The $1,000 genome refers to an era of predictive and personalized medicine during which the cost of fully sequencing an individual's genome (WGS) is roughly one thousand USD. [1] [2] It is also the title of a book by British science writer and founding editor of Nature Genetics, Kevin Davies. [3] By late 2015, the cost to generate a high-quality "draft" whole human genome sequence was just below $1,500. [4]
The "$1,000 genome" catchphrase was first publicly recorded in December 2001 at a scientific retreat to discuss the future of biomedical research following publication of the first draft of the Human Genome Project (HGP), convened by the National Human Genome Research Institute at Airlie House in Virginia. [5] The phrase neatly highlighted the chasm between the actual cost of the Human Genome Project, estimated at $2.7 billion over a decade, and the benchmark for routine, affordable personal genome sequencing.
On 2 October 2002, Craig Venter introduced the opening session of GSAC (The Genome Sequencing and Analysis Conference) at the Hynes Convention Center in Boston: "The Future of Sequencing: Advancing Towards the $1,000 Genome." Speakers included George M. Church and executives from 454 Life Sciences, Solexa, U.S. Genomics, VisiGen and Amersham plc. [6] [7] In 2003, Venter announced that his foundation would earmark $500,000 for a breakthrough leading to the $1,000 genome. [8] That sum was subsequently rolled into the Archon X Prize.
In October 2004, NHGRI introduced the first in a series of '$1,000 Genome' grants designed to advance "the development of breakthrough technologies that will enable a human-sized genome to be sequenced for $1,000 or less." [9]
In a January 2006 article in Scientific American making the case for the Personal Genome Project, George M. Church wrote
The "$1,000 genome" has become shorthand for the promise of DNA-sequencing capability made so affordable that individuals might think the once-in-a-lifetime expenditure to have a full personal genome sequence read to a disk for doctors to reference is worthwhile. [10]
In 2007, the journal Nature Genetics invited dozens of scientists to respond to its 'Question of the Year':
The sequencing of the equivalent of an entire human genome for $1,000 has been announced as a goal for the genetics community... What would you do if [the $1,000 genome was] available immediately? [11]
In May 2007, during a ceremony held at Baylor College of Medicine, 454 Life Sciences founder Jonathan Rothberg presented James D. Watson with a digital copy of his personal genome sequence on a portable hard drive. Rothberg estimated the cost of the sequence—the first personal genome produced using a next-generation sequencing platform—at $1 million. [12] Watson's genome sequence was published in 2008. [13]
A number of scientists have highlighted the cost of additional analysis after performing sequencing. Bruce Korf, past president of the American College of Medical Genetics, described "the $1-million interpretation." [14] [ failed verification ] Washington University's Elaine Mardis prefers "the $100,000 analysis." [15]
At the end of 2007, the biotech company Knome debuted the first direct-to-consumer genome sequencing service at an initial price of $350,000 (including analysis). One of the first clients was Dan Stoicescu, a Swiss-based biotech entrepreneur. [16] As the costs of sequencing continued to plummet, in 2008, Illumina announced that it had sequenced an individual genome for $100,000 in reagent costs. Applied Biosystems countered by saying the cost on its platform was $60,000. [17] Pacific Biosciences became the latest entrant in what The New York Times called "a heated race for the '$1,000 genome'". [18] [19] In 2009, Stanford University professor Stephen Quake published a paper sequencing his own genome on an instrument built by Helicos Biosciences (a company he co-founded) for a reported cost in consumables of $48,000. [20] That same year, Complete Genomics debuted its proprietary whole-genome sequencing service for researchers, charging as little as $5,000/genome for bulk orders. [21]
In 2010, Illumina introduced its individual genome sequencing service for consumers, who were required to present a doctor's note. The initial price was $50,000/person. One of the first clients was former Solexa CEO John West, who had his entire family of four sequenced. [22] In January 2012, Life Technologies unveiled a new sequencing instrument, the Ion Proton Sequencer, which it said would achieve the $1,000 genome in a day within 12 months. [23] Sharon Begley wrote: "After years of predictions that the '$1,000 genome' – a read-out of a person's complete genetic information for about the cost of a dental crown—was just around the corner, a U.S. company is announcing... that it has achieved that milestone." [24]
In January 2014, Illumina launched its HiSeq X Ten Sequencer, claiming to have produced the first $1,000 genome at 30× coverage. Some researchers hailed the HiSeq X Ten's release as a milestone – Michael Schatz of Cold Spring Harbor Laboratory said that "it is a major human accomplishment on par with the development of the telescope or the microprocessor". However, critics pointed out that the $10 million upfront investment required to purchase the system would deter customers. Furthermore, the $1,000 genome cost calculation left out overheads, such as the cost of powering the machine. [25] In September 2015, Veritas Genetics (co-founded by George Church) announced $1,000 full-genome sequencing including interpretation for participants in the Personal Genome Project. [26]
In April 2017, the newly formed European company Dante Labs started offering the WGS for $900. [27] [28] In 2017, Beijing Genomics Institute began offering WGS for $600. [29] In July 2018, on Amazon Prime Day, Dante Labs offered it for $349. [30] In November 2018, around the time of Black Friday, Dante Labs offered WGS for the first time less than $200, [31] and Veritas Genetics for two days for the same price of $199 offered WGS limited to a thousand customers. [32] In March of the same year, geneticist Matthew Hurles of Wellcome Sanger Institute noted that the private companies, including Illumina, [33] are currently competing to reach a new target for WGS of only $100. [34] On 18 February 2020, Nebula Genomics announced that has partnered up with BGI Group to start offering 30x WGS for $299. [35]
It was originally announced that the revamped Archon Genomics X PRIZE presented by Medco would hold a $10-million grand prize competition in January 2013 for the team that reaches (or comes closest to reaching) the $1,000 genome. The grand prize would go to "the team(s) able to sequence 100 human genomes within 30 days to an accuracy of 1 error per 1,000,000 bases, with 98% completeness, identification of insertions, deletions and rearrangements, and a complete haplotype, at an audited total cost of $1,000 per genome." [36] In August 2013, the Archon Genomics X PRIZE was cancelled, as the founders felt it had been "Outpaced by Innovation," and "was not incentivizing the technological changes". [37]
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk DNA.
