Abstract

Despite the rapidly increasing capacity to sequence human genomes, our incomplete ability to read and interpret the information content in genomes and epigenomes remain a central challenge. A comprehensive set of regulatory events across a genome - the regulome - is needed to make full use of genomic information, but is currently out of reach for practically all clinical applications and many biological systems The proposed Center will develop technologies that greatly increase the sensitivity, speed, and comprehensiveness of understanding genome regulation. We will develop new technologies to interrogate the transactions between the genome and regulatory factors, such as proteins and noncoding RNAs, and integrate variations in DNA sequences and chromatin states over time and across individuals. Novel molecular engineering and biosensor strategies are deployed to encapsulate the desired complex DNA transformations into the probe system, such that the probe system can be directly used on very small human clinical samples and capture genome-wide information in one or two steps. These technologies will be applied to clinical samples and workflows in real time to exercise their robustness and reveal for the first time epigenomic dynamics of human diseases during progression and treatment. These technologies will be broadly applicable to many biomedical investigations, and the Center will disseminate the technologies via training and diverse means.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center (P50)
Project #
1P50HG007735-01
Application #
8914813
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Pazin, Michael J
Project Start
2014-09-01
Project End
2019-06-30
Budget Start
2014-09-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304

  Publications

Gate, Rachel E; Cheng, Christine S; Aiden, Aviva P et al. (2018) Genetic determinants of co-accessible chromatin regions in activated T cells across humans. Nat Genet 50:1140-1150
Prazsák, István; Tombácz, Dóra; Sz?cs, Attila et al. (2018) Full Genome Sequence of the Western Reserve Strain of Vaccinia Virus Determined by Third-Generation Sequencing. Genome Announc 6:
Boyle, Evan A; Pritchard, Jonathan K; Greenleaf, William J (2018) High-resolution mapping of cancer cell networks using co-functional interactions. Mol Syst Biol 14:e8594
Tombácz, Dóra; Sharon, Donald; Sz?cs, Attila et al. (2018) Transcriptome-wide survey of pseudorabies virus using next- and third-generation sequencing platforms. Sci Data 5:180119
Cho, Seung Woo; Xu, Jin; Sun, Ruping et al. (2018) Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element. Cell 173:1398-1412.e22
Oláhová, Monika; Yoon, Wan Hee; Thompson, Kyle et al. (2018) Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder. Am J Hum Genet 102:494-504
Moldován, Norbert; Szucs, Attila; Tombácz, Dóra et al. (2018) Multiplatform next-generation sequencing identifies novel RNA molecules and transcript isoforms of the endogenous retrovirus isolated from cultured cells. FEMS Microbiol Lett 365:
Lu, Zhipeng; Chang, Howard Y (2018) The RNA Base-Pairing Problem and Base-Pairing Solutions. Cold Spring Harb Perspect Biol 10:
Buenrostro, Jason D; Corces, M Ryan; Lareau, Caleb A et al. (2018) Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation. Cell 173:1535-1548.e16
Møller, Henrik Devitt; Mohiyuddin, Marghoob; Prada-Luengo, Iñigo et al. (2018) Circular DNA elements of chromosomal origin are common in healthy human somatic tissue. Nat Commun 9:1069

Showing the most recent 10 out of 117 publications