Table of Contents
Part I
0. Executive Summary 21
1. Introduction 23
- Definitions and scope of the subject23
- Historical evolution of molecular diagnostics23
- Molecular biology relevant to molecular diagnostics24
- Genome24
- DNA24
- DNA polymerases25
- Restriction endonucleases25
- DNA methylation25
- RNA26
- RNA polymerases26
- MicroRNAs27
- DNA transcription27
- Chromosomes27
- Telomeres28
- Mitochondrial DNA28
- Genes29
- The genetic code29
- Gene expression29
- DNA sequences30
- Junk DNA30
- Single nucleotide polymorphisms30
- Genotype and haplotypes31
- Replication of the DNA helix31
- Proteins32
- Proteomics32
- Monoclonal antibodies32
- Aptamers32
- Basics of molecular diagnostics33
- Tracking DNA: the Southern blot33
- Pulsed-field gel electrophoresis34
- DNA Probes34
- The polymerase chain reaction34
- Basic Principles of PCR34
- Target selection35
- Detection of amplified DNA35
- Impact of human genome project on molecular diagnostics36
- Genetic variations in the human genome36
- Insertions and deletions in the human genome36
- Large scale variation in human genome37
- Variation in copy number in the human genome37
- Structural variations in the human genome38
- Mapping and sequencing of structural variation from human genomes39
- 1000 Genomes Project40
- Human Variome Project40
- Systems biology approach to molecular diagnostics41
- Biomarkers42
- Applications of molecular diagnostics42
2. Molecular Diagnostic Technologies 45
- Introduction45
- DNA extraction45
- Transrenal DNA45
- Sample preparation46
- Pressure Cycling Technology46
- Membrane immobilization of nucleic acids46
- Automation of sample preparation in molecular diagnostics47
- ABI PRISM 6700 Automated Nucleic Acid Workstation47
- BioRobot technology47
- COBAS AmpliPrep System47
- GENESIS FE500 Workcell47
- GeneMole48
- PCR BioCube48
- QIAsymphony48
- Tigris instrument system48
- Techniques for sample preparation that are suitable for automation49
- Xtra Amp Genomic DNA Extraction49
- Extraction of DNA from paraffin sections49
- Dynabead technology49
- Pressure Cycling Technology50
- SamPrep50
- Use of magnetic particles for automation in genome analysis50
- Companies involved in nucleic acid isolation51
- Novel PCR methods52
- Addressing limitations of PCR52
- Real-time PCR systems52
- Dyes used in real-time PCR53
- Commercially available real-time PCR systems54
- LightCycler PCR system54
- LightUp probes based on real-time PCR55
- Applications of real-time PCR55
- Limitations of real-time PCR56
- Improving the reliability of low level DNA analysis by real-time PCR56
- Guidelines for real-time quantitative PCR56
- Future applications of real-time Q-PCR57
- Reverse transcriptase (RT)-PCR57
- Standardized reverse transcriptase PCR58
- Single cell PCR58
- LATE-PCR58
- Cold-PCR59
- AmpliGrid-System59
- Digital PCR59
- Long and accurate PCR60
- Combined PCR-ELISA60
- Monitoring of gene amplification in molecular diagnostics61
- Non-PCR nucleic acid amplification methods61
- Linked Linear Amplification61
- Multiplex Ligation-Dependent Probe Amplification61
- Transcription mediated amplification62
- Rapid analysis of gene expression62
- WAVE nucleic acid fragment analysis system62
- DNA probes with conjugated minor groove binder63
- Rolling circle amplification technology63
- Gene-based diagnostics through RCAT65
- RCAT-immunodiagnostics65
- RCAT-biochips65
- RCAT-pharmacogenomics66
- Circle-to-circle amplification66
- Ramification amplification method66
- Single Primer Isothermal Amplification66
- Isothermal reaction for amplification of oligonucleotides67
- ICAN (Isothermal and Chimeric primer-initiated Amplification of Nucleic
Acids)67
- Technologies for signal amplification68
- 3 DNA dendrimer signal amplification68
- Hybridization signal amplification method69
- Signal mediated amplification of RNA technology70
- Invader assays70
- Hybrid Capture technology71
- Branched DNA test72
- Tyramide signal amplification73
- Non-enzymatic signal amplification technologies73
- Direct molecular analysis without amplification74
- Direct detection of dsDNA75
- Multiplex assays75
- Fluorescent in situ hybridization75
- Modifications of FISH77
- Direct visual in situ hybridization77
- Direct labeled Satellite FISH probes78
- Comparative genomic hybridization78
- Primed in situ labeling78
- Interphase FISH79
- FISH with telomere-specific probes79
- Multicolor FISH79
- Automation of FISH80
- Companies involved in FISH diagnostics80
- RNA diagnostics81
- Branched-chain DNA assay for measurement of RNA82
- Cycling probe technology83
- Invader RNA assays83
- Linear RNA amplification83
- Non-isotopic RNase cleavage assay84
- Nucleic acid sequence-based amplification84
- Q Beta replicase system86
- Solid Phase Transcription Chain Reaction86
- Transcriptome analysis86
- Visualization of mRNA expression in vivo87
- MicroRNA diagnostics87
- Real-time PCR for expression profiling of miRNAs87
- Microarray vs quantitative PCR foro measuring miRNAs88
- Use of LNA to explore miRNA88
- Nuclease Protection Assay to measure miRNA expression89
- Microarrays for analysis of miRNA gene expression89
- Modification of in situ hybridization for detection of miRNAs90
- Whole genome amplification90
- Companies that provide technologies for whole genome amplification90
- QIAGEN' s Repli-G system91
- GenomePlex™ Whole Genome Amplification91
- DNA sequencing92
- Companies involved in sequencing93
- Applications of next generation sequencing in molecular diagnostics94
- Genome-wide approach for chromatin mapping94
- Mitochondrial sequencing94
- Identification of unknown DNA sequences95
- Optical mapping95
- Gene expression analysis96
- Gene expression profiling on whole blood samples96
- Gene expression patterns of white blood cells97
- Gene expression profiling based on alternative RNA splicing97
- MAUI (MicroArray User Interface) hybridization98
- Monitoring in vivo gene expression by molecular imaging98
- Serial analysis of gene expression (SAGE)98
- Single-cell gene expression analysis98
- T cell receptor expression analysis99
- Tangerine"! expression profiling99
- Whole genome expression array100
- Ziplex"! system100
- Companies involved in gene expression analysis101
- Peptide nucleic acid technology102
- Use of PNA with fluorescence in situ hybridization102
- PNA and PCR103
- Use of PNA with biosensors103
- PNA-based PD-loop technology104
- PNA-DNA hybrid quadruplexes104
