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JUN 20, 2019 10:30 AM PDT

The Massively Parallel Sequencing (MPS) Revolution

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Professor and Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic
    Biography
      David I Smith received his Ph.D. in Biochemistry from the University of Wisconsin in Madison in 1978 studying antibiotic resistance in bacteria. After doing post-doctoral work first at the Albert Einstein College of Medicine and then at the University of California, Irvine, he got his first faculty position at Wayne State University in 1985. In 1996 he joined the Mayo Clinic as a full Professor in the Department of Laboratory Medicine and Pathology. His laboratory studies the common fragile sites which are regions of profound genomic instability that are found in all individuals. His laboratory also studies the various ways that human
      papillomavirus is involved in the generation of different cancers. Dr. Smith is also the Chairman of the Technology Assessment Group for the Mayo Clinic Center for Individualized Medicine. The role of this group is to evaluate new technologies that could have a profound impact on basic research and its' clinical translation. The most exciting technology that has the greatest potential to change both research and clinical practice is next generation sequencing and Dr. Smith and his group have been using this technology to answer scientific questions. The advances in next generation sequencing over the past 10 years have been nothing
      short of incredible and it is now possible to generate terrabases of DNA sequence in a single run of a next generation sequencer. This technology can be utilized in a number of ways from characterizing just a few genes all the way to whole genome sequencing.

    Abstract

    The development of automated DNA sequencers utilizing Sanger sequencing and capillary electrophoresis made it possible to develop the first draft sequences of the human genome. The cost of doing this was hundreds of millions of dollars. However, the advent of technologies which could generate sequences for hundreds of thousands of DNA fragments simultaneously based up MPS heralded a revolution in sequence capability. All first generation MPS platforms utilize one of three approaches to amplify individual DNA molecules to a high copy number followed by sequence interrogation of the original short DNA molecules. The most successful platform for MPS was developed by the company Illumina and they have increased sequence output from 1 gigabase (Gb) to over 6 terrabases (Tbs) in less than 13 years. Currently the cost for generating sufficient DNA sequence for whole genome sequencing (WGS) of an individual human is just $375. However, the total cost for WGS is considerably higher when one factors in library preparation, sequencing, assembling and interpreting that genome sequence, and data storage. There is an alternative platform developed by Complete Genomics based upon a non-PCR based technology to amplify DNA templates. This platform is now being utilized by BGI and they have a machine which is capable of generating 7 Tbs of sequence data per run. On this platform the total cost for WGS is now just $600 and BGI is developing larger machines in the hope of bringing WGS total costs down to just $100. First generation MPS can now be utilized for WGS, but also for whole exome sequencing, targeted genome sequencing, transcriptome sequencing, methylation sequencing as well as metagenomic sequencing. All of these will completely transform research and its’ clinical translation. Second generation MPS is based upon the analysis of single unamplified DNA molecules and can generate DNA sequences that can be 100 kilobases in length or greater. In my talk I will discuss the history of first generation MPS and how this revolution represents an important technological singularity.

    Learning Objectives: 

    1. To understand the revolution that has occurred in DNA sequencing based upon technologies that utilize massively parallel sequencing
    2. To understand how these technologies will completely transform clinical practice.


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