DNA SEQUENCING: EMERGING TECHNOLOGIES AND APPLICATIONS

Transcription

1 DNA SEQUENCING: EMERGING TECHNOLOGIES AND APPLICATIONS BIO045E February 2014 John Bergin Project Analyst ISBN: BCC Research 49 Walnut Park, Building 2 Wellesley, MA USA (toll-free within the USA), or (+1) information@bccresearch.com

2 TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY GOALS AND OBJECTIVES 2 REASONS FOR DOING THE STUDY 2 INTENDED AUDIENCE 3 SCOPE AND FORMAT 3 METHODOLOGY 4 INFORMATION SOURCES 4 RELATED BCC RESEARCH REPORTS 5 ANALYST CREDENTIALS 5 BCC RESEARCH ONLINE SERVICES 5 DISCLAIMER 6 CHAPTER 2 EXECUTIVE SUMMARY 8 SUMMARY TABLE GLOBAL VALUE OF SEQUENCING PRODUCTS AND SERVICES, BY TYPE, SUMMARY FIGURE GLOBAL VALUE OF SEQUENCING PRODUCTS AND SERVICES, BY TYPE, ($ 9 9 CHAPTER 3 OVERVIEW 12 INTRODUCTION 12 TABLE 1 SCOPE OF THIS REPORT 12 SEQUENCING MARKET 13 TABLE 2 GLOBAL VALUE OF THE SEQUENCING MARKET BY DELIVERED FORMAT, TABLE 3 SEQUENCING KEY GROWTH DRIVING FORCES, THROUGH SEQUENCING PRODUCTS 16 SEQUENCING INSTRUMENTS AND CONSUMABLES 16 SAMPLE PREPARATION REAGENTS AND KITS 16 BIOINFORMATICS 17 SEQUENCING SERVICES 17 SEQUENCING PRODUCT LIFE CYCLE STATUS 17 TABLE 4 LIFE CYCLE OF DNA SEQUENCING TECHNOLOGIES 18 NEXT-GENERATION SEQUENCING INDUSTRY 18 TABLE 5 SUMMARY OF NEXT-GENERATION SEQUENCING INDUSTRY SECTORS CHAPTER 4 TECHNOLOGIES 21 IMPORTANCE OF DNA 21 TABLE 6 DNA CHEMICAL BUILDING BLOCKS 21 TABLE 7 DNA TRANSLATION AND TRANSCRIPTION 21 TABLE 8 LONG-RANGE DNA STRUCTURE 22 GENETIC VARIATION AND ANALYSIS 23 TABLE 9 GENETIC VARIANT TYPES 23 GENETIC ANALYSIS TECHNOLOGIES 24 TABLE 10 IMPORTANT MOLECULAR DIAGNOSTIC PLATFORMS BY COMPANY 24 SEQUENCING IN CLINICAL APPLICATIONS 25 TABLE 11 GENETIC TESTING EVOLUTION 25

3 TABLE 12 KEY NEAR- TO MID-TERM SEGMENTS FOR NEXT-GENERATION SEQUENCING DIAGNOSTICS SEQUENCING TECHNOLOGIES 27 HISTORY OF DNA SEQUENCING 27 TABLE 13 DNA SEQUENCING HISTORICAL TIMELINE, TABLE 14 SEQUENCING TECHNOLOGY DEVELOPMENT, TABLE 15 EFFECT OF NEW SEQUENCING TECHNOLOGIES ON COST AND TIME TO SEQUENCE A SINGLE HUMAN GENOME, 2001 AND 2013 ($) SANGER SEQUENCING TECHNOLOGY 34 TABLE 16 SANGER SEQUENCING SUMMARY 34 TABLE 17 SANGER SEQUENCING IMPROVEMENTS 35 NEXT-GENERATION SEQUENCING PLATFORMS 35 TABLE 18 NEXT-GENERATION SEQUENCING TECHNOLOGIES 35 TABLE 19 ROCHE NEXT-GENERATION SEQUENCING WORKFLOW 36 TABLE 20 ILLUMINA NEXT-GENERATION SEQUENCING WORKFLOW 37 TABLE 21 LIFE TECHNOLOGIES NEXT-GENERATION SEQUENCING WORKFLOW 38 BENCHTOP SEQUENCERS 38 TABLE 22 BENCHTOP SEQUENCER PLATFORMS 38 INFORMATICS TECHNOLOGIES 39 TABLE 23 NEXT-GENERATION SEQUENCING BIOINFORMATICS WORKFLOW 40 BASE CALLING 40 MAPPING TO A REFERENCE SEQUENCE 41 TABLE 24 SEQUENCE ANNOTATION STEPS 42 VARIANT ANALYSIS 42 CLINICAL SEQUENCING TECHNOLOGY CHALLENGES 43 TABLE 25 FUTURE CHALLENGES FOR IMPLEMENTING CLINICAL NEXT-GENERATION SEQUENCING TOP TEN CLINICAL NEXT-GENERATION SEQUENCING INITIATIVES 44 TABLE 26 TOP 10 CLINICAL NEXT-GENERATION SEQUENCING PROJECTS 44 1,000 GENOMES PROJECT 45 ARCHON X PRIZE IN GENOMICS 45 BASIC3 PROJECT 46 CANCER GENOME ATLAS 46 CANCER MOON SHOTS PROGRAM 47 CLARITY CHALLENGE 48 ENCODE PROJECT 48 GENOME IN A BOTTLE 48 MILLION VETERAN PROGRAM 49 NEUROMICS CONSORTIUM CHAPTER 5 DNA SEQUENCING APPLICATIONS 51 INTRODUCTION 51 FIGURE 1 NUMBER OF SEQUENCED GENOMES PER YEAR, (NO.) 51 GENETIC ANALYSIS 53 TABLE 27 COMPARISON OF GENETIC ANALYSIS FORMATS 54 TABLE 28 SEQUENCING ANALYSIS APPLICATIONS 55 TABLE 29 DE NOVO VERSUS RESEQUENCING REQUIREMENTS 56 DE NOVO WHOLE GENOME SEQUENCING 57

