Pacific Biosciences

Coordinates: 37°28′43″N 122°09′03″W / 37.4787°N 122.1507°W / 37.4787; -122.1507 (headquarters)

Pacific Biosciences of California, Inc.
Public company
Traded as NASDAQ: PACB
Russell 2000 Component
Industry Biotechnology
Founded 2004 (2004)
Headquarters Menlo Park, CA, United States
Key people
 Michael Hunkapiller, Chairman, CEO, and President
Website www.pacificbiosciences.com

Pacific Biosciences of California, Inc. is a biotechnology company founded in 2004 that develops and manufactures systems for gene sequencing and some novel real time biological observation.[1][2] PacBio describes its platform as single molecule real time sequencing (SMRT), based on the properties of zero-mode waveguides. The company's first commercial product, the PacBio RS, was sold to a limited set of customers in 2010 and was commercially released in early 2011.[3][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 US$75,000,000 in the deal.[7][8] In 2015, the company launched a new sequencing instrument called the Sequel System with approximately 7-fold greater capacity than the PacBio RS II.[9][10]

History

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 US$400,000,000 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.[11] Key investors included Mohr Davidow Ventures, Kleiner, Perkins, Caufield & Byers, Alloy Ventures, and Wellcome Trust.[1]

Recognitions

The company received the Technology Pioneer Award from the World Economic Forum in 2009.[1][12]

In 2010, The Scientist named the company and their first product the top life science innovation of the year,[13] and the company received the 2010 Advanced Sequencing Technology Award from the National Human Genome Research Institute.[14] Technology Review magazine included them in their list of the top 50 most innovative companies for both 2010 and 2011.[15] 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.[16]

Going public

In an initial public offering on October 27, 2010, Pacific Biosciences sold 12,500,000 shares at a price of $16 per share and raised approximately $200 million. The shares trade on NASDAQ under the symbol PACB.[17]

Products

Sequencing instruments

A PacBio RSII sequencer
Pacific Biosciences Sequel Sequencer

The company’s first scientific instrument, called the “PacBio RS”, was released to a limited set of eleven customers in late 2010.[18] Sequencing provider GATC Biotech was selected by Pacific Biosciences as its first European service provider in late 2010.[19] 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] In September 2015, the company announced the launch of a new sequencing instrument, the Sequel System. The sequencer has increased capacity with 1 million zero-mode waveguides compared to 150,000 in the PacBio RS II, and is approximately one-third the size and one-half the price of the PacBio RS II.[20][21] Pacific Biosciences said it would ship about 10 of the new instruments in the final quarter of 2015.[22]

In May 2010, an article in Nature Methods showed that PacBio's instrument can detect methylation of DNA strands without altering the DNA.[23] In 2012 scientists used SMRT sequencing to generate full bacterial methylomes.[24]

Reagents and SMRT Cells

Further information: Single molecule real time sequencing

To use either instrument, customers must also purchase reagent packs for DNA preparation and sequencing and small consumables called “SMRT Cells”. Each RS cell is slightly less than one centimeter square and contains tens of thousands of zero-mode waveguides. Each Sequel cell is about 2.5 cm square and contains one million zero-mode waveguides. The RS cells are sold in packs of eight and Sequel cells in packs of four.

On 19 Sep 2018, PacBio released the Sequel 6.0 chemistry, synchronizing the chemistry version with the software version. Performance is contrasted for large-insert libraries and high molecular weight DNA versus shorter-insert libraries below ~15,000 bases in length. For larger templates average read lengths are up to 30,000 bases. For shorter-insert libraries, average read length are up to 100,000 bases while reading the same molecule in a circle. The latter shorter-insert libraries then yield up to 50 billion bases from a single SMRT® Cell.[25]

Software

Their secondary analysis bioinformatics product for the RS, called “SMRT Analysis”, was open source.[26] For the Sequel system the secondary analysis software was reorganized as the "SMRT Link" application. In 2013, the company released new bioinformatics tools for automated genome assembly (HGAP) and finishing to 99.999% accuracy (Quiver).[27][28][29]

Key publications

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.[30] 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.[31]

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.[32] 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.[33] 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.[34][35][36] In 2013, scientists estimated that the majority of bacterial and archaeal genomes could be fully sequenced and assembled to closure using PacBio long reads.[37]

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.[38][39][40] The polymerase that performs the sequencing reaction in the zero-mode waveguides produces kinetic data that can be used to distinguish base modifications.[41] In October 2012, scientists used SMRT sequencing to generate the methylomes of six bacteria, reporting their results in a paper in Nucleic Acids Research.[24]

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.[42] Their findings were published in the journal Nature.[43] 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.[44] 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.[45]

A paper published in December 2012 offered the first demonstration of how to generate sequence data with the PacBio sequencer with no library preparation.[46]

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.[47][48]