Genomics is an interdisciplinary field of molecular biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dimensional structural configuration. In contrast to genetics, which refers to the study of individual genes and their roles in inheritance, genomics aims at the collective characterization and quantification of all of an organism's genes, their interrelations and influence on the organism. Genes may direct the production of proteins with the assistance of enzymes and messenger molecules. In turn, proteins make up body structures such as organs and tissues as well as control chemical reactions and carry signals between cells. Genomics also involves the sequencing and analysis of genomes through uses of high throughput DNA sequencing and bioinformatics to assemble and analyze the function and structure of entire genomes. Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.
A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine). This is then reported as a text string, called a read. Some DNA sequencers can be also considered optical instruments as they analyze light signals originating from fluorochromes attached to nucleotides.
Genome projects are scientific endeavours that ultimately aim to determine the complete genome sequence of an organism and to annotate protein-coding genes and other important genome-encoded features. The genome sequence of an organism includes the collective DNA sequences of each chromosome in the organism. For a bacterium containing a single chromosome, a genome project will aim to map the sequence of that chromosome. For the human species, whose genome includes 22 pairs of autosomes and 2 sex chromosomes, a complete genome sequence will involve 46 separate chromosome sequences.
BGI Group, formerly Beijing Genomics Institute, is a Chinese genomics company with headquarters in Yantian, Shenzhen. The company was originally formed in 1999 as a genetics research center to participate in the Human Genome Project. It also sequences the genomes of other animals, plants and microorganisms.
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery.
George McDonald Church is an American geneticist, molecular engineer, chemist, serial entrepreneur, and pioneer in personal genomics and synthetic biology. He is the Robert Winthrop Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard University and Massachusetts Institute of Technology, and a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
454 Life Sciences was a biotechnology company based in Branford, Connecticut that specialized in high-throughput DNA sequencing. It was acquired by Roche in 2007 and shut down by Roche in 2013 when its technology became noncompetitive, although production continued until mid-2016.
The Archon Genomics X PRIZE presented by Express Scripts for Genomics, the second X Prize offered by the X Prize Foundation, based in Playa Vista, California, was announced on October 4, 2006 stating that the prize of "$10 million will be awarded to the first team to rapidly, accurately and economically sequence 100 whole human genomes to an unprecedented level of accuracy." The 30 day evaluation phase of the competition to begin on September 5, 2013, was canceled August 22, 2013 and this cancellation was debated on March 27, 2014.
Personal genomics or consumer genetics is the branch of genomics concerned with the sequencing, analysis and interpretation of the genome of an individual. The genotyping stage employs different techniques, including single-nucleotide polymorphism (SNP) analysis chips, or partial or full genome sequencing. Once the genotypes are known, the individual's variations can be compared with the published literature to determine likelihood of trait expression, ancestry inference and disease risk.
Whole genome sequencing (WGS) is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria and, for plants, in the chloroplast.
Complete Genomics is a life sciences company that has developed and commercialized a DNA sequencing platform for human genome sequencing and analysis. This solution combines the company's proprietary human genome sequencing technology with its informatics and data management software to provide finished variant reports and assemblies at Complete Genomics’ commercial genome center in Mountain View, California.
Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).
Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome. It consists of two steps: the first step is to select only the subset of DNA that encodes proteins. These regions are known as exons—humans have about 180,000 exons, constituting about 1% of the human genome, or approximately 30 million base pairs. The second step is to sequence the exonic DNA using any high-throughput DNA sequencing technology.
Transmission electron microscopy DNA sequencing is a single-molecule sequencing technology that uses transmission electron microscopy techniques. The method was conceived and developed in the 1960s and 70s, but lost favor when the extent of damage to the sample was recognized.
In DNA sequencing, a read is an inferred sequence of base pairs corresponding to all or part of a single DNA fragment. A typical sequencing experiment involves fragmentation of the genome into millions of molecules, which are size-selected and ligated to adapters. The set of fragments is referred to as a sequencing library, which is sequenced to produce a set of reads.
Sir David Klenerman is a British biophysical chemist and a professor of biophysical chemistry at the Department of Chemistry at the University of Cambridge and a Fellow of Christ's College, Cambridge.
In genetics, coverage is one of several measures of the depth or completeness of DNA sequencing, and is more specifically expressed in any of the following terms:
A plant genome assembly represents the complete genomic sequence of a plant species, which is assembled into chromosomes and other organelles by using DNA fragments that are obtained from different types of sequencing technology.
Personalized genomics is the human genetics-derived study of analyzing and interpreting individualized genetic information by genome sequencing to identify genetic variations compared to the library of known sequences. International genetics communities have spared no effort from the past and have gradually cooperated to prosecute research projects to determine DNA sequences of the human genome using DNA sequencing techniques. The methods that are the most commonly used are whole exome sequencing and whole genome sequencing. Both approaches are used to identify genetic variations. Genome sequencing became more cost-effective over time, and made it applicable in the medical field, allowing scientists to understand which genes are attributed to specific diseases.