Table of Contents
0. Executive Summary 21
1. Introduction 23
- Definitions and scope of the subject 23
- Historical evolution of molecular diagnostics 23
- Molecular biology relevant to molecular diagnostics 24
- Genome 24
- DNA 24
- DNA polymerases 25
- Restriction endonucleases 25
- DNA methylation 25
- RNA 26
- RNA polymerases 26
- MicroRNAs 27
- DNA transcription 27
- Chromosomes 27
- Telomeres 28
- Mitochondrial DNA 28
- Genes 29
- The genetic code 29
- Gene expression 29
- DNA sequences 30
- Junk DNA 30
- Single nucleotide polymorphisms 30
- Genotype and haplotypes 31
- Replication of the DNA helix 31
- Proteins 32
- Proteomics 32
- Monoclonal antibodies 32
- Aptamers 32
- Basics of molecular diagnostics 33
- Tracking DNA: the Southern blot 33
- Pulsed-field gel electrophoresis 34
- DNA Probes 34
- The polymerase chain reaction 34
- Basic Principles of PCR 34
- Target selection 35
- Detection of amplified DNA 35
- Impact of human genome project on molecular diagnostics 36
- Genetic variations in the human genome 36
- Insertions and deletions in the human genome 36
- Large scale variation in human genome 37
- Variation in copy number in the human genome 37
- Structural variations in the human genome 38
- Mapping and sequencing of structural variation from human genomes 39
- 1000 Genomes Project 39
- Human Variome Project 40
- Systems biology approach to molecular diagnostics 41
- Biomarkers 41
- Applications of molecular diagnostics 42
2. Molecular Diagnostic Technologies 45
- Introduction 45
- DNA extraction 45
- Transrenal DNA 45
- Sample preparation 46
- Pressure Cycling Technology 46
- Membrane immobilization of nucleic acids 46
- Automation of sample preparation in molecular diagnostics 47
- ABI PRISM 6700 Automated Nucleic Acid Workstation 47
- BioRobot technology 47
- COBAS AmpliPrep System 47
- GENESIS FE500 Workcell 47
- GeneMole 48
- PCR BioCube 48
- QIAsymphony 48
- Tigris instrument system 48
- Techniques for sample preparation that are suitable for automation 49
- Xtra Amp Genomic DNA Extraction 49
- Extraction of DNA from paraffin sections 49
- Dynabead technology 49
- Pressure Cycling Technology 50
- SamPrep 50
- Use of magnetic particles for automation in genome analysis 50
- Companies involved in nucleic acid isolation 51
- Novel PCR methods 52
- Addressing limitations of PCR 52
- Real-time PCR systems 52
- Dyes used in real-time PCR 53
- Commercially available real-time PCR systems 54
- LightCycler PCR system 54
- LightUp probes based on real-time PCR 55
- Applications of real-time PCR 55
- Limitations of real-time PCR 56
- Improving the reliability of low level DNA analysis by real-time PCR 56
- Guidelines for real-time quantitative PCR 56
- Future applications of real-time Q-PCR 57
- Reverse transcriptase (RT)-PCR 57
- Standardized reverse transcriptase PCR 58
- Single cell PCR 58
- LATE-PCR 58
- Cold-PCR 59
- AmpliGrid-System 59
- Digital PCR 59
- Long and accurate PCR 60
- Combined PCR-ELISA 60
- Monitoring of gene amplification in molecular diagnostics 61
- Non-PCR nucleic acid amplification methods 61
- Linked Linear Amplification 61
- Transcription mediated amplification 61
- Rapid analysis of gene expression 62
- WAVE nucleic acid fragment analysis system 62
- DNA probes with conjugated minor groove binder 63
- Rolling circle amplification technology 63
- Gene-based diagnostics through RCAT 64
- RCAT-immunodiagnostics 65
- RCAT-biochips 65
- RCAT-pharmacogenomics 65
- Circle-to-circle amplification 66
- Ramification amplification method 66
- Single Primer Isothermal Amplification 66
- Isothermal reaction for amplification of oligonucleotides 67
- ICAN (Isothermal and Chimeric primer-initiated Amplification of Nucleic
Acids) 67
- Technologies for signal amplification 67
- 3 DNA dendrimer signal amplification 67
- Hybridization signal amplification method 68
- Signal mediated amplification of RNA technology 69
- Invader assays 70
- Hybrid Capture technology 71
- Branched DNA test 72
- Tyramide signal amplification 72
- Non-enzymatic signal amplification technologies 72
- Direct molecular analysis without amplification 73
- Direct detection of dsDNA 74
- Multiplex assays 75
- Fluorescent in situ hybridization 75
- Modifications of FISH 77
- Direct visual in situ hybridization 77
- Direct labeled Satellite FISH probes 77
- Comparative genomic hybridization 78
- Primed in situ labeling 78
- Interphase FISH 78
- FISH with telomere-specific probes 78
- Multicolor FISH 79
- Automation of FISH 79
- Companies involved in FISH diagnostics 79
- RNA diagnostics 80
- Branched-chain DNA assay for measurement of RNA 81
- Cycling probe technology 82
- Invader RNA assays 82
- Linear RNA amplification 82
- Non-isotopic RNase cleavage assay 83
- Nucleic acid sequence-based amplification 83
- Q Beta replicase system 85
- Solid Phase Transcription Chain Reaction 85
- Transcriptome analysis 85
- Visualization of mRNA expression in vivo 86
- MicroRNA diagnostics 86
- Real-time PCR for expression profiling of miRNAs 86
- Microarray vs quantitative PCR foro measuring miRNAs 87
- Use of LNA to explore miRNA 87
- Nuclease Protection Assay to measure miRNA expression 88
- Microarrays for analysis of miRNA gene expression 88
- Modification of in situ hybridization for detection of miRNAs 89
- Whole genome amplification 89
- Companies that provide technologies for whole genome amplification 89
- QIAGEN' s Repli-G system 90
- GenomePlex™ Whole Genome Amplification 90
- DNA sequencing 91
- Companies involved in sequencing 92
- Applications of next generation sequencing in molecular diagnostics 93
- Genome-wide approach for chromatin mapping 93
- Mitochondrial sequencing 93
- Identification of unknown DNA sequences 94
- Optical mapping 94
- Gene expression analysis 95
- Gene expression profiling on whole blood samples 95
- Gene expression patterns of white blood cells 96
- Gene expression profiling based on alternative RNA splicing 96
- MAUI (MicroArray User Interface) hybridization 97
- Monitoring in vivo gene expression by molecular imaging 97
- Serial analysis of gene expression (SAGE) 97
- Single-cell gene expression analysis 97
- T cell receptor expression analysis 98
- Tangerine"! expression profiling 98
- Whole genome expression array 99
- Ziplex"! system 99
- Companies involved in gene expression analysis 100
- Peptide nucleic acid technology 101
- Use of PNA with fluorescence in situ hybridization 101
- PNA and PCR 102
- Use of PNA with biosensors 102
- PNA-based PD-loop technology 103
- PNA-DNA hybrid quadruplexes 103