4 RESEQUENCING 57 WHOLE GENOME RESEQUENCING 58 TARGETED RESEQUENCING 59 SEQ-BASED METHODS 59 TABLE 30 GENETIC ANALYSIS APPLICATIONS WHERE SEQUENCING COMPETES WITH MICROARRAYS CHIP-SEQ 60 TABLE 31 COMPARISON OF SEQUENCING WITH MICROARRAYS FOR CHIP APPLICATIONS DNASE-SEQ 61 RNA-SEQ 61 TABLE 32 COMPARISON OF SEQUENCING AND MICROARRAYS FOR GENE EXPRESSION ANALYSIS METHYL-SEQ 63 STRUCTURAL VARIATION STUDIES 63 COMPLEMENTARY SEQUENCING AND MICROARRAY PLATFORMS 64 SEQUENCING END-USE APPLICATIONS 65 RESEARCH 65 CONSUMER SEQUENCING 67 TABLE 33 GENETIC ANALYSIS PLATFORM COMPARISON 67 AGRICULTURAL SEQUENCING 69 TABLE 34 SEQUENCING IMPACT ON AGRICULTURAL PRODUCT CLASSES 69 MICROBIAL SEQUENCING 70 TABLE 35 KEY APPLICATIONS IN MICROBIAL SEQUENCING 70 FORENSICS SEQUENCING 71 TABLE 36 KEY APPLICATIONS IN FORENSICS/ HUMAN IDENTITY SEQUENCING CHAPTER 6 CLINICAL NEXT-GENERATION SEQUENCING APPLICATIONS 74 INTRODUCTION 74 TABLE 37 CLINICAL NEXT-GENERATION SEQUENCING NEAR TO MID-TERM APPLICATIONS CANCER APPLICATIONS 75 TABLE 38 CANCER APPLICATIONS 75 MENDELIAN DISORDERS APPLICATIONS 77 TABLE 39 MENDELIAN DISORDERS APPLICATIONS 77 SCREENING APPLICATIONS 78 TABLE 40 SCREENING APPLICATIONS 78 TABLE 41 ETHICAL ISSUES ASSOCIATED WITH PRENATAL AND NEWBORN SCREENING INFECTIOUS DISEASE APPLICATIONS 81 TABLE 42 INFECTIOUS DISEASE APPLICATIONS 81 COMMON DISORDERS APPLICATIONS 83 TABLE 43 COMMON DISORDER APPLICATIONS CHAPTER 7 SEQUENCING INDUSTRY 87 INTRODUCTION 87 TABLE 44 SUMMARY OF KEY SEQUENCING INDUSTRY SEGMENTS 87 NEXT-GENERATION SEQUENCING INSTRUMENT INDUSTRY 88

5 TABLE 45 NEXT-GENERATION SEQUENCING INSTRUMENT COMPANIES: COMMERCIAL PHASE TABLE 46 NEXT-GENERATION SEQUENCING INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 TABLE 47 NEXT-GENERATION SEQUENCING HIGH-THROUGHPUT INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 TABLE 48 NEXT-GENERATION SEQUENCING BENCHTOP INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 NEXT-GENERATION SEQUENCING TARGET ENRICHMENT INDUSTRY 93 TABLE 49 NEXT-GENERATION SEQUENCING-BASED TARGET ENRICHMENT INDUSTRY THIRD GENERATION SEQUENCING INDUSTRY 95 TABLE 50 3GS INDUSTRY 95 DIRECT-TO-CONSUMER GENETIC TESTING INDUSTRY 97 TABLE 51 DIRECT TO CONSUMER GENETIC TESTING INDUSTRY 98 SINGLE CELL GENOMICS INDUSTRY 99 TABLE 52 SINGLE CELL WORKFLOW 100 TABLE 53 SINGLE CELL GENOMIC ANALYSIS INDUSTRY 100 NGS-BASED PROTEOMICS INDUSTRY 101 TABLE 54 NGS-BASED PROTEOMICS INDUSTRY 101 SEQUENCING INFORMATICS INDUSTRY 102 TABLE 55 NEXT-GENERATION SEQUENCING CLINICAL INFORMATICS COMPANY POSITIONING TABLE 56 COMPANY POSITIONING WITHIN THE NGS-BASED GENOME INTERPRETATION INDUSTRY SEQUENCING INFORMATION TECHNOLOGY INDUSTRY 106 TABLE 57 NGS CLOUD COMPUTING NETWORK INDUSTRY 106 CLINICAL LABORATORY INDUSTRY 107 TABLE 58 LEADING U.S. CLINICAL LABORATORY IMPROVEMENT AMENDMENTS LABORATORIES WITH NEXT-GENERATION SEQUENCING DIAGNOSTICS PRENATAL DIAGNOSTICS INDUSTRY 110 TABLE 59 NEXT-GENERATION SEQUENCING-BASED PRENATAL DIAGNOSTICS INDUSTRY TABLE 60 FETAL FRACTION REPORTING BY NGS COMPANIES 112 TABLE 61 NORTH AMERICAN TEST COSTS AND PRICES ($) 112 TABLE 62 NEXT-GENERATION SEQUENCING-BASED NON-INVASIVE PRENATAL DIAGNOSTIC MARKET SHARE BY TEST REVENUE, 2013 (%) TABLE 63 NON-INVASIVE PRENATAL DIAGNOSTICS POTENTIAL FUTURE COMPETITORS SEQUENCING INDUSTRY ACQUISITIONS AND STRATEGIC ALLIANCES 115 ACQUISITIONS 115 TABLE 64 SEQUENCING INDUSTRY ACQUISITIONS, STRATEGIC ALLIANCES 117 TABLE 65 SEQUENCING STRATEGIC ALLIANCES, CHAPTER 8 SEQUENCING MARKETS 131 GROWTH DRIVING FORCES 131 TABLE 66 SEQUENCING INDUSTRY KEY GROWTH DRIVING FORCES 131 SEQUENCING MARKET SUMMARY 133

