Celera Genomics Completes the First Assembly of the Human Genome; Assembled Genome Has 3.12 Billion Base Pairs
ROCKVILLE, MD.--(BW HealthWire)--June 26, 2000--Celera Genomics (NYSE: CRA), a PE Corporation business, today announced that it has completed the first assembly of the human genome, which has revealed a total of 3.12 billion base pairs in the human genome. An assembled genome is one where the location and order of the letters of genetic code along the chromosomes are known. Celera now begins the analysis and annotation phase.
Celera uses two independent approaches to assemble the human genome. First, Celera's Whole Genome Shotgun Assembly utilizes all of the Celera generated sequence data from the DNA of five individuals. Celera assembled the human genome using 26.4 million sequences of 550 base pairs long for a total of 14.5 billion base pairs sequenced, or 4.6X sequence coverage. At 4.6X more than 99 percent of the genome is covered. Celera's whole genome shotgun sequencing technique involves sequencing from both ends of the double strands of DNA sequence. Celera's use of these paired end sequences is a key tool for assembling the genome.
Celera's paired end-sequencing strategy has now produced paired sequence reads that cover the human genome 35.6 times or 35.6X of paired sequence and clone coverage. This unprecedented genome coverage was achieved using a new system for isolating fragments of DNA for sequencing developed by Celera scientists Hamilton Smith and Robert Holt. This new system enables Celera to obtain particularly long segments for sequencing derived from stretches of DNA 50,000 letters long. These long segments provided almost 50 percent of the paired sequence coverage and aided greatly in producing long stretches of accurately ordered DNA. In addition, Celera included data from GenBank, the public database, produced primarily by the public genome effort. In order to eliminate any bias to the assembly associated with the incomplete map and assembly information from the GenBank data, Celera shredded the data into 13.6 million segments 550 base pairs long for a total of 7.48 billion base pairs. These data produced additional redundancy.
The calculation to perform the assembly involved 500 million trillion base to base comparisons requiring over 20,000 CPU (central processor unit) hours on Celera's supercomputer. This believed to be the largest computational biology calculation to date.
The second assembly method used by Celera is its "Regional Assembler." This is being used to cross validate the results from the whole genome shotgun assembly. Celera used the bacteria artificial chromosome (BAC) data from GenBank sorted into regions along the chromosomes. Celera data was placed to the identified regions followed by the assembly into proper order utilizing Celera's shotgun assembler. The results of this assembly process are sequence segments known as "scaffolds" reconstituting the 24 human chromosomes. Most of the genome is covered by sequence scaffolds of one million base pairs or larger.
"To say that the completion of this first assembly of the human genome is an exciting milestone for Celera and its scientific staff, is an understatement. We have assembled 3.12 billion letters of genetic code and know for the first time in history the order and orientation of this information," said J. Craig Venter, Ph.D., Celera's president and chief scientific officer. "I also want to congratulate our colleagues associated with the public genome effort on their working draft sequence. Celera will now move to the next phase of annotation whereby these located genes are studied to better understand their function. Celera subscribers will now be able to compare genetic data from the fruit fly, human and mouse in order to make discoveries that could lead to improved treatments and possible cures for disease."
"Our announcement today of the first assembly of the human genome and that of a working draft by the publicly funded human genome project are significant achievements in science," said Tony White, PE Corporation's chairman, president and chief executive officer. "We are also proud of the contributions that PE Biosystems, Celera's sister business, has made to these accomplishments by providing the sequencing instruments, which were so essential for both Celera's sequence and the public working draft."
Whole Genome Sequencing
Celera began to sequence the human genome on September 8, 1999, using the whole genome shotgun technique that its scientists pioneered in sequencing the first complete genome in 1995 at The Institute for Genomic Research (TIGR). This technique involves randomly shearing the human chromosomes into millions of pieces of 2,000 and 10,000 base pairs in length. The chromosome fragments are inserted into a plasmid vector and propagated in E. coli to produce millions of copies of each fragment. Celera scientists then sequence both ends of each fragment. The millions of sequences representing billions of letters of genetic code are then assembled into the proper order using proprietary genome assembly algorithms and the powerful Celera supercomputing facility. This results in the reconstruction of the linear sequence of the 23 pairs of human chromosomes.
The human genome sequencing effort funded by governments and the Wellcome Trust is based on sequencing large segments of human DNA in bacterial artificial chromosomes (BAC) using a variation of the shotgun sequencing method. With this approach, approximately 30,000 BAC clones have to be sequenced and their order mapped to reassemble the 23 human chromosomes. There are on average 150,000 letters of human DNA in a BAC. Its "draft" sequence represents most of these base pairs; however the fragments of DNA sequence are largely unordered. By combining the Celera whole genome data with the individual clone "draft" BAC data, Celera orders the sequence within each BAC segment and then places them in the proper order to construct the genome's sequence. Celera has simultaneously and independently assembled the genome with its whole genome assembly algorithms. The combination of these two complementary genome sequencing and assembly approaches has greatly reduced the time necessary for Celera to finish the sequence and assembly of the human genome.
Celera's Donor Pool
Celera follows a strict Institutional Review Board (IRB) protocol, which allows for a pool of up to 30 individuals to be recruited for the human genome sequencing effort. Recruitment was done via self-referral, newspaper ads, and outreach activities to ensure ethnic diversity. Five individuals have been chosen from Celera's donor pool. These donors are men and women from a variety of self-disclosed ethnic backgrounds.