- Companies Involved in PNA Diagnostics 103
- Locked nucleic acids 104
- Electrochemical detection of DNA 104
- Mediated nucleic acid oxidation 105
- Detection of hybridized nucleic acid with cyclic voltametry 105
- Electrochemical detection based on Toshiba' s CMOS technology 106
- Concluding remarks on electrochemical DNA detection 106
- Scorpions"! technology 106
- The Scorpions reaction 106
- Applications of Scorpion 107
3. Biochips, Biosensors, and Molecular Labels 109
- Introduction to biochip technology 109
- Applications of biochips in diagnostics 109
- GeneChip 110
- GeneChip Human Genome Arrays 111
- AmpliChip CYP450 111
- Electronic detection of nucleic acids on microarrays 111
- Microchip capillary electrophoresis 112
- Strand displacement amplification on a biochip 112
- Rolling circle amplification on DNA microarrays 112
- Fast PCR biochip 112
- Multiplex microarray-enhanced PCR for DNA analysis 113
- Multiplexed Molecular Profiling 113
- Universal DNA microarray combining PCR and ligase detection reaction 114
- Genomewide association scans 114
- Whole genome chips/microarrays 114
- Transposon insertion site profiling chip 115
- Standardizing the microarrays 115
- Companies involved in developing biochip technology for diagnostics 116
- Future of biochip technology for molecular diagnostics 117
- Microfluidic chips 117
- Fish-on-chip 118
- Lab-on-a-chip 118
- LabCD 118
- Micronics' microfluidic technology 119
- Microfluidic automated DNA analysis using PCR 119
- Microfluidic chips integrated with PET 119
- Companies developing microfluidic technologies 120
- Biosensor technologies 120
- Classification of biosensor technologies 121
- DNA-based biosensors 122
- DNA hybridization biosensor chips 122
- PCR-free DNA biosensor 122
- DNA based biosensor to detects metallic ions 123
- Genetically engineered B lymphocytes 123
- Biosensors immunoassays 123
- PNA (peptide nucleic acid)-based biosensors 124
- Protein-based biosensors 124
- Antibody biosensors 124
- Cell-based biosensors (cytosensors) 124
- Multicell biosensors 125
- Microbial biosensors 125
- Optical biosensors 126
- Surface plasmon resonance technology 126
- Label-free optical biosensor 127
- Microsensors using with nano/microelectronic communications technology 127
- Electrochemical sensors 127
- Enzyme electrodes for biosensing 127
- Conductometric sensors 128
- Electrochemical genosensors 128
- Electrochemical nanobiosensor 128
- Bioelectronic sensors 129
- Phototransistor biochip biosensor 129
- Ribozyme-based sensors 129
- RiboReporters 130
- Concluding remarks and future prospects of biosensor technology 130
- Companies developing biosensors for molecular diagnostics 131
- Molecular labels and detection 132
- Detection technologies for molecular labels 133
- Fluorescence and chemiluminescence 133
- Fluorescence technologies for label detection 134
- Companies with fluorescence and chemiluminescence products 134
- Molecular beacons 135
- The Green fluorescent protein 136
- Multiophoton detection radioimmunoassay 137
- Multi-pixel photon counter 137
- Enzyme labels and detection by fluorescence 137
- Phase-sensitive flow cytometry 138
- Microtransponder-based DNA diagnostics 138
- Laboratory Multiple Analyte Profile 139
- Multiple labels 139
- Protein-DNA chimeras for detection of small numbers of molecules 140
- Single molecule detection 140
- Atomic force microscopy 141
- Capillary electrophoresis 141
- Confocal laser scanning 141
- Spectrally resolved fluorescence lifetime imaging microscopy 141
- Molecular imaging 142
- Basic research in molecular imaging 142
- Devices for molecular imaging 143
- Molecular imaging in clinical practice 143
- Challenges and future prospects of molecular imaging 143
- Companies involved in molecular imaging 143
- Nanobiotechnology for molecular diagnostics 144
- Magnetic nanoparticles 145
- Gold nanoparticles 146
- Quantum dot technology 146
- Nanotechnology on a chip 147
- Nanogen' s NanoChip 148
- Fullerene photodetectors for chemiluminescence detection on microfluidic
chip 148
- Diagnostics based on nanopore technology 148
- Nanosensors 148
- Quartz nanobalance biosensor 149
- PEBBLE nanosensors 149
- Nanosensors for glucose monitoring 149
- Cantilever arrays 150
- Resonance Light Scattering technology 150
- DNA nanomachines for molecular diagnostics 151
- Nanobarcodes technology for molecular diagnostics 151
- Qdot nanobarcode for multiplexed gene expression profiling 152
- Role of nanobiotechnology in improving molecular diagnostics 152
- Companies involved in nanomolecular diagnostics 152
- Concluding remarks about nanodiagnostics 155
- Future prospects of nanodiagnostics 155
4. Proteomic Technologies for Molecular Diagnostics 157
- Introduction 157
- Proteomic technologies 157
- Biomarkers of disease 157
- Proteomic tools for biomarkers 157
- Search for biomarkers in body fluids 158
- Captamers with proximity extension assay for proteins 158
- Cyclical amplification of proteins 158
- Detection of misfolded proteins by ELISA with exponential signal
amplification 159
- Diagnostics based on designed repeat proteins 159
- Differential Peptide Display 159
- Light-switching excimer probes 160
- MALDI-TOF Mass Spectrometry 160
- Molecular beacon aptamer 161
- Molecular beacon assay 161
- Proteomic patterns 161
- Real-time PCR for protein quantification 163
- Protein biochip technologies 163
- ProteinChip 164
- LabChip for protein analysis 165
- TRINECTIN proteome chip 165
- Protein chips for antigen-antibody interactions molecular diagnostics 165
- Microfluidic devices for proteomics-based diagnostics 166
- Nanotechnology-based protein biochips/microarrays 166
- Nanoparticle protein chip 166
- Protein nanobiochip 166
- Protein biochips based on fluorescence planar wave guide technology 167
- New developments in protein chips/microarrays 167
- Antibody microarrays 168
- Aptamer-based protein biochip 168
- Multiplexed Protein Profiling on Microarrays 168
- Proteomic pattern analysis 169
- Single molecule array 169
- Viral protein chip 169
- Commercial development of protein chips for molecular diagnostics 170
- Proteome Identification Kit 171
- Laser capture microdissection (LCM) 171
- LCM technology 171
- Applications of LCM in molecular diagnostics 172
- Proteomic diagnosis of CNS disorders 172
- Cerebrospinal fluids tests based on proteomics 172
- Urine tests for CNS disorders based on proteins in urine 173
- Diagnosis of CNS disorders by examination of proteins in the blood 173
- Diagnosis of CNS disorders by examination of proteins in tears 174