6 TABLE 67 GLOBAL VALUE OF THE SEQUENCING MARKET BY DELIVERED FORMAT, SEQUENCING INSTRUMENTS AND CONSUMABLES MARKET 135 TABLE 68 GLOBAL VALUE OF THE SEQUENCING INSTRUMENTS AND CONSUMABLES MARKET BY PRODUCT TYPE, THROUGH 2016 ($ SEQUENCING INSTRUMENTS AND CONSUMABLES BY PLATFORM 135 TABLE 69 GLOBAL VALUE OF SEQUENCING INSTRUMENTS BY PLATFORM, TABLE 70 NHGRI ADVANCED DNA SEQUENCING GRANTS, SEPTEMBER TABLE 71 GLOBAL VALUE OF THE SEQUENCING CONSUMABLES MARKET BY PLATFORM, NGS INSTRUMENTS AND CONSUMABLES BY PLATFORM 139 TABLE 72 GLOBAL VALUE OF NGS INSTRUMENTS AND CONSUMABLES BY INSTRUMENT CLASS, SEQUENCING INSTRUMENTS AND CONSUMABLES BY CLASS 140 TABLE 73 GLOBAL VALUE OF SEQUENCING INSTRUMENTS AND CONSUMABLES BY INSTRUMENT CLASS, SEQUENCING INSTRUMENTS AND CONSUMABLES BY END USER 142 TABLE 74 GLOBAL VALUE OF SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 75 GLOBAL VALUE OF SANGER SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 76 GLOBAL VALUE OF NGS SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 77 GLOBAL VALUE OF 3GS INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, SEQUENCING SAMPLE PREP MARKETS 146 TABLE 78 GLOBAL VALUE OF THE SEQUENCING SAMPLE PREP MARKET BY APPLICATION, SEQUENCING INFORMATICS MARKET 147 TABLE 79 GLOBAL VALUE OF THE SEQUENCING INFORMATICS MARKET BY SOFTWARE FUNCTION, SEQUENCING SERVICES MARKETS 148 SEQUENCING SERVICES MARKET BY END-USER 148 TABLE 80 GLOBAL VALUE OF SEQUENCING SERVICES BY END-USER MARKET, Research 149 Consumer Sequencing 150 TABLE 81 GENETIC TESTS SOLD IN THE DIRECT-TO-CONSUMER MARKET, THROUGH 2013 SEQUENCING SERVICES MARKETS BY TYPE OF ANALYSIS 152 TABLE 82 GLOBAL VALUE OF SEQUENCING SERVICES BY ANALYSIS TYPE, SEQUENCING SERVICES MARKET BY GENOME TYPE 154 TABLE 83 GLOBAL VALUE OF SEQUENCING SERVICES BY GENOME TYPE, THROUGH 2018 ($ APPLIED SEQUENCING SERVICES MARKET 155 TABLE 84 GLOBAL VALUE OF THE APPLIED SEQUENCING SERVICES MARKET BY APPLICATION, CLINICAL SEQUENCING MARKET

