NGS Evolution
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Next-generation sequencing technologies have rapidly advanced since 2005. Key developments include massively parallel sequencing reactions that enabled sequencing of entire human genomes for less than $1,000 by 2015. While Illumina dominates the market, other platforms like Ion Torrent and PacBio are increasing capabilities. Routine human whole genome sequencing is now used in research and medicine, enabling new opportunities like liquid biopsies and single-cell analysis. However, data storage and analysis remain challenges due to the large volumes of sequencing data.
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NGS Evolution
- 1. Next-generation sequencing (NGS) 2020 Christian Frech Bioinformatics Core Unit CCRI Retreat Retz April 13, 2015
- 3. Why “next”-generation sequencing? (by 2005, compared to good ol’ Sanger) • Massively parallel – Millions of sequencing reactions vs. 96 wells • Therefore much cheaper – >1 Mio. $ vs. 25 Mio. $ for human genome • Shorter reads – 100 bp vs. 700 bp • Higher error rate – 1-2% error rate vs. 0.5%
- 4. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 5. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 6. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 7. Genome Analyzer II 50bp reads, 3 Gb / run 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 8. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 9. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 10. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 11. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 12. 2005 20102006 2007 2008 2009 454 Solexa GA1 HiSeq 2000 PacBio Complete Genomics First Illumina human genome + First tumor/normal pair Helicos single-molecule 454 Watson Genome Illumina GA2 Helicos human genome SOLiD
- 13. Status quo 2010 • Illumina starts dominating NGS market due to rapid improvements of their platform – 200 Gb per run, >$10k for human genome • Roche 454 10x more expensive, but still valued for longer read length (~400 bp) • Single-molecule sequencing platforms (Helicos, PacBio) niche players
- 14. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 15. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 16. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 17. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 18. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 19. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 20. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 21. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 22. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore bact. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 23. 2010 20152011 2012 2013 2014 HiSeq X Ten MiSeq Nanopore euk. genome Nanopore early access Ion Torrent PGM PacBio human genome BGI acquires Complete Genomics Helicos bancrupt Ion Proton 454 shutdown
- 24. Status quo 2015 • Illumina clear market leader – 80-90% market share – 1,500 Gb per run, >$1k for human genome • Most serious competitor is Ion Proton – Behind schedule with Chip upgrade • Single-molecule sequencers on the rise – PacBio, Oxford Nanopore
- 26. • Routine human WGS in research and clinic – <$500 EUR per sample – Sequencing-as-a-service – Phasing available for little extra money • Exploding market for liquid biopsies driven by cheap targeted sequencing and “precision medicine” initiatives • Single-cell sequencing method of choice to study tumor heterogeneity • RNA-seq with negligible costs for sequencing – <$20/sample; cost for library prep will dominate – Microarrays are dead (…likely not only for gene expression analysis) • Single-molecule sequencers still in niche – Limited throughput, high error rates – Rapid amplicon sequencing (results within minutes in the lab) 2015 2020 ?
- 27. Implications for the CCRI • New research opportunities – WGS to characterize “atypical” tumors – Liquid biopsies for solid tumors, disease monitoring – Single-cell sequencing (RNA, DNA) • Established assays will be increasingly complemented/challenged by cheap sequencing alternatives – PCR, FISH, MLPA, SNP-arrays – WGS as one-stop solution for mutation/CNA/SV detection • Data volumes will grow significantly – Efficient computational pipelines utilizing all available hardware – Storage capacity – Cloud computing
- 28. Thank you!
- 29. SOLiD 2015