- Role of proteomics in the diagnosis of Alzheimer' s disease 175
- Role of proteomics in the diagnosis of Creutzfeldt-Jakob disease 175
- Future prospects of use of proteomics for diagnosis of CNS disorders 175
- Concluding remarks on the use of proteomics in diagnostics 175
5. Molecular Diagnosis of Genetic Disorders 177
- Introduction 177
- Cytogenetics 178
- FISH with probes to the telomeres 178
- Single copy FISH probes 178
- Comparative genomic hybridization 179
- Use of biochips in genetic disorders 179
- Representational oligonucleotide microarray analysis 180
- SignatureChipR-based diagnostics for cytogenetic abnormalities 180
- Diagnosis of genomic rearrangements by multiplex PCR 180
- Quantitative fluorescent PCR 180
- Mutation detection technologies 181
- PCR-based methods for mutation detection 182
- Cleavase Fragment Length Polymorphism 182
- Direct dideoxy DNA sequencing 182
- Digital Genetic Analysis (DGA) 182
- Fluorescence-based directed termination PCR 183
- Heteroduplex analysis 183
- Restriction fragment length polymorphism 184
- Single-stranded conformation polymorphism (SSCP) analysis 184
- TaqMan real-time PCR 184
- Non-PCR methods for mutation detection 185
- Arrayed primer extension 185
- BEAMing (beads, emulsion, amplification, and magnetics) 185
- ELISA-protein truncation test 185
- Enzymatic mutation detection 186
- Specific anchor nucleotide incorporation 186
- Conversion analysis for mutation detection 186
- Biochip technologies for mutation detection 187
- Combination of FISH and gene chips 187
- Haplotype Specific Extraction 188
- Technologies for SNP analysis 188
- DNA sequencing 189
- Electrochemical DNA probes 189
- Use of NanoChip for detection of SNPs 190
- Single base extension-tag array 190
- Laboratory Multiple Analyte Profile 190
- SNP genotyping with gold nanoparticle probes 191
- PCR-CTPP (confronting two-pair primers) 191
- Peptide nucleic acid probes for SNP detection 191
- SNP genotyping on a genome-wide amplified DOP-PCR template 191
- Pyrosequencing 192
- Reversed enzyme activity DNA interrogation test 192
- Smart amplification process version 2 193
- Zinc finger proteins 193
- UCAN method (Takara Biomedical) 193
- Biochip and microarray-based detection of SNPs 194
- SNP genotyping by MassARRAY 194
- Electronic dot blot assay 194
- Biochip combining BeadArray and ZipCode technologies 195
- SNP-IT primer-extension technology 195
- OmniScan SNP genotyping 195
- Affymetrix SNP genotyping array 196
- Concluding remarks on SNP genotyping 196
- Limitations of SNP in genetic testing 196
- Haplotyping versus SNP genotyping 197
- Determination of copy number variations 197
- Companies involved in developing technologies/products for SNP analysis
197
- Prenatal DNA diagnosis 199
- Amniocentesis 199
- Chorionic villus sampling 199
- Separating fetal cells in maternal blood for genetic diagnosis 199
- Antenatal screening for Down' s syndrome 200
- Fetal DNA in maternal blood 200
- Molecular methods for prenatal diagnosis 201
- aCGH for prenatal diagnosis 201
- BAC HD Scan test 201
- FISH for prenatal diagnosis 202
- PCR for prenatal diagnosis 202
- Plasma DNA sequencing to detect fetal chromosomal aneuploidies 202
- In vivo gene expression analysis of the living human fetus 203
- Noninvasive prenatal diagnosis of monogenic diseases 203
- Digital relative mutation dosage 203
- Massively parallel plasma DNA sequencing 203
- Applications of prenatal diagnosis 204
- Diagnosis of congenital infections 205
- Diagnosis of eclampsia 205
- Use of transrenal DNA for prenatal testing 205
- Preimplantation genetic diagnosis 206
- Technologies for preimplantation genetic diagnosis (PGD) 206
- PCR for preimplantation genetic diagnosis 206
- FISH for preimplantation genetic diagnosis 206
- Microarrays for preimplantation genetic diagnosis 207
- Conditions detected by preimplantation genetic diagnosis 207
- The future of preimplantation genetic diagnosis 208
- Companies involved in prenatal/preimplantation diagnosis 209
- Cystic fibrosis 209
- Detection of CFTR gene mutations 210
- CFTR technologies of various companies 210
- Genzyme' s CF gene sequencing 211
- CF Plus™ Tag-It Cystic Fibrosis Kit 211
- Asuragen' s bead array test 212
- The Ambry CF Test 212
- Biochip for CF diagnosis 212
- Identification of CF variants by PCR/Oligonucleotide Ligation Assay 213
- MassARRAYR system for high-throughput CFTR testing 213
- Serum proteomic signature for CF using antibody microarrays 213
- Guidelines for genetic screening for CF 213
- Congenital adrenal hyperplasia 214
- Primary immunodeficiencies 214
- Hematological disorders 215
- Hemoglobinopathies 215
- Sickle cell anemia 215
- Thalassemia 216
- Paroxysmal nocturnal hemoglobinuria 216
- Hemophilia 217
- Hereditary hemochromatosis 217
- Polycystic kidney disease 217
- Hereditary metabolic disorders 218
- Lesch-Nyhan Syndrome 218
- Gaucher' s Disease 218
- Acute Intermittent Porphyria 219
- Phenylketonuria 219
- Hereditary periodic fever 219
- Achondroplasia 219
- Molecular diagnosis of cardiovascular disorders 220
- Coronary Heart Disease 221
- Cardiomyopathy 221
- Familial Hypertrophic Cardiomyopathy 222
- Idiopathic dilated cardiomyopathy 222
- Cardiac Arrhythmias 222
- Long Q-T Syndrome 222
- Familial atrial fibrillation 223
- Idiopathic ventricular fibrillation 223
- Congestive heart failure 223
- Hypertension 223
- Disturbances of blood lipids 224
- Familial dyslipoproteinemias 224
- Hypercholesterolemia 224
- Thrombotic disorders 225
- Factor V Leiden mutation 225
- Pulmonary embolism 225
- Molecular diagnosis of eye diseases 226
- Molecular diagnosis of retinitis pigmentosa 226
- Genetic screening for glaucoma 226
- Role of molecular diagnostics in rheumatoid arthritis 227
- Molecular diagnosis of neurogenetic disorders 227
- Alzheimer' s disease 229
- Down syndrome 229
- Parkinson' s disease 230
- Spinal muscular atrophy 231
- Duchenne and Becker muscular dystrophy 231
- Triple repeat disorders 231
- Huntington disease 232
- Fragile X syndrome 232
- Charcot-Marie Tooth disease 233
- Hereditary neuropathy with liability to pressure palsies 233
- eNOS gene polymorphisms as predictor of cerebral aneurysm rupture 233
- Mitochondrial disorders affecting the nervous system 234
- Genetic testing for disease predisposition 234
- Direct-to-consumer genetic tests 235
6. Molecular Diagnosis of Infections 237
- Introduction 237
- Molecular techniques for the diagnosis of infections 237
- Antibody-enhanced microplate hybridization assays 238
- Biosensors for detection of microorganisms 238