7 TABLE 85 CLINICAL SEQUENCING MARKET BY INDICATION, THROUGH 2018 ($ TABLE 86 CLINICAL SEQUENCING MARKET BY PLATFORM, THROUGH 2018 ($ TABLE 87 CLINICAL SEQUENCING MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 88 CLINICAL SEQUENCING MARKET BY TEST PURPOSE, THROUGH 2018 ($ CLINICAL NGS MARKET 159 TABLE 89 CLINICAL NGS MARKET BY DISEASE, 159 TABLE 90 CLINICAL NGS MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 91 CLINICAL NGS MARKET BY TEST PURPOSE, 161 CLINICAL NGS CANCER MARKETS 162 TABLE 92 CLINICAL NGS CANCER MARKET BY MARKET SEGMENT, THROUGH 2018 ($ TABLE 93 CLINICAL NGS CANCER MARKET BY TEST PURPOSE, THROUGH 2018 ($ TABLE 94 CLINICAL NGS CANCER MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ CLINICAL NGS CARDIOVASCULAR MARKETS 165 TABLE 95 CLINICAL NGS CARDIOVASCULAR DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 96 CLINICAL NGS CARDIOVASCULAR DIAGNOSTIC MARKET BY TEST COMPLEXITY, CLINICAL NGS MENDELIAN DISORDERS MARKETS 168 TABLE 97 CLINICAL NGS MENDELIAN DISORDER DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 98 CLINICAL NGS MENDELIAN DISORDER MARKET BY TEST COMPLEXITY CLINICAL NGS METABOLIC AND IMMUNE DISORDERS MARKETS 171 TABLE 99 CLINICAL NGS METABOLIC AND IMMUNE DISORDER DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 100 CLINICAL NGS METABOLIC AND IMMUNE DISORDER DIAGNOSTIC MARKET BY TEST COMPLEXITY, CLINICAL NGS NEUROLOGY MARKETS 173 TABLE 101 CLINICAL NGS NEUROLOGY MARKET FOR ALZHEIMER S DISEASE BY TEST PURPOSE, TABLE 102 CLINICAL NGS NEUROLOGY MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 103 AUTISM SPECTRUM DISORDERS COMPETITIVE POSITIONING 175 CLINICAL NGS NEWBORN SCREENING MARKETS 175 TABLE 104 CLINICAL NGS NEWBORN SCREENING MARKET BY TEST PURPOSE, TABLE 105 CLINICAL NGS NEWBORN SCREENING MARKET BY TEST COMPLEXITY, CLINICAL NGS PRENATAL DIAGNOSTIC MARKETS 177 TABLE 106 CLINICAL NGS PRENATAL DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 107 NGS PRENATAL DIAGNOSTIC MARKET BY TEST COMPLEXITY, THROUGH 2018 ($

8 CLINICAL NGS FOOD-BORNE ILLNESS MARKETS 180 TABLE 108 CLINICAL NGS FOOD-BORNE ILLNESS DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 109 CLINICAL NGS FOOD-BORNE ILLNESS DIAGNOSTIC MARKET BY TEST COMPLEXITY, CLINICAL NGS HUMAN LEUKOCYTE ANTIGEN TYPING MARKETS 181 TABLE 110 CLINICAL NGS HUMAN LEUKOCYTE ANTIGEN TYPING MARKET BY TEST PURPOSE, TABLE 111 CLINICAL NGS HUMAN LEUKOCYTE ANTIGEN TYPING MARKET BY TEST COMPLEXITY, SEQUENCING MARKETS BY GEOGRAPHIC REGION 183 TABLE 112 GLOBAL VALUE OF THE DNA SEQUENCING MARKET BY REGION, SEQUENCING INSTRUMENTS AND CONSUMABLES BY REGION 184 TABLE 113 GLOBAL VALUE OF THE SEQUENCING INSTRUMENT AND CONSUMABLES MARKET BY REGION, TABLE 114 GLOBAL VALUE OF THE SEQUENCING SAMPLE PREPARATION MARKET BY REGION, SEQUENCING INFORMATICS MARKET BY REGION 187 TABLE 115 GLOBAL VALUE OF THE SEQUENCING BIOINFORMATICS MARKET BY REGION, SEQUENCING SERVICES MARKET BY REGION 187 TABLE 116 GLOBAL VALUE OF THE SEQUENCING SERVICES MARKET BY REGION, UNITED STATES SEQUENCING MARKET 188 TABLE 117 GLOBAL VALUE OF THE U.S. SEQUENCING MARKET BY PRODUCT TYPE, GERMANY SEQUENCING MARKET 189 TABLE 118 GLOBAL VALUE OF THE GERMANY SEQUENCING MARKET BY PRODUCT TYPE, UNITED KINGDOM SEQUENCING MARKET 190 TABLE 119 GLOBAL VALUE OF THE U.K. SEQUENCING MARKET BY PRODUCT TYPE, CHINA SEQUENCING MARKET 190 TABLE 120 GLOBAL VALUE OF THE CHINA SEQUENCING MARKET BY PRODUCT TYPE, JAPAN SEQUENCING MARKET 191 TABLE 121 GLOBAL VALUE OF THE JAPAN SEQUENCING MARKET BY PRODUCT TYPE, CLINICAL NGS GEOGRAPHICAL MARKETS 192 NORTH AMERICA 192 TABLE 122 NORTH AMERICAN NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, EUROPE 193 TABLE 123 EUROPEAN NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, CHINA 194 TABLE 124 CHINESE NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, JAPAN

