Sequencing
Table 2: Genome screening projects Project
AstraZeneca 2M Genomes Project
Ancestry.com 23andMe
Million Veteran Program Precision Medicine Initiative Korea Biobank Project
European Network for Genetic and Genomic Epidemiology (ENGAGE) Resilience Project
China Kadoorie Biobank Repository
Kaiser Permanente: Genes, Environment, and Health (RPGEH) Repository, UK Biobank Repository, Consortium deCode Genetics
Regneron/Kaiser Permanente MyCode® Community Health Initiative Repository French Genome Project
Vanderbilt's BioVU Repository BioBank Japan Repository Specimens
Leiden Open Variation Database (LOVD) Repository Psychiatric Genomics Consortium (PGC) 100K Wellness Project Turkish Genome Project Genomics England
Actionable Cancer Genome Initiative (ACGI) Data-Sharing Project Genome Asia 100K Consortium Saudi Human Genome Program East London Genes & Health
Exome Aggregation Consortium (ExAC) Electronic Medical Records and Genomics (eMERGE) Network Repository
Estonian Genome Project, Estonian Biobank and the Estonian Genome Center (EGCUT) International Multiple Sclerosis Genetics (IMSG) International Genomics of Alzheimer's Project (IGAP)
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Cancer Moonshot 2020 Consortium Phase 1 DECIPHER Repository
GENIE/AACR Data-Sharing Project
International Cancer Genome Consortium (ICGC) CIMBA Consortium
Tohoku Medical Megabank Project (ToMMO) Sequencing Initiative Suomi (SISu) Genome Korea in Ulsan UK10K Research Project T2D-GENES Consortium PopGen (Germany) SardiNIA Study Qatar Genome
Personal Genome Project
Clinical Sequencing Exploratory Research (CSER) Consortium Scottish Genomes Partnership (SGP) TBResist
Faroe Genome Project (FarGen)
(Target) Cohort size*
2,000,000 1,400,000 1,000,000 1,000,000 1,000,000 618,958 600,000 589,306 512,000 500,000 500,000 500,000 250,000 235,000 215,000 200,000 170,000 170,000 100,000 100,000 100,000 100,000 100,000 100,000 100,000 60,706 55,028 52,000 50,000 40,000 20,000 20,000 19,014 17,000 16,000 15,000 15,000 10,000 10,000 10,000 10,000 10,000 7,000 6,500 5,015 4,000 3,000 2,600 1,500
African Genome Variation Project 1,481 Human Genome Diversity Project Genome of the Netherlands (GoNL) Singapore Genome Variation Program GenomeDenmark
1,050 750 268 150
* these figures are for samples and are taken from published information on the projects
regions may require data derived from their citizens to reside within the country or region. For those organisations that utilise external lab- oratories to perform the sequencing itself, another option is to rely on the laboratory to also provide the necessary storage and computational services, such as Illumina BaseSpace or BGI Online. There are many laboratories that provide NGS services in a CLIA-certified environment.
Clinical diagnostic laboratories work directly with hospitals and physicians to provide diagnosis and treatment options for individual patients. They may use NGS technologies, but deliver clinical reports and advice rather than just a set of variants.
Companion and complementary diagnostics
Perhaps the most visible applications of NGS in the clinical realm are companion and complementary diagnostics. A ‘companion diagnostic’ is a medical device, often an in vitro device, which provides information that is essential for the safe and effec- tive use of a corresponding drug or biological product. A ‘complementary diagnostic’ is a device which is essential for the safe and effective use of a corresponding medicinal product to identify, before and/or during treatment:
l Patients who are most likely to benefit from the corresponding medicinal product, or l patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product.
The oncology therapy area is especially active in its use of NGS technologies, which are well-suited to characterising tumours based on their genomic variants, often mutations specific to the individual tumour. One of the first examples of a drug with an associated companion diagnostic (though not NGS-based) is trastuzumab (HERCEPTIN®, 1998). A more recent example is the Foundation- One™ from Foundation Medicine, Inc, which interrogates 324 genes in tumour tissue for a vari- ety of variant types and total mutational burden in order to select the most appropriate therapy for the individual across a range of cancer types. There are a sizeable number of large-scale biobanking and genomic sequencing initiatives cur- rently under way, as shown in Table 2. An out- standing question is how can the industry make use of these data for both discovery and diagnostic development purposes? For example, can it use sequence information to stratify biobank subjects for enrolment in clinical trials? For this to happen,
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