- Ibis T5000"! Biosensor System 238
- DNA enzyme immunoassay 239
- DNA biochip/microarray in diagnosis of infections 239
- DNA-based typing methods 240
- Restriction fragment length polymorphism analysis 240
- Ribotyping 240
- Random amplified polymorphic DNA 240
- Combinatorial DNA melting assay 240
- Electrochemical detection of pathogens 241
- Ligase chain reaction 241
- Mass spectrometry for microbial identification 241
- Metagenomic pyrosequencing 241
- Multiplex PCR for detection of infections 243
- LightCyclerR SeptiFast Test 243
- VYOOR Sepsis Test 243
- Dual priming oligonucleotide for multiplex PCR 244
- NASBA for detection of microorganisms 244
- Nucleic acid probes 244
- Neutrophil CD11b expression as a diagnostic marker 245
- Optical Mapping 245
- PNA-FISH for diagnosis of infections 245
- Quantitative reverse-transcription PCR for bacterial diagnostics 246
- Rupture event scanning 246
- Real-time single-molecule imaging of virus particles 246
- Single-strand conformational polymorphism 246
- SmartGene platform for identifying pathogens based on genetic sequences
247
- Tessera array technology 247
- Applications, advantages and limitations of molecular diagnostics 247
- Molecular diagnostics versus other microbial detection technologies 247
- Advantages of nucleic acid-based diagnostics in infections 248
- Drawbacks of nucleic acid-based diagnostics in infections 248
- Nanotechnology for detection of infectious agents 249
- Bacterial and fungal infections 249
- Mycobacterium tuberculosis 251
- Conventional diagnosis of tuberculosis 251
- Microscopic Observation Drug Susceptible Assay for tuberculosis 251
- Molecular diagnostics for tuberculosis 252
- Combined tuberculin testing and ELISpotPLUS assay 253
- Biomarkers for tuberculosis 254
- Diagnosis of drug-resistant M. tuberculosis infection 254
- Cost-effectiveness of PCR in tuberculosis screening 255
- Other mycobacteria 255
- Chlamydial infections 255
- Neisseria gonorrhoeae 257
- Bacteria associated with bacterial vaginosis 257
- Streptococcal infections 257
- Group B Streptococci 257
- Streptococcus pyogenes and Streptococcus dysgalactiae 258
- Pseudomonas aeruginosa 258
- Helicobacter pylori 259
- Lyme disease 259
- Mycoplasmas 260
- Fungal infections 260
- Viral infections 261
- HIV/AIDS 262
- Diagnosis of HIV 262
- Neonatal screening of infants of HIV-positive mothers 263
- Screening of cadaveric tissue donors 263
- Detection of HIV provirus 263
- Resolution of indeterminate Western blot 263
- Global Surveillance of HIV-1 genetic variations 264
- Genotyping for drug-resistance in HIV 264
- Phenotyping as predictor of drug susceptibility/resistance in HIV 265
- Tests used for quantification of HIV 266
- Conclusions about HIV genotyping 266
- Hepatitis viruses 267
- Hepatitis A virus 267
- Hepatitis B virus 268
- Hepatitis C virus 268
- Detection and quantification of HCV RNA 269
- Quantification of HCV RNA levels as a guide to antiviral therapy 270
- Electrochemical DNA chip for diagnosis of HCV 270
- HCV Genotyping as a guide to therapy 270
- Enteroviruses 271
- Adenoviruses 272
- Rhinoviruses 272
- Herpes viruses 272
- Herpes simplex virus 272
- Genital and neonatal herpes simplex 273
- Human cytomegalovirus infections 273
- Epstein-Barr virus 273
- Human papilloma virus 274
- Molecular diagnostics for HPV 274
- Detection of encephalitis viruses 275
- West Nile and St. Louis encephalitis 275
- Venezuelan equine encephalitis virus 275
- Protozoal infections 276
- Amebiasis 276
- Cryptosporidium parvum 276
- Malaria 276
- Neurocysticercosis 277
- Pneumocystis carinii 277
- Toxoplasmosis 277
- Infections of various systems 278
- CNS infections 278
- Molecular diagnosis in bacterial meningitis 278
- Molecular diagnosis in herpes simplex encephalitis 278
- Diagnosis of transmissible spongiform encephalopathies 279
- Molecular diagnosis of respiratory viruses 280
- SARS-associated coronavirus 280
- Influenza viruses 281
- Avian influenza 283
- H1N1 influenza 286
- Gastrointestinal infections 288
- Periodontal infections 289
- Diagnosis of urinary infections by a biosensor 290
- Role of molecular diagnostics in septicemia 290
- Limitations and needs of diagnostics for infections 291
- Differentiation between live and antibiotic-killed bacteria 291
- Cell-based methods for identifying pathogenic microorganisms 292
- Cell-based virus assays 292
- Cell-based detection of host response to infection 292
- Role of molecular diagnostics in hospital acquired infections 292
- Detection of hospital-acquired bacterial infections 293
- Detection of methicillin-resistant S. aureus 293
- Detection of vancomycin-resistant enterococci 294
- Detection of hospital-acquired C. difficile 294
- Bacterial genome sequencing in antimicrobial resistance 294
- Detection of hospital-acquired viral infections 295
- Molecular diagnosis of BK virus 295
- Diagnosis of hospital-acquired rotavirus gastroenteritis 295
- Molecular diagnostics and the microbiome 296
- Human Microbiome Project 296
- Application of metagenomics to study of the microbiome 296
- MicroBiome Analysis Center 297
- Concluding remarks and future prospects of diagnosis of infections 297
- Rapid point-of-care diagnosis of infection 298
- Diagnosis of viruses using protein fingerprinting 300
- QIAplex PCR multiplex technology 300
- Companies involved in molecular diagnosis of infectious diseases 300
7. Molecular Diagnosis of Cancer 303
- Introduction 303
- Cancer Genetics 303
- Oncogenes 303
- Tumor Suppressor Genes 304
- p53 305
- p16 305
- Viruses and cancer 306
- Detecting viral agents in cancer 306
- Conventional cancer diagnosis 307
- Molecular techniques for cancer diagnosis 308
- Genome analysis at the molecular level 309
- Mutation detection at molecular level 310
- Expression profiling of tumor cells sorted by flow cytometry 310
- MicroRNA expression profiling to classify human cancers 310
- Biomarkers in cancer 311
- Circulating nucleosomes in serum of cancer patients 311
- Detection of DNA methylation 312
- eTag assay system for cancer biomarkers 314
- HAAH as a biomarker for cancer 314
- LigAmp for detection of gene mutations in cancer 314
- Mitochondrial DNA as a cancer biomarker 315
- Oncoproteins as biomarkers for cancer 315
- Sequencing-based approaches for detection of cancer biomarkers 316
- Molecular fingerprinting of cancer 316
- Fluorescent in situ hybridization 317
- Genetic analysis of cancer 317
- Comparative genomic hybridization in cancer diagnostics 317
- Loss of heterozygosity 318
- Digital karyotyping 318