- Companies Involved in PNA Diagnostics104
- Locked nucleic acids105
- Electrochemical detection of DNA105
- Mediated nucleic acid oxidation106
- Detection of hybridized nucleic acid with cyclic voltametry106
- Electrochemical detection based on Toshiba' s CMOS technology107
- Concluding remarks on electrochemical DNA detection107
- Scorpions"! technology107
- The Scorpions reaction107
- Applications of Scorpion108
3. Biochips, Biosensors, and Molecular Labels 109
- Introduction to biochip technology109
- Applications of biochips in diagnostics109
- GeneChip110
- GeneChip Human Genome Arrays111
- AmpliChip CYP450111
- Electronic detection of nucleic acids on microarrays111
- Microchip capillary electrophoresis112
- Strand displacement amplification on a biochip112
- Rolling circle amplification on DNA microarrays112
- Fast PCR biochip112
- Multiplex microarray-enhanced PCR for DNA analysis113
- Multiplexed Molecular Profiling113
- Universal DNA microarray combining PCR and ligase detection reaction114
- Genomewide association scans114
- Whole genome chips/microarrays114
- Transposon insertion site profiling chip115
- Standardizing the microarrays115
- Companies involved in developing biochip technology for diagnostics116
- Future of biochip technology for molecular diagnostics117
- Microfluidic chips117
- Fish-on-chip118
- Lab-on-a-chip118
- LabCD118
- Micronics' microfluidic technology119
- Microfluidic automated DNA analysis using PCR119
- Microfluidic chips integrated with PET119
- Companies developing microfluidic technologies120
- Biosensor technologies120
- Classification of biosensor technologies121
- DNA-based biosensors122
- DNA hybridization biosensor chips122
- PCR-free DNA biosensor122
- DNA based biosensor to detects metallic ions123
- Genetically engineered B lymphocytes123
- Biosensors immunoassays123
- PNA (peptide nucleic acid)-based biosensors124
- Protein-based biosensors124
- Antibody biosensors124
- Cell-based biosensors (cytosensors)124
- Multicell biosensors125
- Microbial biosensors125
- Optical biosensors126
- Surface plasmon resonance technology126
- Label-free optical biosensor127
- Microsensors using with nano/microelectronic communications technology127
- Electrochemical sensors127
- Enzyme electrodes for biosensing127
- Conductometric sensors128
- Electrochemical genosensors128
- Electrochemical nanobiosensor128
- Bioelectronic sensors129
- Phototransistor biochip biosensor129
- Ribozyme-based sensors129
- RiboReporters130
- Concluding remarks and future prospects of biosensor technology130
- Companies developing biosensors for molecular diagnostics131
- Molecular labels and detection132
- Detection technologies for molecular labels133
- Fluorescence and chemiluminescence133
- Fluorescence technologies for label detection134
- Companies with fluorescence and chemiluminescence products134
- Molecular beacons135
- The Green fluorescent protein136
- Multiophoton detection radioimmunoassay137
- Multi-pixel photon counter137
- Enzyme labels and detection by fluorescence137
- Phase-sensitive flow cytometry138
- Microtransponder-based DNA diagnostics138
- Laboratory Multiple Analyte Profile139
- Multiple labels139
- Protein-DNA chimeras for detection of small numbers of molecules140
- Single molecule detection140
- Atomic force microscopy141
- Capillary electrophoresis141
- Confocal laser scanning141
- Spectrally resolved fluorescence lifetime imaging microscopy141
- Molecular imaging142
- Basic research in molecular imaging142
- Devices for molecular imaging143
- Molecular imaging in clinical practice143
- Challenges and future prospects of molecular imaging143
- Companies involved in molecular imaging143
- Nanobiotechnology for molecular diagnostics144
- Magnetic nanoparticles145
- Gold nanoparticles146
- Quantum dot technology146
- Nanotechnology on a chip147
- Nanogen' s NanoChip148
- Fullerene photodetectors for chemiluminescence detection on microfluidic
chip148
- Diagnostics based on nanopore technology148
- Nanosensors148
- Quartz nanobalance biosensor149
- PEBBLE nanosensors149
- Nanosensors for glucose monitoring149
- Cantilever arrays150
- Resonance Light Scattering technology150
- DNA nanomachines for molecular diagnostics151
- Nanobarcodes technology for molecular diagnostics151
- Qdot nanobarcode for multiplexed gene expression profiling152
- Role of nanobiotechnology in improving molecular diagnostics152
- Companies involved in nanomolecular diagnostics152
- Concluding remarks about nanodiagnostics155
- Future prospects of nanodiagnostics155
4. Proteomic Technologies for Molecular Diagnostics 157
- Introduction157
- Proteomic technologies157
- Biomarkers of disease157
- Proteomic tools for biomarkers157
- Search for biomarkers in body fluids158
- Captamers with proximity extension assay for proteins158
- Cyclical amplification of proteins158
- Detection of misfolded proteins by ELISA with exponential signal
amplification159
- Diagnostics based on designed repeat proteins159
- Differential Peptide Display159
- Light-switching excimer probes160
- MALDI-TOF Mass Spectrometry160
- Molecular beacon aptamer161
- Molecular beacon assay161
- Proteomic patterns161
- Real-time PCR for protein quantification163
- Protein biochip technologies163
- ProteinChip164
- LabChip for protein analysis165
- TRINECTIN proteome chip165
- Protein chips for antigen-antibody interactions molecular diagnostics165
- Microfluidic devices for proteomics-based diagnostics166
- Nanotechnology-based protein biochips/microarrays166
- Nanoparticle protein chip166
- Protein nanobiochip166
- Protein biochips based on fluorescence planar wave guide technology167
- New developments in protein chips/microarrays167
- Antibody microarrays168
- Aptamer-based protein biochip168
- Multiplexed Protein Profiling on Microarrays168
- Proteomic pattern analysis169
- Single molecule array169
- Viral protein chip169
- Commercial development of protein chips for molecular diagnostics170
- Proteome Identification Kit171
- Laser capture microdissection (LCM)171
- LCM technology171
- Applications of LCM in molecular diagnostics172
- Proteomic diagnosis of CNS disorders172
- Cerebrospinal fluids tests based on proteomics172
- Urine tests for CNS disorders based on proteins in urine173
- Diagnosis of CNS disorders by examination of proteins in the blood173
- Diagnosis of CNS disorders by examination of proteins in tears174
- Role of proteomics in the diagnosis of Alzheimer' s disease175