References

  1. 1 2 3 4 Businessweek (Dec 3, 2009) "WEF Announces 2010 Tech Pioneers"
  2. ↑ Nature Methods (Apr 15, 2010) "Single-molecule analysis: A ribosome in action"
  3. ↑ GenomeWeb (Dec 7, 2010) "PacBio Reveals Beta System Specs for RS; Says Commercial Release is on Track for First Half of 2011"
  4. 1 2 GenomeWeb (May 3, 2011) "PacBio Ships First Two Commercial Systems; Order Backlog Grows to 44"
  5. 1 2 Next Gen Seq (Apr 11, 2013) "PacBio Launches PacBio RS II Sequencer"
  6. 1 2 GenomeWeb (Apr 16, 2013) "New Products: PacBio's RS II; Cufflinks"
  7. ↑ Pacific Biosciences to Partner With Roche on In Vitro Diagnostics Products Archived September 25, 2013, at the Wayback Machine.
  8. ↑ The Motley Fool (Sep 25, 2013) "Pacific Biosciences Rockets on Roche Diagnostics Deal"
  9. ↑ https://www.genomeweb.com/business-news/pacbio-launches-higher-throughput-lower-cost-single-molecule-sequencing-system
  10. ↑ http://www.bio-itworld.com/2015/9/30/pacbio-announces-sequel-sequencing-system.aspx
  11. ↑ Wall Street Journal (Mar 9, 2010) "Sizing Up Promising Young Firms"
  12. ↑ San Francisco Chronicle (Dec 4, 2009) "World Economic Forum honors Bay Area techies"
  13. ↑ The Scientist (1 Dec, 2010) "Top Ten Innovations 2010"
  14. ↑ Reuters (Apr 5, 2010) "Factbox: Companies riding the genome wave"
  15. ↑ Technology Review (2010, 2011) "Company Profile: Pacific Biosciences"
  16. ↑ Ewing Marion Kauffman Foundation (Mar 12, 2010) "Two Postdoctural Entrepreneurs are Recognized for Excellence" Archived June 21, 2010, at the Wayback Machine.
  17. ↑ Renaissance Capital (Oct 30, 2010) "Pacific Biosciences of California (PACB)"
  18. ↑ Genome Web (Feb 23, 2010) "PacBio Names First 10 Customers for $695,000 Single-Molecule Sequencer; First Shipments Slated for Q2"
  19. ↑ GenomeWeb (Sep 21, 2010) "GATC Biotech to be First European Service Provider for PacBio RS"
  20. ↑ http://www.bio-itworld.com/2015/9/30/pacbio-announces-sequel-sequencing-system.aspx
  21. ↑ http://www.pacb.com/blog/introducing-the-sequel-system-the-scalable-platform-for-smrt-sequencing/
  22. ↑ https://www.genomeweb.com/business-news/pacbio-launches-higher-throughput-lower-cost-single-molecule-sequencing-system
  23. ↑ GenomeWeb (May 10, 2010) "Pacific Biosciences Team Demonstrates Method for Directly Detecting Methylation During SMRT Sequencing"
  24. 1 2 Nucleic Acids Research (Oct 2, 2012) "The methylomes of six bacteria"
  25. ↑ https://twitter.com/PacBio/status/1042417439441645570
  26. ↑ Pacific Biosciences (Feb 23, 2015) "Analysis"
  27. ↑ GenomeWeb (Jan 29, 2013) "New Products: PacBio's SMRT Analysis 1.4"
  28. ↑ Genetic Engineering & Biotechnology News (May 6, 2013) "Finishing Genomes with HGAP"
  29. ↑ Nature Methods (May 5, 2013) "Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data"
  30. ↑ Science (Nov 20, 2008) "Real-Time DNA Sequencing from Single Polymerase Molecules"
  31. ↑ Nature (Apr 15, 2010) "Real-time tRNA transit on single translating ribosomes at codon resolution"
  32. ↑ New England Journal of Medicine (Jan 6, 2011) "The Origin of the Haitian Cholera Outbreak Strain"
  33. ↑ New England Journal of Medicine (Aug 25, 2011) "Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany"
  34. ↑ Genome Research (Jul 24, 2012) "Finished bacterial genomes from shotgun sequence data"
  35. ↑ Nature Biotechnology (Jul 1, 2012) "A hybrid approach for the automated finishing of bacterial genomes"
  36. ↑ Nature Biotechnology (Jul 1, 2012) "Hybrid error correction and de novo assembly of single-molecule sequencing reads"
  37. ↑ Genome Biology (Sep 13, 2013) "Reducing assembly complexity of microbial genomes with single-molecule sequencing"
  38. ↑ Genome Integrity (Dec 20, 2011) "Direct Detection and Sequencing of Damaged DNA Bases"
  39. ↑ Nucleic Acids Research (Dec 7, 2011) "Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing"
  40. ↑ Nature Methods (Nov 20, 2011) "Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine"
  41. ↑ GenomeWeb (Dec 6, 2011) "PacBio, U Chicago Develop Single-Molecule Hydroxymethylation Sequencing Technique"
  42. ↑ Genetic Engineering & Biotechnology News (Apr 16, 2012) "Investigators Validate FLT3 Kinase Domain as Acute Myeloid Leukemia Target"
  43. ↑ Nature (Apr 15, 2012) "Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia"
  44. ↑ BMC Genomics (Aug 5, 2012) "Pacific biosciences sequencing technology for genotyping and variation discovery in human data"
  45. ↑ Genome Research (Oct 11, 2012) "Sequencing the unsequenceable: Expanded CGG-repeat alleles of the fragile X gene"
  46. ↑ Biotechniques (Dec 2012) "Direct sequencing of small genomes on the Pacific Biosciences RS without library preparation"
  47. ↑ Nature Biotechnology (Oct 13, 2013) "A single-molecule long-read survey of the human transcriptome"
  48. ↑ Proceedings of the National Academy of Scientists USA (Nov 26, 2013) "Characterization of the human ESC transcriptome by hybrid sequencing"
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