9 TABLE 125 JAPANESE NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, REST OF WORLD 195 TABLE 126 REST OF WORLD NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, CHAPTER 9 CLINICAL NGS PATENTS 198 TABLE 127 CLINICAL NEXT-GENERATION SEQUENCING PATENTS*, CLINICAL NEXT-GENERATION SEQUENCING PATENTS BY INDICATION 198 TABLE 128 CLINICAL NEXT-GENERATION SEQUENCING PATENTS BY INDICATION, CLINICAL NEXT-GENERATION SEQUENCING PATENT ISSUES 199 SINGLE-GENE PATENTS 200 TABLE 129 COMPOSITION OF MATTER CLAIMS RELATING TO SINGLE-GENE PATENTS STATUS OF SEQUENOM'S '540 PATENT LITIGATION CHAPTER 10 COMPANY PROFILES ANDME INC. 204 TABLE 130 VOLUME OF DATA BY GENOMIC REGION 204 ADAPTIVE BIOTECHNOLOGIES INC. 205 AGILENT TECHNOLOGIES INC. 206 ALMAC GROUP LTD. 207 AMBRY GENETICS 208 APPISTRY INC. 209 ASSURERX HEALTH 209 ASTRID BIOSCIENCE GMBH 210 ASURAGEN INC. 210 AVIIR INC. 211 BASE4 INNOVATION LTD. 211 BECKMAN COULTER 211 BERRY GENOMICS CO. LTD. 213 BGI 214 BINA TECHNOLOGIES INC. 215 BLUEPRINT GENETICS 216 BOREAL GENOMICS 216 CAMBRIDGE EPIGENETIX LTD. 217 TABLE 131 COMPANIES IN THE EPIGENETIC SEQUENCING INDUSTRY 217 CARIS LIFE SCIENCES 218 CEGAT GMBH 218 CHRONIX BIOMEDICAL 219 CLC BIO 219 CODIFIED GENOMICS LLC 220 CORIELL LIFE SCIENCES INC. 220 CORRELAGEN DIAGNOSTICS INC 221 COUNSYL INC 221 COURTAGEN LIFE SCIENCES INC 222 CYNVENIO BIOSYSTEMS INC 222

10 CYPHER GENOMICS INC. 223 DIOGENIX INC. 223 TABLE 132 MULTIPLE SCLEROSIS DIAGNOSTIC WORKFLOW 224 DNA ELECTRONICS LTD. 224 DNA LINK 225 DNANEXUS INC. 225 EAGLE GENOMICS, LTD. 226 ELECTRONIC BIOSCIENCES 226 ENZYMATICS INC. 227 EUROFINS MWG OPERON 227 EXIQON A/S 228 EXOSOME DIAGNOSTICS INC. 229 EXPRESSION ANALYSIS INC. 229 FOUNDATION MEDICINE 230 FULL GENOMES CORPORATION 231 GATC BIOTECH AG 231 GE HEALTHCARE 232 GENAPSYS 233 GENDX BV 233 GENE BY GENE LTD. 234 GENEDX INC. 234 GENEPEEKS INC. 235 GENEWIZ INC. 236 GENIA TECHNOLOGIES INC. 236 TABLE 133 COMMERCIAL NGS PLATFORM COMPETITIVE POSITIONING 236 GENOLOGICS LIFE SCIENCES SOFTWARE 237 GENOMATIX SOFTWARE GMBH 238 GENOMEQUEST INC. 239 GENOMIC HEALTH INC. 240 GIGAGEN INC. 241 GNUBIO INC. 241 GOOD START GENETICS INC. 242 ILLUMINA INC. 243 INGENUITY SYSTEMS INC. 245 INNOVATIONS EXCHANGE PTE LTD 246 INVITAE, INC. 247 IREPERTOIRE 247 KAILOS GENETICS 248 KELLBENX INC. 248 KNOME INC. 249 LABORATORY CORPORATION OF AMERICA INC. 250 LABORATORY FOR MOLECULAR MEDICINE 250 LASERGEN INC. 251 LIFE TECHNOLOGIES INC. 251 MACROGEN INC. 254 MAVERIX BIOMICS INC. 255 MD ANDERSON CANCER CENTER 255

11 MEDGENOME LABS PVT. LTD. 256 MEDOMICS LLC. 256 MIINOME INC. 257 MULTIPLICOM NV 257 MYRIAD GENETICS INC. 258 NABSYS INC. 259 NATERA INC. 259 NEWGENE LTD. 260 NOBLEGEN BIOSCIENCES 261 N-OF-ONE INC. 261 NOVARTIS AG 262 NUMERATE INC. 262 NXT-DX 263 OMICIA INC. 263 OMIXON BIOCOMPUTING KFT 264 ONCODNA SA 264 ONCOSPIRE GENOMICS 265 OXFORD GENE TECHNOLOGY 265 OXFORD NANOPORE TECHNOLOGIES 266 PACIFIC BIOSCIENCES OF CALIFORNIA INC. 267 PARABASE GENOMICS 269 PASTEL BIOSCIENCE LTD 269 PATHOGENETIX 270 PATHOGENICA 270 PATHOQUEST SAS 271 PERKIN ELMER INC. 272 PERSONAL GENOME DIAGNOSTICS INC. 274 PERSONALIS INC. 274 PICOSEQ 275 POPULATION GENETICS TECHNOLOGIES LTD. 276 PORTABLE GENOMICS LLC 277 PREVENTIONGENETICS INC. 277 QIAGEN 278 QUANTUMDX 280 RAINDANCE TECHNOLOGIES INC. 281 REAL TIME GENOMICS INC. 282 REPROGENETICS 282 RESPONSE GENETICS INC. 283 ROCHE HOLDING AG 283 SCIGENOM LABS 284 SENGENICS INTERNATIONAL PTE LTD. 284 SEQUENOM INC. 284 SEQUENTA INC. 286 SEQUOIA GENETICS CO. LTD. 286 SEVEN BRIDGES GENOMICS INC. 287 SIEMENS AG 287 SILICON VALLEY BIOSYSTEMS 288

