGTTGAACATTGTTTTTTAACGGATAGCGGGTTTTTAACATCTTAAGCGCC CTCGACCTTTATGGTTGAGGGCGTTTTGCTATGAACGCCATCACCATTTTCCCCTCGATTATAAAACTTGAGTTATTCAGTAGTCTCCCCTCTTGCAACT |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| CTCGACCTTTATGGTTGAGGGCGTTTTGCTATGAACGCCATCACCATTTTCCCCTCGATTATAAAACTTGAGTTATTCAGTAGTCTCCCCTCTTGCAACT CACACCCAAAACTGCCTAACGAAAAGTTATTAATTTTCAATCATATTGCTATCAGTATTTACATTTTTTCGCTGTGCTAGAAAGGGCGCATTTATGTTAG |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| CACACCCAAAACTGCCTAACGAAAAGTTATTAATTTTCAATCATATTGCTATCAGTATTTACATTTTTTCGCTGTGCTAGAAAGGGCGCATTTATGTTAG CTCGTTCAGGGAAGGTAAGCATGGCTACGAAGAAGAGAAGTGGAGAAGAAATAAATGACCGACAAATATTATGCGGGATGGGAATTAAACTACGCCGCTT |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| CTCGTTCAGGGAAGGTAAGCATGGCTACGAAGAAGAGAAGTGGAGAAGAAATAAATGACCGACAAATATTATGCGGGATGGGAATTAAACTACGCCGCTT AACTGCGGGTATCTGTCTGATAACT ||||||||||||||||||||||||| AACTGCGGGTATCTGTCTGATAACT

RED = “0” background trace (no signal as nucleotide flows in) BLUE = “1“ signal trace (positive signal on top of background) t=0 t=1.0 sec pH=8.0 pH= pH units Differential signal: 0.02 pH units for Single base extension, proportional For multiple bases 100 pH samples per second No incorporation (“0”) incorporation (“1”)

Confidential and Proprietary—DO NOT DUPLICATE 7

8

9 (a) (b)

10 Ion Proton™ OneTouch System Ion Proton™ SequencerProton™ Torrent Server Ion Kits

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The Torrent Suite SDK Guide is available at /DOC /DOC-1556 And additional information at it.hosted.jivesoftware.com/docs/DOC Torrent Suite Virtual machines are available for developer prototyping at – Penguin Computing: – Amazon AMI: search “ion-torrent” or use AMI-e94d9c80 at Amazon Web Services – Download to run locally – Grants of free time on Amazon Cloud for plug-in developers Torrent Suite Virtual Machine

AmpliSeq™ Assay Process

Ion AmpliSeq™ Comprehensive Cancer Panel 409 genes, ~16000 amplicons 4-pool design: > ~4,000 amplicons per pool DNA input: 40ng (10ng/ pool) FFPE compatible ~ 350x average depth of coverage using a 318 chip Literature and database review COSMIC mutation frequency >2% Genes cited in tumors of multiple types PharmGKB Pathways Signaling cascades Apoptosis DNA repair NF-kappaβ-related transcription regulators Inflammatory response and growth factor genes AmpliSeq™ Cancer Mutation Hotspot Panel (46 genes)

Ion AmpliSeq™ CCP Performance Uniformity: % of bases covered at >20% of the mean depth of coverage Coverage Uniformity Coverage Specificity Coverage Depth (318 chip) Specificity: % of bases that are Within the targeted regions Depth: average coverage across all target bases, for a 318 chip run

AmpliSeq Comprehensive Cancer Panel 17Confidential and Proprietary—DO NOT DUPLICATE Majority of bases are ≥ Q30 % Q % Most Common Read Length~130 bp Mean Raw Accuracy (1X)99.2%

Ion AmpliSeq™ Inherited Disease Panel 325 genes, ~10500 amplicons Coding exons of 325 genes 3-pool design: ~3,500 primers per pool 30ng DNA input (10ng per pool) Standard amplicon size (average 197 bases) 245 disorders 87 genes Neuromuscular 159 disorders 62 genes Heart disease 193 disorders 75 genes Developmental 46 disorders 28 genes Metabolic 210 disorders 73 genes Other (inherited cancer, blindness, etc)

Ion AmpliSeq™ IDP Performance Uniformity: % of bases covered at >20% of the mean depth of coverage Coverage Uniformity Coverage Specificity Coverage Depth (316 chip) Specificity: % of bases that are Within the targeted regions Depth: average coverage across all target bases, for a 316 chip run

AmpliSeq Inherited Disease Panel 20Confidential and Proprietary—DO NOT DUPLICATE Majority of bases are ≥ Q30 % Q % Most Common Read Length~180 bp Mean Raw Accuracy (1X)99.1%

Ampliseq™ Designer 1.2 May 2012 Number of Pools 2—4 (2 pools typical) Cumulative target sequence up to 1 Mb Primer pool size24 to 3072 amplicons in one tube User Interface Interface Enhancements Integration with UCSC browser Target Design Rate *> 85% Coverage Uniformity *> 85% On Target Bases *> 80% Assay design results < 2.5 hours for 10kb < 48 hours up to 250kb Oligo synthesis + Deliveries4 weeks

ioncommunity.lifetechnologies.com

23 Ion Community Rate of Growth *94% growth in last 6 months *135% growth in last 6 months *55% growth in last 6 months

Ion Torrent 318 (Paired End) PerformanceNew May 2012 Benchmark 200 b AQ20 unfiltered 5.832M AQ20 bases2.07Gb E. coli 100%442.5X US$1M for making 2-fold improvement

SFF Compression Challenge Two Weeks 10X Faster 60% Better Compression DAT Compression Challenge Two Weeks Same Speed 20% Better Compression Smith-Waterman (SW) Alignment Challenge: Results: 75 competitors Two week Competition, $5000 prize 5.5x speed improvement 36k SW per sec.  203k SW per sec. Basecaller Challenge Two Weeks 3.5x faster code Maintains call accuracy