Biology Department Seminar

SMASH is a technology for sequencing a human size genome of 6 Gigabases (including both haplotypes) without using any prior sequence information. We have aimed the technology for eventually (e.g., in less than a decade) achieving a competitively low cost for each genome sequence produced (e.g. US$1000 or less), while assuring a high quality (e.g., standard of “high quality draft sequence” similar to the mouse genome sequence published in December 2002). This technology is hoped to play a significant disruptive role in the future predictive personalized biomedicine as well as other areas of biotech industries. These goals require successful integration of three different component technologies: (1) Optical Mapping to create Ordered Restriction Maps with respect to an enzyme, (2) Hybridization of a pool of oligonucleotide probes (LNA probes) with Single Genomic dsDNAs, and (3) Algorithms to solve “localized versions” of PSBH (Positional Sequencing by Hybridization) problems over the whole genome. Unlike many of its competitors, the technology works with small amount of genomic materials, operates top-down, employs a Bayesian algorithm to create haplotypic sequence assembly without an auxiliary shotgun assembler, tolerates noise in the data well and is cost-effective at multiple scales. By construction, it avoids errors due to hompolymeric runs, haplotypic ambiguities and large-scale rearrangement errors. Its scientific feasibility has been demonstrated through many important algorithmic, chemical, and mathematical innovations over the last two years, further reassuring the soundness of the principles, science, and strategy for technology development.