12 SINGLE CELL TECHNOLOGY, INC. 289 SISTEMAS GENOMICOS 289 SOFTGENETICS LLC 290 SPIRAL GENETICS INC. 290 STATION X INC. 291 STRAND LIFE SCIENCES 291 STRATOS GENOMICS INC. 291 SUNDANCE DIAGNOSTICS INC. 292 SYAPSE 292 SYGNIS AG 293 SYNAPDX 293 THERMO FISHER SCIENTIFIC INC. 294 TRANSGENOMIC INC. 294 TROVAGENE INC. 295 TUTE GENOMICS, INC. 295 TWO PORE GUYS INC. 296 WARP DRIVE BIO LLC 296 YIKON GENOMICS CO. LTD. 297 ZS GENETICS 297 ZYMO RESEARCH CORPORATION 298

13 LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL VALUE OF SEQUENCING PRODUCTS AND SERVICES, BY TYPE, TABLE 1 SCOPE OF THIS REPORT 12 TABLE 2 GLOBAL VALUE OF THE SEQUENCING MARKET BY DELIVERED FORMAT, TABLE 3 SEQUENCING KEY GROWTH DRIVING FORCES, THROUGH TABLE 4 LIFE CYCLE OF DNA SEQUENCING TECHNOLOGIES 18 TABLE 5 SUMMARY OF NEXT-GENERATION SEQUENCING INDUSTRY SECTORS 18 TABLE 6 DNA CHEMICAL BUILDING BLOCKS 21 TABLE 7 DNA TRANSLATION AND TRANSCRIPTION 21 TABLE 8 LONG-RANGE DNA STRUCTURE 22 TABLE 9 GENETIC VARIANT TYPES 23 TABLE 10 IMPORTANT MOLECULAR DIAGNOSTIC PLATFORMS BY COMPANY 24 TABLE 11 GENETIC TESTING EVOLUTION 25 TABLE 12 KEY NEAR- TO MID-TERM SEGMENTS FOR NEXT-GENERATION SEQUENCING DIAGNOSTICS TABLE 13 DNA SEQUENCING HISTORICAL TIMELINE, TABLE 14 SEQUENCING TECHNOLOGY DEVELOPMENT, TABLE 15 EFFECT OF NEW SEQUENCING TECHNOLOGIES ON COST AND TIME TO SEQUENCE A SINGLE HUMAN GENOME, 2001 AND 2013 ($) TABLE 16 SANGER SEQUENCING SUMMARY 34 TABLE 17 SANGER SEQUENCING IMPROVEMENTS 35 TABLE 18 NEXT-GENERATION SEQUENCING TECHNOLOGIES 35 TABLE 19 ROCHE NEXT-GENERATION SEQUENCING WORKFLOW 36 TABLE 20 ILLUMINA NEXT-GENERATION SEQUENCING WORKFLOW 37 TABLE 21 LIFE TECHNOLOGIES NEXT-GENERATION SEQUENCING WORKFLOW 38 TABLE 22 BENCHTOP SEQUENCER PLATFORMS 38 TABLE 23 NEXT-GENERATION SEQUENCING BIOINFORMATICS WORKFLOW 40 TABLE 24 SEQUENCE ANNOTATION STEPS 42 TABLE 25 FUTURE CHALLENGES FOR IMPLEMENTING CLINICAL NEXT-GENERATION SEQUENCING TABLE 26 TOP 10 CLINICAL NEXT-GENERATION SEQUENCING PROJECTS 44 TABLE 27 COMPARISON OF GENETIC ANALYSIS FORMATS 54 TABLE 28 SEQUENCING ANALYSIS APPLICATIONS 55 TABLE 29 DE NOVO VERSUS RESEQUENCING REQUIREMENTS 56 TABLE 30 GENETIC ANALYSIS APPLICATIONS WHERE SEQUENCING COMPETES WITH MICROARRAYS TABLE 31 COMPARISON OF SEQUENCING WITH MICROARRAYS FOR CHIP APPLICATIONS TABLE 32 COMPARISON OF SEQUENCING AND MICROARRAYS FOR GENE EXPRESSION ANALYSIS TABLE 33 GENETIC ANALYSIS PLATFORM COMPARISON 67 TABLE 34 SEQUENCING IMPACT ON AGRICULTURAL PRODUCT CLASSES 69 TABLE 35 KEY APPLICATIONS IN MICROBIAL SEQUENCING 70 TABLE 36 KEY APPLICATIONS IN FORENSICS/ HUMAN IDENTITY SEQUENCING 71 TABLE 37 CLINICAL NEXT-GENERATION SEQUENCING NEAR TO MID-TERM APPLICATIONS TABLE 38 CANCER APPLICATIONS