Celera's Technology
Celera has rapidly sequenced and assembled the fruit fly genome and the human genome, and has nearly completed half the sequencing of the mouse genome. The speed with which Celera is capable of doing this is directly attributable to the state-of-the art technology employed in various stages of the sequencing process. Celera has 300 ABI PRISM(R) 3700 automated sequencers in its high-throughput DNA sequencing factory. These machines, made by PE Biosystems and developed by the PE Biosystems' team led by its president Michael Hunkapiller, Ph.D., have enabled researchers worldwide to use this process on an industrial scale for the first time. Prior to its production in 1999, researchers spent months, if not years, sequencing portions of the genome.
Another key to Celera's success in genomic sequencing has been the development of high performance supercomputing technology. Celera's computing partner is Compaq Computer Corporation. In completing the sequencing and assembly of the 3.12 billion letters of genetic code, Celera relied exclusively on networked Compaq AlphServer computers running Tru64 UNIX and TruCluster software to manage the more than 80 terabytes of data and to perform what are believed to be some of the most complex computations in the history of supercomputing. Celera's final assembly computations were run on Compaq's new AlphaServer GS160 because the algorithms and data required 64 gigabytes of shared memory to run successfully. Celera also has an alliance with Oracle for complete database development and infrastructure for all planned Celera Genomics databases, including Drosophila (fruit fly), human, mouse, rice and Arabidopsis (mustard weed).
Celera Milestones
While assembly of the human genome represents the achievement of one of Celera's most significant scientific goals, Celera management has consistently explained that it represents more of a starting line than a finish line in the genomics revolution. Several areas continue to fuel activity at Celera, and these efforts feed Celera's business model. These areas include the following:
-- Human Genome
On January 10, 2000, Celera announced it had compiled data
covering 90% of the human genome. On April 6, 2000, Celera
announced it had completed the sequencing phase of the genome from
one human being. With today's announcement, Celera has completed
the assembly phase of the genome. Celera now begins the phase
known as annotation whereby the located genes are further analyzed
to start the process of understanding their particular function.
Celera is on target to submit a paper for publication on the
consensus genome later this year. Upon publication, the data will
be freely available to academic researchers worldwide via Celera's
web site. Celera's academic, pharmaceutical, and biotechnology
subscribers have immediate access to the database and
sophisticated bioinformatics tools for analysis of the genome.
Other database companies will not be able to redistribute Celera's
data.
-- Mouse Genome
Celera announced on June 1, 2000 that it has sequenced
approximately 1.15 billion base pairs of mouse DNA. Celera began
to sequence the mouse on April 6, 2000. This project is of
critical importance to biomedical researchers using the mouse as a
model organism for studies of human biology and medicine. Having
access to the mouse genome should allow researchers to make
important discoveries in the regulation of human genes based on
common structure and mechanisms shared with mouse genes. Celera is
now on target to complete the sequencing of the mouse by the end
of 2000. Celera anticipates sequencing other species to aid with
comparative genomics.
With continued development and expansion of Celera's unique databases, sales of subscriptions to commercial and academic users will be a priority. Celera also will continue to pursue avenues, both directly and by partnering with others, to generate value through discovery efforts based on extending sequencing data to biological and medical breakthroughs.
PE Corporation comprises two operating groups. The PE Biosystems Group (NYSE: PEB), with sales of $1.2 billion during fiscal 1999, develops and markets instrument-based systems, reagents, software and contract services to the life science industry and research community. The Celera Genomics Group (NYSE: CRA), headquartered in Rockville, MD, intends to become the definitive source of genomic and related medical information. PE Biosystems is headquartered in Foster City, CA, and comprises four divisions: Applied Biosystems, PE Informatics, PerSeptive Biosystems, and Tropix. Information about the company, including reports and other information filed by the company with the Securities and Exchange Commission, is available on the worldwide web at www.pecorporation.com or by phoning 800.762.6923.
Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," "expect," "anticipate," "should," "intend," "planned," "estimated," and "potential," among others. These forward-looking statements are based on PE Corporation's current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, PE Corporation notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. The risks and uncertainties that may affect the operations, performance, development, and results of Celera Genomics' businesses include but are not limited to (1) operating losses to date; (2) a unique and developing business plan; (3) dependence on the timely completion of the sequencing and assembly of the human genome; (4) uncertainty of revenue growth; (5) unproven use of genomics information to develop products; (6) intense competition in the evolving genomics industry; (7) dependence on customers in and subject to the risks of the pharmaceutical and biotechnology industries; (8) heavy reliance on strategic relationship with the PE Biosystems group; (9) potential product liability claims; (10) liabilities related to use of hazardous materials; (11) lengthy sales cycle; (12) dependence on the unique expertise of its scientific and management staff; (13) uncertainty of patent, copyright and intellectual property protection; (14) dependence on computer hardware, software, and internet applications; (15) access to biological materials; (16) legal, ethical and social issues affecting demand for products; (17) disruptions caused by rapid growth of the business; (18) government regulation of its products and services; (19) risks of future acquisitions; and (20) other factors that might be described from time to time in PE Corporation's filings with the Securities and Exchange Commission.
Celera, Celera Genomics, and PE Biosystems are trademarks of PE Corporation.
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