- Role of proteomics in the diagnosis of Creutzfeldt-Jakob disease175
- Future prospects of use of proteomics for diagnosis of CNS disorders175
- Concluding remarks on the use of proteomics in diagnostics175
5. Molecular Diagnosis of Genetic Disorders 177
- Introduction177
- Cytogenetics178
- FISH with probes to the telomeres178
- Single copy FISH probes178
- Comparative genomic hybridization179
- Use of biochips in genetic disorders179
- Representational oligonucleotide microarray analysis180
- SignatureChipR-based diagnostics for cytogenetic abnormalities180
- Diagnosis of genomic rearrangements by multiplex PCR180
- Quantitative fluorescent PCR180
- Mutation detection technologies181
- PCR-based methods for mutation detection182
- Cleavase Fragment Length Polymorphism182
- Direct dideoxy DNA sequencing182
- Digital Genetic Analysis (DGA)182
- Fluorescence-based directed termination PCR183
- Heteroduplex analysis183
- Restriction fragment length polymorphism184
- Single-stranded conformation polymorphism (SSCP) analysis184
- TaqMan real-time PCR184
- Non-PCR methods for mutation detection185
- Arrayed primer extension185
- BEAMing (beads, emulsion, amplification, and magnetics)185
- ELISA-protein truncation test186
- Enzymatic mutation detection186
- Specific anchor nucleotide incorporation186
- Conversion analysis for mutation detection187
- Biochip technologies for mutation detection187
- Combination of FISH and gene chips187
- Haplotype Specific Extraction188
- Technologies for SNP analysis188
- DNA sequencing189
- Electrochemical DNA probes189
- Use of NanoChip for detection of SNPs190
- Single base extension-tag array190
- Laboratory Multiple Analyte Profile190
- SNP genotyping with gold nanoparticle probes191
- PCR-CTPP (confronting two-pair primers)191
- Peptide nucleic acid probes for SNP detection191
- SNP genotyping on a genome-wide amplified DOP-PCR template192
- Pyrosequencing192
- Reversed enzyme activity DNA interrogation test192
- Smart amplification process version 2193
- Zinc finger proteins193
- UCAN method (Takara Biomedical)194
- Biochip and microarray-based detection of SNPs194
- SNP genotyping by MassARRAY194
- Electronic dot blot assay194
- Biochip combining BeadArray and ZipCode technologies195
- SNP-IT primer-extension technology195
- OmniScan SNP genotyping196
- Affymetrix SNP genotyping array196
- Concluding remarks on SNP genotyping196
- Limitations of SNP in genetic testing196
- Haplotyping versus SNP genotyping197
- Determination of copy number variations197
- Companies involved in developing technologies/products for SNP analysis198
- Prenatal DNA diagnosis200
- Amniocentesis200
- Chorionic villus sampling200
- Separating fetal cells in maternal blood for genetic diagnosis200
- Antenatal screening for Down' s syndrome201
- Fetal DNA in maternal blood201
- Molecular methods for prenatal diagnosis202
- aCGH for prenatal diagnosis202
- BAC HD Scan test202
- FISH for prenatal diagnosis203
- PCR for prenatal diagnosis203
- Plasma DNA sequencing to detect fetal chromosomal aneuploidies203
- In vivo gene expression analysis of the living human fetus204
- Noninvasive prenatal diagnosis of monogenic diseases204
- Digital relative mutation dosage204
- Massively parallel plasma DNA sequencing204
- Applications of prenatal diagnosis205
- Diagnosis of congenital infections206
- Diagnosis of eclampsia206
- Use of transrenal DNA for prenatal testing206
- Preimplantation genetic diagnosis207
- Technologies for preimplantation genetic diagnosis (PGD)207
- PCR for preimplantation genetic diagnosis207
- FISH for preimplantation genetic diagnosis207
- Microarrays for preimplantation genetic diagnosis208
- Conditions detected by preimplantation genetic diagnosis208
- The future of preimplantation genetic diagnosis209
- Companies involved in prenatal/preimplantation diagnosis210
- Cystic fibrosis210
- Detection of CFTR gene mutations211
- CFTR technologies of various companies211
- Genzyme' s CF gene sequencing212
- CF Plus™ Tag-It Cystic Fibrosis Kit212
- Asuragen' s bead array test213
- The Ambry CF Test213
- Biochip for CF diagnosis213
- Identification of CF variants by PCR/Oligonucleotide Ligation Assay214
- MassARRAYR system for high-throughput CFTR testing214
- Serum proteomic signature for CF using antibody microarrays214
- Guidelines for genetic screening for CF214
- Congenital adrenal hyperplasia215
- Primary immunodeficiencies215
- Hematological disorders216
- Hemoglobinopathies216
- Sickle cell anemia216
- Thalassemia217
- Paroxysmal nocturnal hemoglobinuria217
- Hemophilia218
- Hereditary hemochromatosis218
- Polycystic kidney disease218
- Hereditary metabolic disorders219
- Lesch-Nyhan Syndrome219
- Gaucher' s Disease219
- Acute Intermittent Porphyria220
- Phenylketonuria220
- Hereditary periodic fever220
- Achondroplasia220
- Molecular diagnosis of cardiovascular disorders221
- Coronary Heart Disease222
- Cardiomyopathy222
- Familial Hypertrophic Cardiomyopathy223
- Idiopathic dilated cardiomyopathy223
- Cardiac Arrhythmias223
- Long Q-T Syndrome223
- Familial atrial fibrillation224
- Idiopathic ventricular fibrillation224
- Congestive heart failure224
- Hypertension224
- Disturbances of blood lipids225
- Familial dyslipoproteinemias225
- Hypercholesterolemia225
- Thrombotic disorders226
- Factor V Leiden mutation226
- Pulmonary embolism226
- Molecular diagnosis of eye diseases227
- Molecular diagnosis of retinitis pigmentosa227
- Genetic screening for glaucoma227
- Role of molecular diagnostics in rheumatoid arthritis228
- Molecular diagnosis of neurogenetic disorders228
- Alzheimer' s disease230
- Down syndrome230
- Parkinson' s disease231
- Spinal muscular atrophy232
- Duchenne and Becker muscular dystrophy232
- Triple repeat disorders233
- Huntington disease233
- Fragile X syndrome234
- Charcot-Marie Tooth disease234
- Hereditary neuropathy with liability to pressure palsies235
- eNOS gene polymorphisms as predictor of cerebral aneurysm rupture235
- Mitochondrial disorders affecting the nervous system235
- Genetic testing for disease predisposition236
- Direct-to-consumer genetic tests236
6. Molecular Diagnosis of Infections 238
- Introduction238
- Molecular techniques for the diagnosis of infections238
- Antibody-enhanced microplate hybridization assays239
- Biosensors for detection of microorganisms239
- Ibis T5000"! Biosensor System239
- DNA enzyme immunoassay240