- Gene expression profiles predict chromosomal instability in tumors 318
- PCR Techniques 319
- Realtime quantitative PCR for diagnosis of cancer 319
- Cold-PCR 319
- Antibody-based diagnosis of cancer 320
- Monoclonal antibodies for diagnosis of cancer 320
- Recombinant antibodies as a novel approach to cancer diagnosis 320
- Combined immunological and nucleic acid tests 321
- Combination of MAbs and RT-PCR 321
- Immunobead RT-PCR 321
- Assays for determining susceptibility to cancer 321
- Gene expression profiling in cancer 321
- Microarrays for gene expression profiling in cancer 322
- Serial analysis of gene expression (SAGE) 322
- DNA tags for finding genes expressed in cancer 323
- Suppression subtractive hybridization 323
- Measurement of telomerase activity 323
- Detection of cancer cells in blood of patients with solid tumors 324
- Epithelial aggregate separation and isolation 325
- Proteomic technologies for the molecular diagnosis of cancer 326
- Proteomic technologies for tumor biomarkers 326
- Affibodies as contrast agents for imaging in cancer 326
- Aptamer-based technology for protein signatures of cancer cells 327
- Aptamers for combined diagnosis and therapeutics of cancer 327
- Automated image analysis of nuclear protein distribution 328
- Laser capture microdissection in oncology 328
- Layered expression scanning 329
- Survivin and molecular diagnosis of cancer 329
- Biochip/microarrays for cancer diagnosis 329
- Role of DNA microarrays in gene expression profiling 330
- Biochip detection of FHIT gene 330
- Nanobiotechnology for early detection of cancer 331
- Detection of nanoparticle self assembly in tumors by MRI 331
- Differentiation between normal and cancer cells by nanosensors 331
- Magnetic nanoparticle probes 331
- Quantum dots for early detection of cancer 332
- Molecular imaging of cancer 332
- In vivo tumor illumination by adenoviral-GFP 333
- PET for in vivo molecular diagnosis of cancer 333
- Xenon-enhanced MRI 333
- Optical systems for in vivo molecular imaging of cancer 333
- Detection of micrometastases 334
- Molecular diagnosis of cancers of various organs 334
- Brain tumors 335
- Molecular diagnostic methods for brain tumors 335
- Glioblastoma multiforme 335
- Circulating microvesicles as biomarkers of glioblastoma 336
- Combination of neuroimaging and DNA microarray analysis in GBM 336
- Medulloblastoma 337
- Oligodendroglioma 337
- Advantages and limitations of molecular diagnosis of brain tumors 337
- Breast cancer 337
- Breast cancer genes 338
- Molecular diagnostic tests for breast cancer 339
- Mouse ESC-based assays to evaluate mutations in BRCA2 341
- Genomic profiles of breast cancer 341
- Role of molecular diagnostics in management of breast cancer 342
- Tests for prognosis of breast cancer 346
- Prediction of recurrence in breast cancer for personalizing therapy 347
- Cervical cancer 349
- Colorectal cancer 349
- Diagnosis of hereditary nonpolyposis colorectal cancer 349
- Detection of familial adenomatous polyposis coli 350
- Diagnosis of colorectal cancer from DNA in stools 350
- Detection of circulating tumor cells in colorectal cancer 351
- Minimally invasive screening for colorectal cancer 351
- Guanylyl cyclase C tests for colorectal cancer 351
- Early diagnosis of colorectal cancer from blood samples 352
- Gastric cancer 352
- Head and neck cancer 352
- Hematological malignancies 353
- Chromosome translocations 353
- Flow cytometry in diagnosis of leukemia 353
- Gene chip technology 353
- Laboratory assessment of leukemia 354
- Molecular probes 355
- Minimal residual disease 355
- Screening of gene mutations in chronic myeloproliferative diseases 355
- Lung cancer 356
- Melanoma 358
- Ovarian cancer 358
- Mutation of genes 359
- Relevance of genetic testing to management of ovarian cancer 359
- Serum biomarkers for early detection of ovarian cancer 359
- Biomarkers of ovarian cancer 359
- Concluding remarks on testing for ovarian cancer 360
- Pancreatic cancer 360
- Prostate cancer 361
- Gene expression analysis of prostate cancer by microarrays 361
- Huntingtin Interacting Protein 1 362
- Integrative genomic and proteomic profiling of prostate cancer 362
- LCM for diagnosis of prostate cancer 362
- PCA3 gene detection in urine 363
- PCR assay for assessing silencing of protein cadherin 13 gene 363
- Prostate biopsy for detection of prostatic intraepithelial neoplasia 364
- Screening of multiple SNPs for risk of prostate cancer 364
- Semen testing for prostate cancer biomarkers 364
- Serum-protein fingerprinting in prostate cancer 365
- Thyroid cancer 365
- Gene expression biomarkers of thyroid cancer 366
- Multiple endocrine neoplasia type 2B as risk factor for thyroid cancer 366
- miRNA expression profiling in thyroid cancer 366
- Urinary bladder cancer 367
- Role of molecular diagnostics in the management of cancer 367
- Risk assessment and prevention of cancer 367
- Role of molecular diagnosis in the design of future cancer therapies 368
- Molecular classification of cancer 368
- Determination of cancer prognosis 369
- Prognosis by tumor classification 369
- Prognosis by cancer gene expression 369
- Selection of anticancer drugs based on molecular diagnosis 369
- Integrated genome-wide analysis of cancer for diagnosis and therapy 370
- Personalized therapy for cancer patients 370
- Pharmacogenetics and cancer therapy 370
- Molecular diagnostics as an aid to selection of cancer therapy 371
- Drug resistance in cancer 372
- Role of organizatons in molecular diagnosis of cancer 372
- Role of NCI in molecular diagnosis of cancer 372
- Molecular profiling of cancer 372
- Cancer Genome Atlas 373
- Cancer Genetic Markers of Susceptibility Project 373
- Support for future research in molecular diagnosis of cancer 374
- Role of the International Cancer Genome Consortium 374
- Future prospects of molecular diagnosis of cancer 375
- Companies involved in molecular diagnosis of cancer 375
8. Molecular Diagnostics in Biopharmaceutical Industry & Healthcare 381
- Introduction 381
- Molecular diagnostics in biopharmaceutical industry 381
- Molecular diagnostic technologies and drug discovery 381
- Molecular diagnostics and pharmacogenetics 382
- Molecular toxicology 383
- Gene expression studies 384
- Toxicogenomics 384
- Toxicoproteomics 385
- Mitochondrial assays 386
- MetaChip 386
- Molecular diagnostics and pharmacogenomics 387
- Applications molecular diagnostics in gene therapy 388
- Use of PCR to study biodistribution of gene therapy vectors 388
- PCR for verification of the transcription of DNA 389