14 TABLE HEADING TABLE 39 MENDELIAN DISORDERS APPLICATIONS 77 TABLE 40 SCREENING APPLICATIONS 78 TABLE 41 ETHICAL ISSUES ASSOCIATED WITH PRENATAL AND NEWBORN SCREENING TABLE 42 INFECTIOUS DISEASE APPLICATIONS 81 TABLE 43 COMMON DISORDER APPLICATIONS 84 TABLE 44 SUMMARY OF KEY SEQUENCING INDUSTRY SEGMENTS 87 TABLE 45 NEXT-GENERATION SEQUENCING INSTRUMENT COMPANIES: COMMERCIAL PHASE TABLE 46 NEXT-GENERATION SEQUENCING INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 TABLE 47 NEXT-GENERATION SEQUENCING HIGH-THROUGHPUT INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 TABLE 48 NEXT-GENERATION SEQUENCING BENCHTOP INSTRUMENT COMPETITOR MARKET SHARE BY INSTALLED INSTRUMENT BASE, DECEMBER 2013 TABLE 49 NEXT-GENERATION SEQUENCING-BASED TARGET ENRICHMENT INDUSTRY 93 TABLE 50 3GS INDUSTRY 95 TABLE 51 DIRECT TO CONSUMER GENETIC TESTING INDUSTRY 98 TABLE 52 SINGLE CELL WORKFLOW 100 TABLE 53 SINGLE CELL GENOMIC ANALYSIS INDUSTRY 100 TABLE 54 NGS-BASED PROTEOMICS INDUSTRY 101 TABLE 55 NEXT-GENERATION SEQUENCING CLINICAL INFORMATICS COMPANY POSITIONING TABLE 56 COMPANY POSITIONING WITHIN THE NGS-BASED GENOME INTERPRETATION INDUSTRY TABLE 57 NGS CLOUD COMPUTING NETWORK INDUSTRY 106 TABLE 58 LEADING U.S. CLINICAL LABORATORY IMPROVEMENT AMENDMENTS LABORATORIES WITH NEXT-GENERATION SEQUENCING DIAGNOSTICS TABLE 59 NEXT-GENERATION SEQUENCING-BASED PRENATAL DIAGNOSTICS INDUSTRY TABLE 60 FETAL FRACTION REPORTING BY NGS COMPANIES 112 TABLE 61 NORTH AMERICAN TEST COSTS AND PRICES ($) 112 TABLE 62 NEXT-GENERATION SEQUENCING-BASED NON-INVASIVE PRENATAL DIAGNOSTIC MARKET SHARE BY TEST REVENUE, 2013 (%) TABLE 63 NON-INVASIVE PRENATAL DIAGNOSTICS POTENTIAL FUTURE COMPETITORS TABLE 64 SEQUENCING INDUSTRY ACQUISITIONS, TABLE 65 SEQUENCING STRATEGIC ALLIANCES, TABLE 66 SEQUENCING INDUSTRY KEY GROWTH DRIVING FORCES 131 TABLE 67 GLOBAL VALUE OF THE SEQUENCING MARKET BY DELIVERED FORMAT, TABLE 68 GLOBAL VALUE OF THE SEQUENCING INSTRUMENTS AND CONSUMABLES MARKET BY PRODUCT TYPE, THROUGH 2016 ($ TABLE 69 GLOBAL VALUE OF SEQUENCING INSTRUMENTS BY PLATFORM, THROUGH 2018 ($ TABLE 70 NHGRI ADVANCED DNA SEQUENCING GRANTS, SEPTEMBER TABLE 71 GLOBAL VALUE OF THE SEQUENCING CONSUMABLES MARKET BY PLATFORM, TABLE 72 GLOBAL VALUE OF NGS INSTRUMENTS AND CONSUMABLES BY INSTRUMENT CLASS,

15 TABLE HEADING TABLE 73 GLOBAL VALUE OF SEQUENCING INSTRUMENTS AND CONSUMABLES BY INSTRUMENT CLASS, TABLE 74 GLOBAL VALUE OF SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 75 GLOBAL VALUE OF SANGER SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 76 GLOBAL VALUE OF NGS SEQUENCING INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 77 GLOBAL VALUE OF 3GS INSTRUMENTS AND CONSUMABLES BY CUSTOMER TYPE, TABLE 78 GLOBAL VALUE OF THE SEQUENCING SAMPLE PREP MARKET BY APPLICATION, TABLE 79 GLOBAL VALUE OF THE SEQUENCING INFORMATICS MARKET BY SOFTWARE FUNCTION, TABLE 80 GLOBAL VALUE OF SEQUENCING SERVICES BY END-USER MARKET, TABLE 81 GENETIC TESTS SOLD IN THE DIRECT-TO-CONSUMER MARKET, THROUGH 2013 TABLE 82 GLOBAL VALUE OF SEQUENCING SERVICES BY ANALYSIS TYPE, THROUGH 2018 ($ TABLE 83 GLOBAL VALUE OF SEQUENCING SERVICES BY GENOME TYPE, THROUGH 2018 ($ TABLE 84 GLOBAL VALUE OF THE APPLIED SEQUENCING SERVICES MARKET BY APPLICATION, TABLE 85 CLINICAL SEQUENCING MARKET BY INDICATION, THROUGH 2018 ($ TABLE 86 CLINICAL SEQUENCING MARKET BY PLATFORM, THROUGH 2018 ($ TABLE 87 CLINICAL SEQUENCING MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 88 CLINICAL SEQUENCING MARKET BY TEST PURPOSE, THROUGH 2018 ($ TABLE 89 CLINICAL NGS MARKET BY DISEASE, 159 TABLE 90 CLINICAL NGS MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 91 CLINICAL NGS MARKET BY TEST PURPOSE, 161 TABLE 92 CLINICAL NGS CANCER MARKET BY MARKET SEGMENT, THROUGH 2018 ($ TABLE 93 CLINICAL NGS CANCER MARKET BY TEST PURPOSE, THROUGH 2018 ($ TABLE 94 CLINICAL NGS CANCER MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 95 CLINICAL NGS CARDIOVASCULAR DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 96 CLINICAL NGS CARDIOVASCULAR DIAGNOSTIC MARKET BY TEST COMPLEXITY, TABLE 97 CLINICAL NGS MENDELIAN DISORDER DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 98 CLINICAL NGS MENDELIAN DISORDER MARKET BY TEST COMPLEXITY TABLE 99 CLINICAL NGS METABOLIC AND IMMUNE DISORDER DIAGNOSTIC MARKET BY TEST PURPOSE,