- DNA biochip/microarray in diagnosis of infections240
- DNA-based typing methods241
- Restriction fragment length polymorphism analysis241
- Ribotyping241
- Random amplified polymorphic DNA241
- Combinatorial DNA melting assay241
- Electrochemical detection of pathogens242
- Ligase chain reaction242
- Mass spectrometry for microbial identification242
- Metagenomic pyrosequencing242
- Multiplex PCR for detection of infections244
- LightCyclerR SeptiFast Test244
- VYOOR Sepsis Test244
- Dual priming oligonucleotide for multiplex PCR245
- NASBA for detection of microorganisms245
- Nucleic acid probes245
- Neutrophil CD11b expression as a diagnostic marker246
- Optical Mapping246
- PNA-FISH for diagnosis of infections246
- Quantitative reverse-transcription PCR for bacterial diagnostics247
- Rupture event scanning247
- Real-time single-molecule imaging of virus particles247
- Single-strand conformational polymorphism247
- SmartGene platform for identifying pathogens based on genetic sequences248
- Tessera array technology248
- Applications, advantages and limitations of molecular diagnostics248
- Molecular diagnostics versus other microbial detection technologies248
- Advantages of nucleic acid-based diagnostics in infections249
- Drawbacks of nucleic acid-based diagnostics in infections249
- Nanotechnology for detection of infectious agents250
- Bacterial and fungal infections250
- Mycobacterium tuberculosis252
- Conventional diagnosis of tuberculosis252
- Microscopic Observation Drug Susceptible Assay for tuberculosis252
- Molecular diagnostics for tuberculosis253
- Combined tuberculin testing and ELISpotPLUS assay254
- Biomarkers for tuberculosis255
- Diagnosis of drug-resistant M. tuberculosis infection255
- Cost-effectiveness of PCR in tuberculosis screening256
- Other mycobacteria256
- Chlamydial infections256
- Neisseria gonorrhoeae258
- Bacteria associated with bacterial vaginosis258
- Streptococcal infections258
- Group B Streptococci258
- Streptococcus pyogenes and Streptococcus dysgalactiae259
- Pseudomonas aeruginosa259
- Helicobacter pylori260
- Lyme disease260
- Mycoplasmas261
- Fungal infections261
- Viral infections262
- HIV/AIDS263
- Diagnosis of HIV263
- Neonatal screening of infants of HIV-positive mothers264
- Screening of cadaveric tissue donors264
- Detection of HIV provirus264
- Resolution of indeterminate Western blot264
- Global Surveillance of HIV-1 genetic variations265
- Genotyping for drug-resistance in HIV265
- Phenotyping as predictor of drug susceptibility/resistance in HIV266
- Tests used for quantification of HIV267
- Conclusions about HIV genotyping267
- Hepatitis viruses268
- Hepatitis A virus268
- Hepatitis B virus269
- Hepatitis C virus269
- Detection and quantification of HCV RNA270
- Quantification of HCV RNA levels as a guide to antiviral therapy271
- Electrochemical DNA chip for diagnosis of HCV271
- HCV Genotyping as a guide to therapy271
- Enteroviruses272
- Adenoviruses273
- Rhinoviruses273
- Herpes viruses273
- Herpes simplex virus273
- Genital and neonatal herpes simplex274
- Human cytomegalovirus infections274
- Epstein-Barr virus274
- Human papilloma virus275
- Molecular diagnostics for HPV275
- Detection of encephalitis viruses276
- West Nile and St. Louis encephalitis276
- Venezuelan equine encephalitis virus276
- Protozoal infections277
- Amebiasis277
- Cryptosporidium parvum277
- Malaria277
- Neurocysticercosis278
- Pneumocystis carinii278
- Toxoplasmosis278
- Infections of various systems279
- CNS infections279
- Molecular diagnosis in bacterial meningitis279
- Molecular diagnosis in herpes simplex encephalitis279
- Diagnosis of transmissible spongiform encephalopathies280
- Molecular diagnosis of respiratory viruses281
- SARS-associated coronavirus281
- Influenza viruses282
- Avian influenza284
- H1N1 influenza287
- Gastrointestinal infections289
- Periodontal infections290
- Diagnosis of urinary infections by a biosensor291
- Role of molecular diagnostics in septicemia291
- Limitations and needs of diagnostics for infections292
- Differentiation between live and antibiotic-killed bacteria292
- Cell-based methods for identifying pathogenic microorganisms293
- Cell-based virus assays293
- Cell-based detection of host response to infection293
- Role of molecular diagnostics in hospital acquired infections293
- Detection of hospital-acquired bacterial infections294
- Detection of methicillin-resistant S. aureus294
- Detection of vancomycin-resistant enterococci295
- Detection of hospital-acquired C. difficile295
- Bacterial genome sequencing in antimicrobial resistance295
- Detection of hospital-acquired viral infections296
- Molecular diagnosis of BK virus296
- Diagnosis of hospital-acquired rotavirus gastroenteritis296
- Molecular diagnostics and the microbiome297
- Human Microbiome Project297
- Application of metagenomics to study of the microbiome297
- MicroBiome Analysis Center298
- Concluding remarks and future prospects of diagnosis of infections298
- Rapid point-of-care diagnosis of infection299
- Diagnosis of viruses using protein fingerprinting301
- QIAplex PCR multiplex technology301
- Companies involved in molecular diagnosis of infectious diseases301
7. Molecular Diagnosis of Cancer 304
- Introduction304
- Cancer Genetics304
- Oncogenes304
- Tumor Suppressor Genes305
- p53306
- p16306
- Viruses and cancer307
- Detecting viral agents in cancer307
- Conventional cancer diagnosis308
- Molecular techniques for cancer diagnosis309
- Genome analysis at the molecular level310
- Mutation detection at molecular level311
- Expression profiling of tumor cells sorted by flow cytometry311
- MicroRNA expression profiling to classify human cancers311
- Biomarkers in cancer312
- Circulating nucleosomes in serum of cancer patients312
- Detection of DNA methylation313
- eTag assay system for cancer biomarkers315
- HAAH as a biomarker for cancer315
- LigAmp for detection of gene mutations in cancer315
- Mitochondrial DNA as a cancer biomarker316
- Oncoproteins as biomarkers for cancer316
- Sequencing-based approaches for detection of cancer biomarkers317
- Molecular fingerprinting of cancer317
- Fluorescent in situ hybridization318
- Genetic analysis of cancer318
- Comparative genomic hybridization in cancer diagnostics318
- Loss of heterozygosity319
- Digital karyotyping319
- Gene expression profiles predict chromosomal instability in tumors319
- PCR Techniques320