- In situ PCR for direct quantification of gene transfer into cells 389
- Detection of retroviruses by reverse transcriptase (RT)-PCR 389
- Assessment of safety issues of gene transfer 389
- Quantitative PCR for monitoring the effectiveness of gene therapy 389
- Use of FISH for analysis of adeno-associated viral vector integration 389
- Monitoring of gene expression by green fluorescent protein 390
- Detection of microbial contamination in biopharmaceutical manufacturing
390
- Role of PCR in detecting contamination of biopharmaceuticals 390
- Contamination of biopharmaceuticals with prions 391
- DNA tagging for control and tracing of drug distribution channels 391
- Molecular diagnostics for organ transplantation 391
- Tissue typing 391
- Commercial products for transplant molecular diagnostics 393
- Post-cardiac transplant patient monitoring for rejection 395
- Blood Transfusion Screening 395
- Molecular tests for screening of blood supply for viruses 396
- Commercial molecular diagnostic technologies for blood screening 397
- Bridge Amplification Technology 398
- COBAS AmpliScreen HCV and HIV Assays 398
- INACTINE 398
- NucliSens Extractor system 398
- Pall' s enhanced Bacteria Detection System 399
- PCR combined with algorithm method 399
- Prions detection in human blood 400
- PRISMR automated system 400
- Procleix HIV-1/HCV Assay 400
- West Nile virus detection in human blood 401
- Limitations of molecular diagnostics for blood screening 401
- Molecular epidemiology 402
- Molecular epidemiology of genetic diseases 402
- Monogenic versus polygenic disorders 403
- Critical issues facing genetic epidemiology 403
- Molecular epidemiology of infectious diseases 403
- Methods and purposes 403
- Emerging infections 404
- Human vs. non-human infections 404
- Genetics and susceptibility to infectious disease 405
- Molecular epidemiology of cancer 405
- Molecular epidemiology of p53 gene mutations 406
- Molecular epidemiology of link between virus and cancer 406
- Molecular epidemiology and cancer prevention 406
- SNPs and molecular epidemiology 406
- Molecular diagnostics for identification of food-borne pathogens 406
- Introduction 406
- Molecular diagnostic methods used in food-borne infections 407
- Limitations of use of molecular probes in food analysis 408
- Optical biosensor for detection of Listeria-contaminated foods 408
- Companies with technologies for food pathogen detection 409
- Transmissible spongiform encephalopathies (TSEs) 410
- Molecular diagnosis of TSEs 410
- Companies involved in developing molecular diagnostics for TSEs 413
- Detection of genetically modified organisms in food 414
- Molecular diagnostics for detection of doping in sports 414
- Screening of synthetic glucocorticosteroids in human urine 415
- Detection of gene doping 415
- Role of molecular diagnostics in future healthcare 415
- Translation of genomic research into genetic testing for healthcare 416
- Molecular diagnostics and disease management 416
- Role of genetic biomarkers in disease management 417
- Role of molecular diagnostics in personalized medicine 417
- Integrated healthcare 417
- Screening 417
- Early diagnosis 418
- Prevention 418
- Therapy based on molecular diagnosis 418
- Monitoring of therapy 418
- Advantages and limitations of integrated healthcare 419
- Commercially available systems for integrated healthcare 419
- Combination of diagnostics and therapeutics 420
- Companies combining diagnostics and therapeutics 420
- Point-of-care diagnosis 421
- Technologies for point-of-care diagnosis 422
- Biochips for point-of-care diagnosis 423
- Companies developing point-of-care diagnosis 424
- Advantages versus disadvantages of point-of-care diagnosis 425
- The impact of molecular diagnostics on clinical laboratory practice 426
9. Molecular Diagnostics in Forensic Medicine and Biological Warfare 427
- Application of molecular diagnostics in forensic medicine 427
- Technologies 427
- Extraction of DNA from forensic samples 427
- Mitochondrial DNA (mtDNA) analysis 428
- Polymorphic Alu insertions 428
- Single Nucleotide Polymorphisms (SNP) analysis 429
- Short tandem repeat (STR) 429
- Fluorescent detection systems 430
- ABO genotyping 430
- DNA analysis for identification of ancient or historical specimens 430
- Applications 430
- Applications in criminology 431
- Identification of remains of military personnel 432
- Identification of remains of victims of mass disasters 432
- Parentage testing 433
- Gender determination 434
- Companies developing molecular diagnostics for forensic science 435
- Molecular detection of biological warfare agents 436
- Introduction to biological warfare agents 436
- Role of PCR in the diagnosis of biological warfare agents 437
- Multiplex PCR microarray assay to detect bioterror pathogens in blood 437
- Laboratory diagnosis of Anthrax 438
- Challenges in diagnosis of biological warfare agents 438
- US government efforts for detection of biological warfare agents 439
- The US Army Medical Research Institute of Infectious Diseases 439
- Homeland Security Advance Research Projects Agency 440
- Commercial development of diagnostic devices for biological agents 440
- Companies developing diagnostic devices for biological agents 440
- Biodefence microarray 443
- Identification of genetic markers of individual pathogens 443
- Microbial Identification System based on OptiChip"! 444
- Hand-Held Advanced Nucleic Acid Analyzer 444
- Nanogen' s portable detection device 444
- Nanode Array Sensor Microchips 445
- MicroChemLab 445
- BioThreat Alert Test Strip 445
- Benchtop living cell biosensor 446
- BioForce NanoArray sensor technology 446
- QTL handheld biosensor 446
- Analyte 2000 biosensor 447
- Airborne bacterial spore detection technology 447
- Destruction and detection of anthrax by lysin 447
- Biosensor based on mass spectrometry of microorganisms' s RNA 447
- Bead ARray Counter 448
- ProteinChip-based detection of bioterroism agents 448
- TIGER biosensor 448
- The PathAlert™ Detection System 449
- VereThreat"! 449
- Concluding remarks about biodefense applications of diagnostics 449
10. References 451
Tables
- Table 1 1: Landmarks in development of molecular technology and its
application to diagnosis 23
- Table 1 2: Applications of molecular diagnostics 42
- Table 2 1: Companies with products for nucleic acid isolation 51
- Table 2 2: Some commercially available real-time PCR systems 54
- Table 2 3: Applications of real-time PCR 55
- Table 2 4: A selection of companies with commercially available FISH
diagnostics 80