16 TABLE HEADING TABLE 100 CLINICAL NGS METABOLIC AND IMMUNE DISORDER DIAGNOSTIC MARKET BY TEST COMPLEXITY, TABLE 101 CLINICAL NGS NEUROLOGY MARKET FOR ALZHEIMER S DISEASE BY TEST PURPOSE, TABLE 102 CLINICAL NGS NEUROLOGY MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 103 AUTISM SPECTRUM DISORDERS COMPETITIVE POSITIONING 175 TABLE 104 CLINICAL NGS NEWBORN SCREENING MARKET BY TEST PURPOSE, TABLE 105 CLINICAL NGS NEWBORN SCREENING MARKET BY TEST COMPLEXITY, TABLE 106 CLINICAL NGS PRENATAL DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 107 NGS PRENATAL DIAGNOSTIC MARKET BY TEST COMPLEXITY, THROUGH 2018 ($ TABLE 108 CLINICAL NGS FOOD-BORNE ILLNESS DIAGNOSTIC MARKET BY TEST PURPOSE, TABLE 109 CLINICAL NGS FOOD-BORNE ILLNESS DIAGNOSTIC MARKET BY TEST COMPLEXITY, TABLE 110 CLINICAL NGS HUMAN LEUKOCYTE ANTIGEN TYPING MARKET BY TEST PURPOSE, TABLE 111 CLINICAL NGS HUMAN LEUKOCYTE ANTIGEN TYPING MARKET BY TEST COMPLEXITY, TABLE 112 GLOBAL VALUE OF THE DNA SEQUENCING MARKET BY REGION, TABLE 113 GLOBAL VALUE OF THE SEQUENCING INSTRUMENT AND CONSUMABLES MARKET BY REGION, TABLE 114 GLOBAL VALUE OF THE SEQUENCING SAMPLE PREPARATION MARKET BY REGION, TABLE 115 GLOBAL VALUE OF THE SEQUENCING BIOINFORMATICS MARKET BY REGION, TABLE 116 GLOBAL VALUE OF THE SEQUENCING SERVICES MARKET BY REGION, TABLE 117 GLOBAL VALUE OF THE U.S. SEQUENCING MARKET BY PRODUCT TYPE, TABLE 118 GLOBAL VALUE OF THE GERMANY SEQUENCING MARKET BY PRODUCT TYPE, TABLE 119 GLOBAL VALUE OF THE U.K. SEQUENCING MARKET BY PRODUCT TYPE, TABLE 120 GLOBAL VALUE OF THE CHINA SEQUENCING MARKET BY PRODUCT TYPE, TABLE 121 GLOBAL VALUE OF THE JAPAN SEQUENCING MARKET BY PRODUCT TYPE, TABLE 122 NORTH AMERICAN NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, TABLE 123 EUROPEAN NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, TABLE 124 CHINESE NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, TABLE 125 JAPANESE NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION,

17 TABLE HEADING TABLE 126 REST OF WORLD NEXT-GENERATION SEQUENCING DIAGNOSTIC MARKET BY APPLICATION, TABLE 127 CLINICAL NEXT-GENERATION SEQUENCING PATENTS*, TABLE 128 CLINICAL NEXT-GENERATION SEQUENCING PATENTS BY INDICATION, TABLE 129 COMPOSITION OF MATTER CLAIMS RELATING TO SINGLE-GENE PATENTS 200 TABLE 130 VOLUME OF DATA BY GENOMIC REGION 204 TABLE 131 COMPANIES IN THE EPIGENETIC SEQUENCING INDUSTRY 217 TABLE 132 MULTIPLE SCLEROSIS DIAGNOSTIC WORKFLOW 224 TABLE 133 COMMERCIAL NGS PLATFORM COMPETITIVE POSITIONING

18 LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL VALUE OF SEQUENCING PRODUCTS AND SERVICES, BY TYPE, ($ FIGURE 1 NUMBER OF SEQUENCED GENOMES PER YEAR, (NO.) 51 9