- Realtime quantitative PCR for diagnosis of cancer320
- Cold-PCR320
- Antibody-based diagnosis of cancer321
- Monoclonal antibodies for diagnosis of cancer321
- Recombinant antibodies as a novel approach to cancer diagnosis321
- Combined immunological and nucleic acid tests322
- Combination of MAbs and RT-PCR322
- Immunobead RT-PCR322
- Assays for determining susceptibility to cancer322
- Gene expression profiling in cancer322
- Microarrays for gene expression profiling in cancer323
- Serial analysis of gene expression (SAGE)323
- DNA tags for finding genes expressed in cancer324
- Suppression subtractive hybridization324
- Measurement of telomerase activity324
- Detection of cancer cells in blood of patients with solid tumors325
- Epithelial aggregate separation and isolation326
- Proteomic technologies for the molecular diagnosis of cancer327
- Proteomic technologies for tumor biomarkers327
- Affibodies as contrast agents for imaging in cancer327
- Aptamer-based technology for protein signatures of cancer cells328
- Aptamers for combined diagnosis and therapeutics of cancer328
- Automated image analysis of nuclear protein distribution329
- Laser capture microdissection in oncology329
- Layered expression scanning330
- Survivin and molecular diagnosis of cancer330
- Biochip/microarrays for cancer diagnosis330
- Role of DNA microarrays in gene expression profiling331
- Biochip detection of FHIT gene331
- Nanobiotechnology for early detection of cancer332
- Detection of nanoparticle self assembly in tumors by MRI332
- Differentiation between normal and cancer cells by nanosensors332
- Magnetic nanoparticle probes332
- Quantum dots for early detection of cancer333
- Molecular imaging of cancer333
- In vivo tumor illumination by adenoviral-GFP334
- PET for in vivo molecular diagnosis of cancer334
- Xenon-enhanced MRI334
- Optical systems for in vivo molecular imaging of cancer334
- Detection of micrometastases335
- Molecular diagnosis of cancers of various organs335
- Brain tumors336
- Molecular diagnostic methods for brain tumors336
- Glioblastoma multiforme336
- Circulating microvesicles as biomarkers of glioblastoma337
- Combination of neuroimaging and DNA microarray analysis in GBM337
- Medulloblastoma338
- Oligodendroglioma338
- Advantages and limitations of molecular diagnosis of brain tumors338
- Breast cancer338
- Breast cancer genes339
- Molecular diagnostic tests for breast cancer340
- Mouse ESC-based assays to evaluate mutations in BRCA2342
- Genomic profiles of breast cancer342
- Role of molecular diagnostics in management of breast cancer343
- Tests for prognosis of breast cancer347
- Prediction of recurrence in breast cancer for personalizing therapy348
- Cervical cancer350
- Colorectal cancer350
- Diagnosis of hereditary nonpolyposis colorectal cancer350
- Detection of familial adenomatous polyposis coli351
- Diagnosis of colorectal cancer from DNA in stools351
- Detection of circulating tumor cells in colorectal cancer352
- Minimally invasive screening for colorectal cancer352
- Guanylyl cyclase C tests for colorectal cancer352
- Early diagnosis of colorectal cancer from blood samples353
- Gastric cancer353
- Head and neck cancer353
- Hematological malignancies354
- Chromosome translocations354
- Flow cytometry in diagnosis of leukemia354
- Gene chip technology354
- Laboratory assessment of leukemia355
- Molecular probes356
- Minimal residual disease356
- Screening of gene mutations in chronic myeloproliferative diseases356
- Lung cancer357
- Melanoma359
- Ovarian cancer359
- Mutation of genes360
- Relevance of genetic testing to management of ovarian cancer360
- Serum biomarkers for early detection of ovarian cancer360
- Biomarkers of ovarian cancer360
- Concluding remarks on testing for ovarian cancer361
- Pancreatic cancer361
- Prostate cancer362
- Gene expression analysis of prostate cancer by microarrays362
- Huntingtin Interacting Protein 1363
- Integrative genomic and proteomic profiling of prostate cancer363
- LCM for diagnosis of prostate cancer363
- PCA3 gene detection in urine364
- PCR assay for assessing silencing of protein cadherin 13 gene364
- Prostate biopsy for detection of prostatic intraepithelial neoplasia365
- Screening of multiple SNPs for risk of prostate cancer365
- Semen testing for prostate cancer biomarkers365
- Serum-protein fingerprinting in prostate cancer366
- Thyroid cancer366
- Gene expression biomarkers of thyroid cancer367
- Multiple endocrine neoplasia type 2B as risk factor for thyroid cancer367
- miRNA expression profiling in thyroid cancer367
- Urinary bladder cancer368
- Role of molecular diagnostics in the management of cancer368
- Risk assessment and prevention of cancer368
- Role of molecular diagnosis in the design of future cancer therapies369
- Molecular classification of cancer369
- Determination of cancer prognosis370
- Prognosis by tumor classification370
- Prognosis by cancer gene expression370
- Selection of anticancer drugs based on molecular diagnosis370
- Integrated genome-wide analysis of cancer for diagnosis and therapy371
- Personalized therapy for cancer patients371
- Pharmacogenetics and cancer therapy371
- Molecular diagnostics as an aid to selection of cancer therapy372
- Drug resistance in cancer373
- Role of organizatons in molecular diagnosis of cancer373
- Role of NCI in molecular diagnosis of cancer373
- Molecular profiling of cancer373
- Cancer Genome Atlas374
- Cancer Genetic Markers of Susceptibility Project374
- Support for future research in molecular diagnosis of cancer375
- Role of the International Cancer Genome Consortium375
- Future prospects of molecular diagnosis of cancer376
- Companies involved in molecular diagnosis of cancer376
8. Molecular Diagnostics in Biopharmaceutical Industry & Healthcare 382
- Introduction382
- Molecular diagnostics in biopharmaceutical industry382
- Molecular diagnostic technologies and drug discovery382
- Molecular diagnostics and pharmacogenetics383
- Molecular toxicology384
- Gene expression studies385
- Toxicogenomics385
- Toxicoproteomics386
- Mitochondrial assays387
- MetaChip387
- Molecular diagnostics and pharmacogenomics388
- Applications molecular diagnostics in gene therapy389
- Use of PCR to study biodistribution of gene therapy vectors389
- PCR for verification of the transcription of DNA390
- In situ PCR for direct quantification of gene transfer into cells390
- Detection of retroviruses by reverse transcriptase (RT)-PCR390