- Table 2 5: Selected companies with RNA diagnostic tests 81
- Table 2 6: Companies involved in whole genome amplification 89
- Table 2 7: Companies involved in sequencing 92
- Table 2 8: Comparison of methods of identification of unknown DNA
sequences 94
- Table 2 9: Classification of methods of gene expression analysis 95
- Table 2 10: A selection of companies with gene expression technologies 100
- Table 2 11: Companies involved in developing PNA diagnostics 103
- Table 3 1: Applications of biochip technology in relation to molecular
diagnostics 109
- Table 3 2: Companies developing whole genome chips/microarrays 115
- Table 3 3: Companies involved in biochips for molecular diagnostics 116
- Table 3 4: Companies developing microfluidic technologies 120
- Table 3 5: Biosensor technologies with potential applications in molecular
diagnostics 121
- Table 3 6: Important applications of biosensors 131
- Table 3 7: Companies involved in application of biosensors in molecular
diagnostics 131
- Table 3 8: Selected labels for nucleic acid detection 133
- Table 3 9: Selected companies with fluorescence and chemiluminescence
products 134
- Table 3 10: Companies involved in molecular beacon manufacture and
research 136
- Table 3 11: Selected companies involved in molecular imaging 143
- Table 3 12: Nanotechnologies with potential applications in molecular
diagnostics 144
- Table 3 13: Companies developing nanomolecular diagnostics 152
- Table 4 1: Applications of protein biochips/microarrays 163
- Table 4 2: Companies involved in developing diagnostic applications of
protein biochips 170
- Table 4 3: Disease-specific proteins in the cerebrospinal fluid of
patients 172
- Table 5 1: Mutation detection technologies 181
- Table 5 2: Technologies for SNP analysis 188
- Table 5 3: A sampling of companies involved in technologies for SNP
genotyping 198
- Table 5 4: Application of preimplantation genetic diagnosis in monogenic
disorders 207
- Table 5 5: Companies involved in prenatal/preimplantation diagnostics 209
- Table 5 6: CFTR genotyping in cystic fibrosis - companies and technologies
210
- Table 5 7: X-linked immunodeficiency disorders 214
- Table 5 8: Genes that cause cardiovascular diseases 220
- Table 5 9: Available molecular diagnostics for neurogenetic diseases 228
- Table 5 10: Companies offering genetic screening tests directly to
consumers 235
- Table 6 1: Molecular techniques for the diagnosis of infections 237
- Table 6 2: Bacteria and fungi that can be detected by recombinant DNA
tests 250
- Table 6 3: Viruses that can be detected by recombinant DNA methods 261
- Table 6 4: Companies with molecular diagnostics for avian influenza virus
H5N1 283
- Table 6 5: Companies developing POC tests for the diagnosis of infections
298
- Table 6 6: Selected companies involved in molecular diagnosis of
infections 301
- Table 7 1: Estimated new cases of cancer in the US at most involved organs
- 2008 303
- Table 7 2: Tumor suppressor genes, their chromosomal location, function,
and associated tumors 304
- Table 7 3: Viruses linked to human cancer 306
- Table 7 4: A classification of molecular diagnostic methods in cancer 308
- Table 7 5: Desirable characteristics of biomarkers for cancer 311
- Table 7 6: Approved monoclonal antibodies for cancer diagnosis 320
- Table 7 7: Methods for comparison of gene-expression profilling in tumor
specimens 322
- Table 7 8: Impact of in vivo molecular imaging of cancer on oncology
practice 334
- Table 7 9: Companies developing cancer molecular diagnostics 375
- Table 8 1: Applications of molecular diagnostics in the biopharmaceutical
industry 381
- Table 8 2: Molecular diagnostic technologies for drug discovery 382
- Table 8 3: Molecular diagnostic technologies used for pharmacogenetic
studies 382
- Table 8 4: Companies with novel molecular toxicology technologies 383
- Table 8 5: Applications of molecular diagnostics in gene therapy 388
- Table 8 6: Companies involved in transplant molecular diagnostics 393
- Table 8 7: Companies involved in molecular diagnostics of blood
transfusions 397
- Table 8 8: Pathogenic bacteria in food and targets for molecular
diagnostic probes 407
- Table 8 9: Companies involved in molecular diagnostics for food-borne
infections 409
- Table 8 10: Testing for harmful prions in brain tissue from dead cattle
410
- Table 8 11: Companies involved in developing molecular diagnostics for
TSEs 413
- Table 8 12: Companies combining molecular diagnostics and therapeutics 420
- Table 8 13: Applications of point-of-care diagnosis 421
- Table 8 14: Companies developing point-of-care diagnostic tests 424
- Table 9 1: Forensic and legal applications of molecular diagnostics. 430
- Table 9 2: Molecular technologies used for forensic applications 435
- Table 9 3: Classification of biological and chemical agents used as
weapons of mass destruction 436
- Table 9 4: Biological warfare agents that can be identified by PCR methods
437
- Table 9 5: Companies developing detection devices for biological warfare
agents 441
Figures
- Figure 1 1: Relation of molecular diagnostics to other technologies 43
- Figure 2 1: Rolling circle amplification technology 63
- Figure 2 2: A schematic view of the Invader operating system 71
- Figure 2 3: Principle of fluorescent in situ hybridization 75
- Figure 2 4: Repli-G system of Qiagen 90
- Figure 2 5: DNA sequencing process 91
- Figure 2 6: Electrochemical detection of DNA 105
- Figure 2 7: Elements of a Scorpions primer 106
- Figure 3 1: Affymetrix GeneChip technology 110
- Figure 3 2: Basic principle of a biosensor 121
- Figure 3 3: Surface plasmon resonance (SPR) technology 126
- Figure 6 1: Use of DNA chips in diagnosing microbial infections 239
- Figure 6 2: High throughput DNA pyrosequencing for pathogen discovery 242
Part II: Markets & Companies
11. Ethics, Patents and Regulatory issues 11
- Introduction 11
- Ethical concerns about genetic diagnosis 11
- Ethical guidelines for molecular diagnostics 12
- Ethical and regulatory aspects of direct-to-consumer genetic services 13
- Genetic testing for susceptibility to adult-onset cancer 15
- Ethics of preimplantation genetic diagnosis 15
- Preimplantation genetic diagnosis to screen for hereditary diseases 15
- PGD to test for susceptibiliy to cancer 16
- PGD and stem cells 16
- Genetic research on stored tissues 17
- Informed consent in clinical trials of in vitro devices 17
- Concluding remarks about ethical issues 17
- Insurance underwriting and gene tests 18
- Should genetic information be available to health insurers? 18
