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MASSIVELY PARALLEL HIGH THROUGHPUT, LOW COST SEQUENCING

Award Number: P01HG003022
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/14/2004
PERIOD OF PERFORMANCE END DATE: 03/31/2006

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MASSIVELY PARALLEL HIGH THROUGHPUT, LOW COST SEQUENCING - DESCRIPTION: (provided by applicant) Background: Large-scale genomic sequencing currently requires high cost equipment and is labor intensive. The throughput of conventional sequencing has grown inadequate in fulfilling the escalating demands for genomic sequence. Understanding the intricacies of human genetic organization and how it relates to human health and inheritance, requires genomic-level comparative analyses that cannot currently be performed due to the lack of sequence information. The 454 Corporation has developed a massively parallel, high-throughput sequencing instrument that combines simultaneous sequencing in hundreds of thousands of picoliter-scale reaction wells, with high-powered bioinformatics. The method does not require an exponential scale up in effort or cost, despite exponential increases in genome size. The effort and cost of conventional sequencing scales up proportionately with the size of the genome. The 454 approach will be low cost, and make sequencing large genomes available to a wide variety of laboratories. Specific Aims: In this Program we will (i) Construct a robust double-ended sequencing method that generates short sequences from both ends of each individual fragment (ii) Develop a robust sequence assembly tool appropriate for double-ended sequencing (iii) Prototype the use of our scaled up system, with double-ended sequencing for economical, rapid haplotyping of mammalian organisms. Our Study design incorporates a multi-disciplinary effort across molecular biology, chemistry, engineering, software and bioinformatics groups at 454 Corporation. The molecular biology and sequencing efforts will be lead by the PI, Dr. Kenton L. Lohman. The hardware, fluidics, optics, software and bioinformatics efforts will be lead by co-PI, Dr. Marcel Margulies. We will be taking advantage of current 454 infrastructure, and key personnel. Relevance: There is a growing need across the research, pharmaceutical and clinical communities for low-cost, high throughput genomic sequencing. Comparative genomics, SNP and haplotype analyses have shown tremendous potential to rapidly characterize individual susceptibilities to many classes of chronic and acute diseases and disorders. Current costs of whole genome sequencing can only be borne by large institutions. The cost of automated sample preparation and sequencing, scales up proportionately to the size of the genome being sequenced. The 454 Sequencing system simultaneously analyzes millions of fragments in massively parallel sequencing of mammalian organisms. The use of massively parallel sequencing and bioinformatics analysis creates a low cost, high throughput sequencing system.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2005 ( Subtotal = $1,243,263 )
2005	2005	454 LIFE SCIENCES CORPORATION	20 COMMERCIAL STREET	BRANFORD	CT	06405	SOUTH CENTRAL CT	USA	Human Genome Research	000	2	3/28/2005	NON-COMPETING CONTINUATION	$1,180,502
2005	2005	454 LIFE SCIENCES CORPORATION	20 COMMERCIAL STREET	BRANFORD	CT	06405	SOUTH CENTRAL CT	USA	Human Genome Research	001	1	3/7/2005	SUPPLEMENT FOR EXPANSION	$62,761
														Subtotal = $1,243,263

Issue Date FY: 2004 ( Subtotal = $981,940 )
2004	2004	454 LIFE SCIENCES CORPORATION	20 COMMERCIAL STREET	BRANFORD	CT	06405	SOUTH CENTRAL CT	USA	Human Genome Research	000	1	5/10/2004	NEW	$981,940
														Subtotal = $981,940

Grand Total All Awards = $2,225,203

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MASSIVELY PARALLEL HIGH THROUGHPUT, LOW COST SEQUENCING

Award Number: P01HG003022

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/14/2004

PERIOD OF PERFORMANCE END DATE: 03/31/2006

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