- Assessment of safety issues of gene transfer390
- Quantitative PCR for monitoring the effectiveness of gene therapy390
- Use of FISH for analysis of adeno-associated viral vector integration390
- Monitoring of gene expression by green fluorescent protein391
- Detection of microbial contamination in biopharmaceutical manufacturing391
- Role of PCR in detecting contamination of biopharmaceuticals391
- Contamination of biopharmaceuticals with prions392
- DNA tagging for control and tracing of drug distribution channels392
- Molecular diagnostics for organ transplantation392
- Tissue typing392
- Commercial products for transplant molecular diagnostics394
- Post-cardiac transplant patient monitoring for rejection396
- Blood Transfusion Screening396
- Molecular tests for screening of blood supply for viruses397
- Commercial molecular diagnostic technologies for blood screening398
- Bridge Amplification Technology399
- COBAS AmpliScreen HCV and HIV Assays399
- INACTINE399
- NucliSens Extractor system399
- Pall' s enhanced Bacteria Detection System400
- PCR combined with algorithm method400
- Prions detection in human blood401
- PRISMR automated system401
- Procleix HIV-1/HCV Assay401
- West Nile virus detection in human blood402
- Limitations of molecular diagnostics for blood screening402
- Molecular epidemiology403
- Molecular epidemiology of genetic diseases403
- Monogenic versus polygenic disorders404
- Critical issues facing genetic epidemiology404
- Molecular epidemiology of infectious diseases404
- Methods and purposes404
- Emerging infections405
- Human vs. non-human infections405
- Genetics and susceptibility to infectious disease406
- Molecular epidemiology of cancer406
- Molecular epidemiology of p53 gene mutations407
- Molecular epidemiology of link between virus and cancer407
- Molecular epidemiology and cancer prevention407
- SNPs and molecular epidemiology407
- Molecular diagnostics for identification of food-borne pathogens407
- Introduction407
- Molecular diagnostic methods used in food-borne infections408
- Limitations of use of molecular probes in food analysis409
- Optical biosensor for detection of Listeria-contaminated foods409
- Companies with technologies for food pathogen detection410
- Transmissible spongiform encephalopathies (TSEs)411
- Molecular diagnosis of TSEs411
- Companies involved in developing molecular diagnostics for TSEs414
- Detection of genetically modified organisms in food415
- Molecular diagnostics for detection of doping in sports415
- Screening of synthetic glucocorticosteroids in human urine416
- Detection of gene doping416
- Role of molecular diagnostics in future healthcare416
- Translation of genomic research into genetic testing for healthcare417
- Molecular diagnostics and disease management417
- Role of genetic biomarkers in disease management418
- Role of molecular diagnostics in personalized medicine418
- Integrated healthcare418
- Screening418
- Early diagnosis419
- Prevention419
- Therapy based on molecular diagnosis419
- Monitoring of therapy419
- Advantages and limitations of integrated healthcare420
- Commercially available systems for integrated healthcare420
- Combination of diagnostics and therapeutics421
- Companion diagnostics421
- Companies involved in companion diagnostics421
- Point-of-care diagnosis423
- Technologies for point-of-care diagnosis424
- Biochips for point-of-care diagnosis425
- Companies developing point-of-care diagnosis426
- Advantages versus disadvantages of point-of-care diagnosis428
- The impact of molecular diagnostics on clinical laboratory practice428
9. Molecular Diagnostics in Forensic Medicine and Biological Warfare 430
- Application of molecular diagnostics in forensic medicine430
- Technologies430
- Extraction of DNA from forensic samples430
- Mitochondrial DNA (mtDNA) analysis431
- Polymorphic Alu insertions431
- Single Nucleotide Polymorphisms (SNP) analysis432
- Short tandem repeat (STR)432
- Fluorescent detection systems433
- ABO genotyping433
- DNA analysis for identification of ancient or historical specimens433
- Applications433
- Applications in criminology434
- Identification of remains of military personnel435
- Identification of remains of victims of mass disasters435
- Parentage testing436
- Gender determination437
- Companies developing molecular diagnostics for forensic science438
- Molecular detection of biological warfare agents439
- Introduction to biological warfare agents439
- Role of PCR in the diagnosis of biological warfare agents440
- Multiplex PCR microarray assay to detect bioterror pathogens in blood440
- Laboratory diagnosis of Anthrax441
- Challenges in diagnosis of biological warfare agents441
- US government efforts for detection of biological warfare agents442
- The US Army Medical Research Institute of Infectious Diseases442
- Homeland Security Advance Research Projects Agency443
- Commercial development of diagnostic devices for biological agents443
- Companies developing diagnostic devices for biological agents443
- Biodefence microarray446
- Identification of genetic markers of individual pathogens446
- Microbial Identification System based on OptiChip"!447
- Hand-Held Advanced Nucleic Acid Analyzer447
- Nanogen' s portable detection device447
- Nanode Array Sensor Microchips448
- MicroChemLab448
- BioThreat Alert Test Strip448
- Benchtop living cell biosensor449
- BioForce NanoArray sensor technology449
- QTL handheld biosensor449
- Analyte 2000 biosensor450
- Airborne bacterial spore detection technology450
- Destruction and detection of anthrax by lysin450
- Biosensor based on mass spectrometry of microorganisms' s RNA450
- Bead ARray Counter451
- ProteinChip-based detection of bioterroism agents451
- TIGER biosensor451
- The PathAlert™ Detection System452
- VereThreat"!452
- Concluding remarks about biodefense applications of diagnostics452
10. References 454
Tables
- Table 1 1: Landmarks in development of molecular technology and its
application to diagnosis23
- Table 1 2: Applications of molecular diagnostics42
- Table 2 1: Companies with products for nucleic acid isolation51
- Table 2 2: Some commercially available real-time PCR systems54
- Table 2 3: Applications of real-time PCR55
- Table 2 4: A selection of companies with commercially available FISH
diagnostics80
- Table 2 5: Selected companies with RNA diagnostic tests81
- Table 2 6: Companies involved in whole genome amplification89
