Grant Number:	5R33CA174575-03 Interpret this number
Primary Investigator:	Ji, Hanlee
Organization:	Stanford University
Project Title:	Oligonucleotide-Selective Sequencing for Integrated and Rapid Cancer Genome Analy
Fiscal Year:	2015

DESCRIPTION (provided by applicant): Personalized cancer medicine involves identifying clinically actionable cancer mutations and genomic aberrations in any given tumor. As we recently published in the November 2011 issue of Nature Biotechnology, Oligonucleotide-Selective Sequencing (OS-Seq) is a novel targeted resequencing approach that fundamentally improves the detection of cancer mutations from clinical samples. This technology has the potential for enabling the rapid, accurate detection of cancer mutations for both translational research studies and potentially, "personalized" cancer diagnostics. OS-Seq provides a number of advantages to make personalized cancer analysis accessible, rapid, robust and accurate. The overall workflow is simplified such that the majority of preparative steps take place on a standard fluidics device and the actual experimental manipulation is limited. The performance is improved compared to the current commercially available methods for targeted, gene-specific cancer sequencing analysis. Based on our empirical analysis and subsequent refinements in designing capture probes, we demonstrate very specific capture of genomic targets with less variance than other methods. We achieve a high level of sequencing coverage on our targets that permit sensitive and specific detection of cancer mutations. With recent improvements in sequencing technology speed, OS-Seq can potentially be adapted to analyze large number of cancer genes in a matter of days which includes the time that genomic DNA is extracted from a biopsy to the completion of the targeted sequencing run. This holds the possibility of rapidly identifying cancer mutations from clinical samples. Our proposal is focused on development of the OS-Seq technology for identifying cancer mutations, rearrangements, copy number alterations and potential cancer-related infectious agents from clinical tumor samples. To achieve this goal, we will develop key aspects of OS-Seq technology for integrated detection of cancer mutations and genomic aberrations with simple protocols that are reliable, rapid and with high accuracy.




Profiling diverse sequence tandem repeats in colorectal cancer reveals co-occurrence of microsatellite and chromosomal instability involving Chromosome 8.
Authors: Shin G. , Greer S.U. , Hopmans E. , Grimes S.M. , Lee H. , Zhao L. , Miotke L. , Suarez C. , Almeda A.F. , Haraldsdottir S. , et al. .
Source: Genome medicine, 2021-09-06; 13(1), p. 145.
EPub date: 2021-09-06.
PMID: 34488871
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Covalent "Click Chemistry"-Based Attachment of DNA onto Solid Phase Enables Iterative Molecular Analysis.
Authors: Lau B.T. , Ji H.P. .
Source: Analytical chemistry, 2019-02-05; 91(3), p. 1706-1710.
EPub date: 2019-01-22.
PMID: 30652472
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A robust targeted sequencing approach for low input and variable quality DNA from clinical samples.
Authors: So A.P. , Vilborg A. , Bouhlal Y. , Koehler R.T. , Grimes S.M. , Pouliot Y. , Mendoza D. , Ziegle J. , Stein J. , Goodsaid F. , et al. .
Source: NPJ genomic medicine, 2018; 3, p. 2.
EPub date: 2018-01-15.
PMID: 29354287
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Robust Multiplexed Clustering and Denoising of Digital PCR Assays by Data Gridding.
Authors: Lau B.T. , Wood-Bouwens C. , Ji H.P. .
Source: Analytical chemistry, 2017-11-21; 89(22), p. 11913-11917.
EPub date: 2017-11-07.
PMID: 29083143
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Single-Color Digital PCR Provides High-Performance Detection of Cancer Mutations from Circulating DNA.
Authors: Wood-Bouwens C. , Lau B.T. , Handy C.M. , Lee H. , Ji H.P. .
Source: The Journal of molecular diagnostics : JMD, 2017 Sep; 19(5), p. 697-710.
EPub date: 2017-08-14.
PMID: 28818432
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CRISPR-Cas9-targeted fragmentation and selective sequencing enable massively parallel microsatellite analysis.
Authors: Shin G. , Grimes S.M. , Lee H. , Lau B.T. , Xia L.C. , Ji H.P. .
Source: Nature communications, 2017-02-07; 8, p. 14291.
EPub date: 2017-02-07.
PMID: 28169275
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A genome-wide approach for detecting novel insertion-deletion variants of mid-range size.
Authors: Xia L.C. , Sakshuwong S. , Hopmans E.S. , Bell J.M. , Grimes S.M. , Siegmund D.O. , Ji H.P. , Zhang N.R. .
Source: Nucleic acids research, 2016-09-06; 44(15), p. e126.
EPub date: 2016-06-20.
PMID: 27325742
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Haplotyping germline and cancer genomes with high-throughput linked-read sequencing.
Authors: Zheng G.X. , Lau B.T. , Schnall-Levin M. , Jarosz M. , Bell J.M. , Hindson C.M. , Kyriazopoulou-Panagiotopoulou S. , Masquelier D.A. , Merrill L. , Terry J.M. , et al. .
Source: Nature biotechnology, 2016 Mar; 34(3), p. 303-11.
EPub date: 2016-02-01.
PMID: 26829319
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Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer.
Authors: Nadauld L.D. , Garcia S. , Natsoulis G. , Bell J.M. , Miotke L. , Hopmans E.S. , Xu H. , Pai R.K. , Palm C. , Regan J.F. , et al. .
Source: Genome biology, 2014-08-27; 15(8), p. 428.
EPub date: 2014-08-27.
PMID: 25315765
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A programmable method for massively parallel targeted sequencing.
Authors: Hopmans E.S. , Natsoulis G. , Bell J.M. , Grimes S.M. , Sieh W. , Ji H.P. .
Source: Nucleic acids research, 2014 Jun; 42(10), p. e88.
EPub date: 2014-04-29.
PMID: 24782526
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Identification of Insertion Deletion Mutations from Deep Targeted Resequencing.
Authors: Natsoulis G. , Zhang N. , Welch K. , Bell J. , Ji H.P. .
Source: Journal of data mining in genomics & proteomics, 2013-07-02; 4(3), .
PMID: 24511426
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Targeted deep resequencing of the human cancer genome using next-generation technologies.
Authors: Myllykangas S. , Ji H.P. .
Source: Biotechnology & genetic engineering reviews, 2010; 27, p. 135-58.
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