Pacific Biosciences

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Pacific Biosciences
Type Public company, NASDAQPACB
Founded 2004
Headquarters Menlo Park, CA 37°28′43″N 122°09′03″W / 37.4787°N 122.1507°W / 37.4787; -122.1507
Key people Michael Hunkapiller, Chairman, CEO, and President
Products biotechnology
Website www.pacificbiosciences.com

Pacific Biosciences is a biotechnology company founded in 2004[1] that develops and manufactures systems for gene sequencing and some novel real time biological observation.[2] They describe their platform as single molecule real time sequencing (SMRT), based on the properties of zero-mode waveguides. Their first commercial product, the PacBio RS, was sold to a limited set of customers in 2010[3] and was commercially released in early 2011.[4] A new version of the sequencer called the PacBio RS II was released in April 2013.[5][6] On 25 September 2013 a partnership between Pacific Biosciences and Roche Diagnostics was announced for the development of in vitro diagnostic products using the technology, with Roche providing $75 million in the deal.[7]

History[edit]

The company was founded based on research done at Cornell University, that combined semiconductor processing and photonics with biotechnology research.[1] It was initially founded under the name Nanofluidics, Inc. The company raised nearly $400 million in six rounds of primarily venture capital financing, making it one of the most capitalized startups in 2010 leading up to their public offering in October of that year.[8] Key investors included Mohr Davidow Ventures, Kleiner, Perkins, Caufield & Byers, Alloy Ventures, and Wellcome Trust.[1]

Recognitions[edit]

The company received the Technology Pioneer Award from the World Economic Forum in 2009.[1][9]

In 2010, The Scientist magazine named the company and their first product the top life science innovation of the year[10] and the company received the 2010 Advanced Sequencing Technology Award from the National Human Genome Research Institute.[11] Technology Review magazine included them in their list of the top 50 most innovative companies for both 2010 and 2011.[12][13] Founder and Chief Technical Officer Dr. Stephen Turner was awarded the 2010 Ewing Marion Kauffman Foundation Outstanding Postdoctoral Entrepreneur award for his work at the company.[14]

Going public[edit]

Pacific Biosciences first offered stock on NASDAQ under the symbol PACB. They sold 12,500,000 shares at an initial price of $16 per share and raised approximately $200 million in an initial public offering of stock on October 27, 2010.[15]

Products[edit]

The company’s first scientific instrument, called the “PacBio RS”, was released to a limited set of eleven customers in late 2010.[16] Sequencing provider GATC Biotech was selected by Pacific Biosciences as its first European service provider in late 2010.[17] The product was then commercially released in early 2011.[4] A new version of the sequencer called the "PacBio RS II" was released in April 2013; it produces longer sequence reads and offers higher throughput than the original instrument.[5][6]

A PacBio RSII sequencer

To use the instrument, customers must also purchase reagent packs for DNA preparation and sequencing and small plastic cells called “SMRT Cells”. Each cell is slightly less than one centimeter square and contains thousands of zero-mode waveguides. The cells are sold in packs of eight. Their secondary analysis bioinformatics product, called “SMRT Portal”, is open source.[18] In 2013, the company released new bioinformatics tools for automated genome assembly (HGAP) and finishing to 99.999% accuracy (Quiver).[19][20][21]

In May 2010, they published an article in Nature Methods, showing that their instrument can detect methylation of DNA strands without altering the DNA.[22] In 2012 scientists used SMRT sequencing to generate full bacterial methylomes.[23]

In April 2013, the company released a new version of its sequencer called the PacBio RS II with improved throughput[5][6] and then in October 2013 released updated chemistry with a mean read length of 8,500 bases (N50 of 10,000 bases) and longest reads exceeding 30,000 bases.[24] In October of 2014 the company released an updated chemistry with a mean read length of 10,000 to 15,000 bases and longest reads exceeding 40,000 bases.[25]

Key publications[edit]

Before the first commercial release of their sequencer, scientists published in January 2009 the first sequence data generated from a single molecule real time sequencing in the journal Science.[26] Then in April 2010, scientists published a paper in Nature showing that they had used zero-mode waveguides to perform real-time observation of ribosomal translation.[27]

Demonstrating the value for bacterial sequencing, scientists from Pacific Biosciences and other institutions published in January 2011 a paper in the New England Journal of Medicine demonstrating the origin of the 2010 cholera outbreak in Haiti.[28] In August 2011, Pacific Biosciences scientists and collaborators at other organizations published a paper in the New England Journal of Medicine describing the classification of the E. coli strain causing the virulent 2011 outbreak in Germany responsible for hundreds of cases of hemolytic–uremic syndrome.[29] This paper showed that the strain of E. coli responsible for the outbreak had acquired a Shiga-toxin–encoding phage through lateral gene transfer. In July 2012, several papers were published in peer-review journals demonstrating methods to automate genome finishing for bacteria using single molecule real-time sequencing.[30][31][32] In 2013, scientists estimated that the majority of bacterial and archaeal genomes could be fully sequenced and assembled to closure using PacBio long reads.[33]

Several papers published by researchers at Pacific Biosciences demonstrated that the sequencing instrument can be used to collect data on methylation, DNA damage, and other epigenetic information.[34][35][36] The polymerase that performs the sequencing reaction in the zero-mode waveguides produces kinetic data that can be used to distinguish base modifications.[37] In October 2012, scientists used SMRT sequencing to generate the methylomes of six bacteria, reporting their results in a paper in Nucleic Acids Research.[38]