- Table 2 7: Companies involved in sequencing92
- Table 2 8: Comparison of methods of identification of unknown DNA
sequences94
- Table 2 9: Classification of methods of gene expression analysis95
- Table 2 10: A selection of companies with gene expression technologies100
- Table 2 11: Companies involved in developing PNA diagnostics103
- Table 3 1: Applications of biochip technology in relation to molecular
diagnostics109
- Table 3 2: Companies developing whole genome chips/microarrays115
- Table 3 3: Companies involved in biochips for molecular diagnostics116
- Table 3 4: Companies developing microfluidic technologies120
- Table 3 5: Biosensor technologies with potential applications in molecular
diagnostics121
- Table 3 6: Important applications of biosensors131
- Table 3 7: Companies involved in application of biosensors in molecular
diagnostics131
- Table 3 8: Selected labels for nucleic acid detection133
- Table 3 9: Selected companies with fluorescence and chemiluminescence
products134
- Table 3 10: Companies involved in molecular beacon manufacture and
research136
- Table 3 11: Selected companies involved in molecular imaging143
- Table 3 12: Nanotechnologies with potential applications in molecular
diagnostics144
- Table 3 13: Companies developing nanomolecular diagnostics152
- Table 4 1: Applications of protein biochips/microarrays163
- Table 4 2: Companies involved in developing diagnostic applications of
protein biochips170
- Table 4 3: Disease-specific proteins in the cerebrospinal fluid of
patients172
- Table 5 1: Mutation detection technologies181
- Table 5 2: Technologies for SNP analysis188
- Table 5 3: A sampling of companies involved in technologies for SNP
genotyping198
- Table 5 4: Application of preimplantation genetic diagnosis in monogenic
disorders207
- Table 5 5: Companies involved in prenatal/preimplantation diagnostics209
- Table 5 6: CFTR genotyping in cystic fibrosis - companies and
technologies210
- Table 5 7: X-linked immunodeficiency disorders214
- Table 5 8: Genes that cause cardiovascular diseases220
- Table 5 9: Available molecular diagnostics for neurogenetic diseases228
- Table 5 10: Companies offering genetic screening tests directly to
consumers235
- Table 6 1: Molecular techniques for the diagnosis of infections237
- Table 6 2: Bacteria and fungi that can be detected by recombinant DNA
tests250
- Table 6 3: Viruses that can be detected by recombinant DNA methods261
- Table 6 4: Companies with molecular diagnostics for avian influenza virus
H5N1283
- Table 6 5: Companies developing POC tests for the diagnosis of
infections298
- Table 6 6: Selected companies involved in molecular diagnosis of
infections301
- Table 7 1: Estimated new cases of cancer in the US at most involved organs
- 2008303
- Table 7 2: Tumor suppressor genes, their chromosomal location, function,
and associated tumors304
- Table 7 3: Viruses linked to human cancer306
- Table 7 4: A classification of molecular diagnostic methods in cancer308
- Table 7 5: Desirable characteristics of biomarkers for cancer311
- Table 7 6: Approved monoclonal antibodies for cancer diagnosis320
- Table 7 7: Methods for comparison of gene-expression profilling in tumor
specimens322
- Table 7 8: Impact of in vivo molecular imaging of cancer on oncology
practice334
- Table 7 9: Companies developing cancer molecular diagnostics375
- Table 8 1: Applications of molecular diagnostics in the biopharmaceutical
industry381
- Table 8 2: Molecular diagnostic technologies for drug discovery382
- Table 8 3: Molecular diagnostic technologies used for pharmacogenetic
studies382
- Table 8 4: Companies with novel molecular toxicology technologies383
- Table 8 5: Applications of molecular diagnostics in gene therapy388
- Table 8 6: Companies involved in transplant molecular diagnostics393
- Table 8 7: Companies involved in molecular diagnostics of blood
transfusions397
- Table 8 8: Pathogenic bacteria in food and targets for molecular
diagnostic probes407
- Table 8 9: Companies involved in molecular diagnostics for food-borne
infections409
- Table 8 10: Testing for harmful prions in brain tissue from dead cattle411
- Table 8 11: Companies involved in developing molecular diagnostics for
TSEs413
- Table 8 12: Companies involved in companion diagnostics421
- Table 8 13: Applications of point-of-care diagnosis422
- Table 8 14: Companies developing point-of-care diagnostic tests425
- Table 9 1: Forensic and legal applications of molecular diagnostics432
- Table 9 2: Molecular technologies used for forensic applications437
- Table 9 3: Classification of biological and chemical agents used as
weapons of mass destruction438
- Table 9 4: Biological warfare agents that can be identified by PCR
methods439
- Table 9 5: Companies developing detection devices for biological warfare
agents443
Figures
- Figure 1 1: Relation of molecular diagnostics to other technologies43
- Figure 2 1: Rolling circle amplification technology63
- Figure 2 2: A schematic view of the Invader operating system71
- Figure 2 3: Principle of fluorescent in situ hybridization75
- Figure 2 4: Repli-G system of Qiagen90
- Figure 2 5: DNA sequencing process91
- Figure 2 6: Electrochemical detection of DNA105
- Figure 2 7: Elements of a Scorpions primer106
- Figure 3 1: Affymetrix GeneChip technology110
- Figure 3 2: Basic principle of a biosensor121
- Figure 3 3: Surface plasmon resonance (SPR) technology126
- Figure 6 1: Use of DNA chips in diagnosing microbial infections239
- Figure 6 2: High throughput DNA pyrosequencing for pathogen discovery242
Part II
11. Ethics, Patents and Regulatory issues 11
- Introduction11
- Ethical concerns about genetic diagnosis11
- Ethical guidelines for molecular diagnostics12
- Ethical and regulatory aspects of direct-to-consumer genetic services13
- US public attitudes about genetic testing15
- Genetic testing for susceptibility to adult-onset cancer15
- Ethics of preimplantation genetic diagnosis16
- Preimplantation genetic diagnosis to screen for hereditary diseases16
- PGD to test for susceptibiliy to cancer16
- PGD and stem cells17
- Genetic research on stored tissues17
- Informed consent in clinical trials of in vitro devices17
- Concluding remarks about ethical issues18
- Insurance underwriting and gene tests18
- Should genetic information be available to health insurers?18
- A need for the re-examination of current views19