- A need for the re-examination of current views 19
- Genetic Information Nondiscrimination Act of US 19
- Patents for molecular diagnostics 19
- PCR patents 19
- Patenting DNA sequences 20
- US policy on gene patenting relevant to molecular diagnostics 20
- The impact of disease gene patents on molecular diagnostics 21
- Licensing problems associated with genetic testing 21
- Role of the WHO in genetic testing standards 21
- Regulatory issues in the US 22
- Assay Migration Studies for In Vitro Diagnostic Devices 22
- Assessment of diagnostic accuracy 22
- Sensitivity and specificity 22
- Documentation of diagnostic accuracy 23
- Assessment of laboratory-developed tests used by Medicare recipients 24
- Discovery of incidental findings on genetic screening 25
- Evaluation of companion diagnostics/therapeutic for cancer 25
- FDA regulation of multivariate index assays 25
- FDA guidance for IVDs to detect pathogens 27
- FDA guidelines for devices to detect and differentiate HPV 27
- FDA' s Microarray Quality Control 28
- FDA and point-of-care diagnosis 28
- Genetic testing of rare disorders 29
- Quality control of molecular diagnostic laboratory procedures 29
- Quality control of point-of-care tests 30
- Regulation of IVD by the FDA 30
- Regulation of in vivo diagnostics by the FDA 31
- Regulation of analytic-specific reagents 32
- Regulatory aspects of FISH 32
- Regulation of genetic testing 32
- Role of the FDA in genetic testing 32
- Regulatory issues concerning blood and plasma products 33
- United States Diagnostics Standards 33
- Regulation of in vitro diagnostics in the EU 34
- EU regulations for testing of blood products 34
- Regulation of genetic testing in EU 34
- Evaluation of diagnostic laboratory tests in the UK 35
- Pre-implantation genetic diagnosis in the UK 35
12. Markets for Molecular Diagnostics 37
- Introduction 37
- Methods for study of molecular diagnostic markets 37
- The overall market for diagnostic technologies 38
- Molecular diagnostic markets according to technologies 38
- Marketing strategies according to technologies 39
- Nucleic acid isolation market 39
- Market for PCR-based tests 39
- DNA sequencing market 39
- Cytogenetic market 40
- Market for FISH technologies 40
- Biochip/microarray market 40
- Biosensor market 41
- Nanobiotechnology for molecular diagnostics 41
- Markets for gene expression technologies 41
- Reagents and other disposable laboratory materials 41
- Market for immunochemistry diagnostic 42
- Markets for tissue diagnostics 42
- Molecular diagnostic markets according to therapeutic areas 42
- Genetic disorders 43
- Prenatal testing 44
- Cancer 44
- Potential markets for cancer diagnosis according to type of cancer 45
- Infectious diseases 45
- Sexually transmitted diseases 46
- Hospital-acquired infections 47
- Testing for HIV drug resistance 48
- Potential markets for avian influenza diagnostics 48
- Cardiovascular diseases 48
- Neurological disorders 49
- Food testing 49
- Screening of blood for transfusion 49
- Tissue typing for transplantation 49
- Marketing opportunities according to geographic areas 49
- Unmet needs in molecular diagnostics 50
- Major market trends 51
- Markets according to home-brew and FDA-approved tests 51
- Decentralization of molecular diagnostics 52
- Point-of-care testing 52
- Development of personalized medicine 53
- Cost of sequencing the human genome 53
- Cost of genotyping 53
- Development of low-cost tests 54
- Simplification of test procedures 54
- Increasing role of proteomics in clinical diagnostics 55
- Forensic and legal applications 55
- Marketing strategies 55
- Role of alliances in commercialization of molecular diagnostics 56
- Acquisitions vs collaborations 56
- Analysis of collaborations in molecular diagnostics 59
- Licensing of the technologies 59
- Strategies related to laboratory facilities and technologies 60
- Strategies relevant to the healthcare system 60
- Cost-Benefit studies 60
- Genetic susceptibility testing 60
- Preventive medicine strategies 61
- Targeting treatable and common diseases 61
- Information/education 61
- Physician education 61
- Patient education 62
- European diagnostic information platform 63
- Regulatory strategies 63
- Merger of in vitro and in vivo diagnostics 63
- Integration of diagnostics with therapeutics 63
- Diagnostic applications in clinical trials 64
- Prospects for development of new technologies 64
- Drivers for the development of molecular diagnostics 64
- Factors slowing the development of molecular diagnostics 64
- Government support of research relevant to molecular diagnostics 65
- Cost of sequencing the human genome 65
- European projects for improving molecular diagnostics 67
- European Consortium for developing new DNA analysis tools 67
- EU project for improvement of IVD tools procedures 68
- Genetic knowledge parks in the UK 68
- Molecular diagnostic opportunities in defense against bioterrorism 68
- Molecular diagnostics for food safety 69
- POC diagnostics for the developing countries 69
13. Companies involved in molecular diagnostics 71
- Introduction 71
- Major players in molecular diagnostics 71
- Profiles of selected companies 72
- Collaborations 417
Tables
- Table 12 1: Share of in vitro diagnostics in the global diagnostic market
2008-2018 38
- Table 12 2: Molecular diagnostics markets according to technologies from
2008-2018 38
- Table 12 3: Molecular diagnostics markets according to applications
2008-2018 42
- Table 12 4: Markets in 2008 for tests to screen healthy persons for
genetic disorders 43
- Table 12 5: Markets in 2008 for molecular diagnostic tests for cancer 44
- Table 12 6: Molecular diagnostic markets for selected cancers 2008-2018 45
- Table 12 7: Markets value in 2008 for molecular diagnostic screening for
infections 46
- Table 12 8: Future markets for HAI diagnostics 2008-2013 47
- Table 12 9: Molecular diagnostic markets according to geographical areas
2008-2018 50
- Table 12 10: Molecular diagnostic markets according to home-brew and
approved tests 51
- Table 12 11: Marketing strategies for molecular diagnostics 55
- Table 12 12: Takeovers of molecular diagnostic companies 56
- Table 12 13: Advantages of the integration of diagnostics with
therapeutics 63
- Table 13 1: Top ten players in molecular diagnostics 71
- Table 13 2: Collaborations of companies in molecular diagnostics 417
Figures
- Figure 12 1: Unmet needs in applications of molecular diagnostics 51
- Figure 12 2: Proportion of various areas in molecular diagnostic
collaborations 59
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