With increasing read length and throughput, mammalian studies increased using the product. In April 2012, scientists from Pacific Biosciences, the University of California, and other institutes used SMRT sequencing to prove the validity of activating internal tandem duplication mutations in FLT3 as a therapeutic target in acute myeloid leukemia.[39] Their findings were published in the journal Nature.[40] In August 2012, scientists at the Broad Institute published a paper reporting the findings of their evaluation of the Pacific Biosciences sequencer for SNP calling and discovery.[41] Scientists reported in Genome Research in October 2012 the use of the PacBio platform to sequence the full repeat expansion in the FMR1 gene responsible for Fragile X Syndrome.[42]

A paper published in December 2012 offered the first demonstration of how to generate sequence data with the PacBio sequencer with no library preparation.[43]

In 2013, scientists published papers demonstrating the use of PacBio sequencing to analyze transcriptomes, showing that long reads were able to fully capture complete isoforms.[44][45]

See also[edit]

References[edit]

  1. ^ a b c d Businessweek (Dec 3, 2009) "WEF Announces 2010 Tech Pioneers"
  2. ^ Nature Methods (2010)
  3. ^ http://www.genomeweb.com/sequencing/pacbio-reveals-beta-system-specs-rs-says-commercial-release-track-first-half-201
  4. ^ a b http://www.genomeweb.com/sequencing/pacbio-ships-first-two-commercial-systems-order-backlog-grows-44
  5. ^ a b c http://nextgenseek.com/2013/04/pacbio-launches-pacbio-rs-ii-sequencer/
  6. ^ a b c http://www.genomeweb.com/sequencing/new-products-pacbios-rs-ii-cufflinks
  7. ^ Pacific Biosciences to Partner With Roche on In Vitro Diagnostics Products
  8. ^ Wall Street Journal (Mar 9, 2010) "Sizing Up Promising Young Firms"
  9. ^ San Francisco Chronicle (Dec 4, 2009) "World Economic Forum honors Bay Area techies"
  10. ^ The Scientist Magazine (1 Dec 2010) "Top Ten Innovations 2010"
  11. ^ Reuters (Apr 5, 2010) "Factbox: Companies riding the genome wave"
  12. ^ Technology Review (2010, 2011) Company profile on Pacific Biosciences
  13. ^ Technology Review (2010) "Technology Review's 50 Most Innovative Companies"
  14. ^ Ewing Marion Kauffman Foundation (Mar 12, 2010) "Two Postdoctural Entrepreneurs are Recognized for Excellence"
  15. ^ Pacific Biosciences of California
  16. ^ Genome Web (Feb 23, 2010) "PacBio Names First 10 Customers for $695,000 Single-Molecule Sequencer; First Shipments Slated for Q2"
  17. ^ GATC Biotech to be First European Service Provider for PacBio RS
  18. ^ Pacific Biosciences web page about their Analysis product
  19. ^ http://www.genomeweb.com/sequencing/new-products-pacbios-smrt-analysis-14
  20. ^ http://www.genengnews.com/gen-news-highlights/finishing-genomes-with-hgap/81248321/
  21. ^ http://www.nature.com/nmeth/journal/v10/n6/full/nmeth.2474.html
  22. ^ Genome Web (May 10, 2010) "Pacific Biosciences Team Demonstrates Method for Directly Detecting Methylation During SMRT Sequencing"
  23. ^ The methylomes of six bacteria
  24. ^ Pacific Biosciences Introduces New Chemistry With Longer Read Lengths to Detect Novel Features in DNA Sequence and Advance Genome Studies of Large Organisms
  25. ^ PacBio Releases New Chemistry
  26. ^ http://www.sciencemag.org/content/323/5910/133.abstract
  27. ^ http://www.nature.com/nature/journal/v464/n7291/full/nature08925.html
  28. ^ http://www.nejm.org/doi/full/10.1056/NEJMoa1012928#t=article
  29. ^ http://www.nejm.org/doi/full/10.1056/NEJMoa1106920?query=featured_home&#t=article
  30. ^ http://genome.cshlp.org/content/early/2012/07/24/gr.141515.112.full.pdf
  31. ^ http://www.nature.com/nbt/journal/v30/n7/full/nbt.2288.html
  32. ^ http://www.nature.com/nbt/journal/v30/n7/full/nbt.2280.html
  33. ^ http://genomebiology.com/2013/14/9/R101/abstract
  34. ^ http://www.genomeintegrity.com/content/2/1/10
  35. ^ http://nar.oxfordjournals.org/content/early/2011/12/07/nar.gkr1146.full
  36. ^ http://www.nature.com/nmeth/journal/v9/n1/full/nmeth.1779.html
  37. ^ http://www.genomeweb.com/sequencing/pacbio-u-chicago-develop-single-molecule-hydroxymethylation-sequencing-technique
  38. ^ http://nar.oxfordjournals.org/content/early/2012/10/02/nar.gks891.abstract?keytype=ref&ijkey=5wszQKtd4ssMjGh
  39. ^ http://www.genengnews.com/gen-news-highlights/investigators-validate-flt3-kinase-domain-as-acute-myeloid-leukemia-target/81246630/
  40. ^ http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11016.html
  41. ^ http://www.biomedcentral.com/1471-2164/13/375/abstract
  42. ^ http://genome.cshlp.org/content/early/2012/10/11/gr.141705.112.abstract
  43. ^ http://www.biotechniques.com/BiotechniquesJournal/2012/December/Direct-sequencing-of-small-genomes-on-the-Pacific-Biosciences-RS-without-library-preparation/biotechniques-338089.html
  44. ^ http://www.nature.com/nbt/journal/v31/n11/full/nbt.2705.html
  45. ^ http://www.pnas.org/content/early/2013/11/25/1320101110.full.pdf

External links[edit]