- Genetic Information Nondiscrimination Act of US19
- Patents for molecular diagnostics20
- PCR patents20
- Patenting DNA sequences20
- US policy on gene patenting relevant to molecular diagnostics20
- The impact of disease gene patents on molecular diagnostics21
- Licensing problems associated with genetic testing21
- Role of the WHO in genetic testing standards22
- Regulatory issues in the US22
- Assay Migration Studies for In Vitro Diagnostic Devices22
- Assessment of diagnostic accuracy23
- Sensitivity and specificity23
- Documentation of diagnostic accuracy23
- Assessment of laboratory-developed tests used by Medicare recipients24
- Discovery of incidental findings on genetic screening25
- Evaluation of companion diagnostics/therapeutic for cancer25
- FDA regulation of multivariate index assays26
- FDA guidance for IVDs to detect pathogens27
- FDA guidelines for devices to detect and differentiate HPV27
- FDA' s Microarray Quality Control28
- FDA and point-of-care diagnosis28
- Genetic testing of rare disorders29
- Quality control of molecular diagnostic laboratory procedures29
- Quality control of point-of-care tests30
- Regulation of IVD by the FDA30
- Regulation of in vivo diagnostics by the FDA31
- Regulation of analytic-specific reagents32
- Regulatory aspects of FISH32
- Regulation of genetic testing32
- Role of the FDA in genetic testing32
- Regulatory issues concerning blood and plasma products33
- United States Diagnostics Standards33
- Regulation of in vitro diagnostics in the EU34
- EU regulations for testing of blood products34
- Regulation of genetic testing in EU34
- Evaluation of diagnostic laboratory tests in the UK35
- Pre-implantation genetic diagnosis in the UK35
12. Markets for Molecular Diagnostics 37
- Introduction37
- Methods for study of molecular diagnostic markets37
- The overall market for diagnostic technologies38
- Molecular diagnostic markets according to technologies38
- Marketing strategies according to technologies39
- Nucleic acid isolation market39
- Market for PCR-based tests39
- DNA sequencing market39
- Cytogenetic market40
- Market for FISH technologies40
- Biochip/microarray market40
- Biosensor market41
- Nanobiotechnology for molecular diagnostics41
- Markets for gene expression technologies41
- Reagents and other disposable laboratory materials41
- Market for immunochemistry diagnostic42
- Markets for tissue diagnostics42
- Molecular diagnostic markets according to therapeutic areas42
- Genetic disorders43
- Prenatal testing44
- Cancer44
- Potential markets for cancer diagnosis according to type of cancer45
- Infectious diseases45
- Sexually transmitted diseases46
- Hospital-acquired infections47
- Testing for HIV drug resistance48
- Potential markets for avian influenza diagnostics48
- Cardiovascular diseases48
- Neurological disorders49
- Food testing49
- Screening of blood for transfusion49
- Tissue typing for transplantation49
- Marketing opportunities according to geographic areas49
- Unmet needs in molecular diagnostics50
- Major market trends51
- Markets according to home-brew and FDA-approved tests51
- Decentralization of molecular diagnostics52
- Point-of-care testing52
- Development of personalized medicine53
- Cost of sequencing the human genome53
- Cost of genotyping53
- Marketing companion diagnostics for personalized medicine54
- Development of low-cost tests54
- Simplification of test procedures55
- Increasing role of proteomics in clinical diagnostics55
- Forensic and legal applications55
- Marketing strategies55
- Role of alliances in commercialization of molecular diagnostics56
- Acquisitions vs collaborations56
- Analysis of collaborations in molecular diagnostics59
- Licensing of the technologies60
- Strategies related to laboratory facilities and technologies60
- Strategies relevant to the healthcare system61
- Cost-Benefit studies61
- Genetic susceptibility testing61
- Preventive medicine strategies62
- Targeting treatable and common diseases62
- Information/education62
- Physician education62
- Patient education63
- European diagnostic information platform63
- Regulatory strategies64
- Merger of in vitro and in vivo diagnostics64
- Integration of diagnostics with therapeutics64
- Diagnostic applications in clinical trials64
- Prospects for development of new technologies65
- Drivers for the development of molecular diagnostics65
- Factors slowing the development of molecular diagnostics65
- Government support of research relevant to molecular diagnostics66
- Cost of sequencing the human genome66
- European projects for improving molecular diagnostics68
- European Consortium for developing new DNA analysis tools68
- EU project for improvement of IVD tools procedures69
- Genetic knowledge parks in the UK69
- Molecular diagnostic opportunities in defense against bioterrorism69
- Molecular diagnostics for food safety70
- POC diagnostics for the developing countries70
13. Companies involved in molecular diagnostics 71
- Introduction71
- Major players in molecular diagnostics71
- Profiles of selected companies72
- Collaborations418
Tables
- Table 12 1: Share of in vitro diagnostics in the global diagnostic market
2008-201838
- Table 12 2: Molecular diagnostics markets according to technologies from
2008-201838
- Table 12 3: Molecular diagnostics markets according to applications
2008-201842
- Table 12 4: Markets in 2008 for tests to screen healthy persons for
genetic disorders43
- Table 12 5: Markets in 2008 for molecular diagnostic tests for cancer44
- Table 12 6: Molecular diagnostic markets for selected cancers 2008-201845
- Table 12 7: Markets value in 2008 for molecular diagnostic screening for
infections46
- Table 12 8: Future markets for HAI diagnostics 2008-201347
- Table 12 9: Molecular diagnostic markets according to geographical areas
2008-201850
- Table 12 10: Molecular diagnostic markets according to home-brew and
approved tests51
- Table 12 11: Marketing strategies for molecular diagnostics55
- Table 12 12: Takeovers of molecular diagnostic companies56
- Table 12 13: Advantages of the integration of diagnostics with
therapeutics63
- Table 13 1: Top ten players in molecular diagnostics71
- Table 13 2: Collaborations of companies in molecular diagnostics417
Figures
- Figure 12 1: Unmet needs in applications of molecular diagnostics51
- Figure 12 2: Proportion of various areas in molecular diagnostic
collaborations59
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