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.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center (P50)
Project #
1P50HG007735-01
Application #
8914814
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
Name
Stanford University
Department
Type
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304
Karczewski, Konrad J; Snyder, Michael P (2018) Integrative omics for health and disease. Nat Rev Genet 19:299-310
Rappoport, Nadav; Toung, Jonathan; Hadley, Dexter et al. (2018) A genome-wide association study identifies only two ancestry specific variants associated with spontaneous preterm birth. Sci Rep 8:226
Mezger, Anja; Klemm, Sandy; Mann, Ishminder et al. (2018) High-throughput chromatin accessibility profiling at single-cell resolution. Nat Commun 9:3647
Zamanighomi, Mahdi; Lin, Zhixiang; Daley, Timothy et al. (2018) Unsupervised clustering and epigenetic classification of single cells. Nat Commun 9:2410
Chan, Charles K F; Gulati, Gunsagar S; Sinha, Rahul et al. (2018) Identification of the Human Skeletal Stem Cell. Cell 175:43-56.e21
Tilgner, Hagen; Jahanbani, Fereshteh; Gupta, Ishaan et al. (2018) Microfluidic isoform sequencing shows widespread splicing coordination in the human transcriptome. Genome Res 28:231-242
Keating, Brendan J; Pereira, Alexandre C; Snyder, Michael et al. (2018) Applying genomics in heart transplantation. Transpl Int 31:278-290
Satpathy, Ansuman T; Saligrama, Naresha; Buenrostro, Jason D et al. (2018) Transcript-indexed ATAC-seq for precision immune profiling. Nat Med 24:580-590
Calo, Eliezer; Gu, Bo; Bowen, Margot E et al. (2018) Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders. Nature 554:112-117
Chen, Xingqi; Litzenburger, Ulrike M; Wei, Yuning et al. (2018) Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity. Nat Commun 9:4590

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