Over the past four years, a remarkable sequencing technology explosion has occurred, opening many new avenues of biological experimentation and discovery. We describe a platform for large- scale sequencing and analysis that extends the incredible potential of next-generation sequencing to transform biomedical research and significantly impact medical practice. Our eight specific aims are intertwined across six major research areas that overall address the NHGRI mission and provide an interdisciplinary approach that is already producing medically relevant results in the areas of cancer genomics, heritable disease, and microbial/metagenomics. Our platform offers a consistently cost-effective approach to sequencing-related research projects and we have established a scalable incoming sample pipeline that can intake and track >40,000 samples per year into a flexible and innovative sequencing pipeline. Equally scalable are our LIMS and analysis pipeline capabilities, having established systems that processed several hundred cancer cases through whole genome sequencing and analysis in the last year alone, along with multiple other project types. We describe a research plan that will further our explorations of human health and disease, in a more comprehensive manner than ever before, and will investigate third-generation sequencing technologies, incorporating their unique attributes and integrating them to our production repertoire. One important aspect of our proposed work includes efforts to begin translating our discoveries and procedures into the clinical setting, effectively setting the stage for genomic diagnosis and personalized medicine. This important transition will be required to bring DNA sequencing to clinical medicine, and our innovative combination of sequencing technology, data analysis, and outstanding clinical collaborators increase the potential for success. Overall, we are enthusiastic about the future of genome sequencing at high scale, and we combine years of success in DNA sequencing and analysis with the necessary collaboration expertise, infrastructure support, and shared vision with NHGRI to make significant progress on these aims in the next four years.

Public Health Relevance

The potential for DNA sequencing to transform medical practice and change our understanding of disease has never been higher. Our group combines years of experience in DNA sequencing with key clinical researchers to address important questions in patient care and outcome. These early efforts will translate to a revolution in medicine, centered around DNA-based diagnostics including whole genome sequencing.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54HG003079-11S1
Application #
8918235
Study Section
Special Emphasis Panel (ZHG1-HGR-P (O2))
Program Officer
Felsenfeld, Adam
Project Start
2003-11-10
Project End
2015-10-31
Budget Start
2014-09-17
Budget End
2014-10-31
Support Year
11
Fiscal Year
2014
Total Cost
$114,868
Indirect Cost
$23,340
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
White, Nicole M; Cabanski, Christopher R; Silva-Fisher, Jessica M et al. (2014) Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer. Genome Biol 15:429
Marmoset Genome Sequencing and Analysis Consortium (2014) The common marmoset genome provides insight into primate biology and evolution. Nat Genet 46:850-7
Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles et al. (2014) Integrated analysis of germline and somatic variants in ovarian cancer. Nat Commun 5:3156
Bellott, Daniel W; Hughes, Jennifer F; Skaletsky, Helen et al. (2014) Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature 508:494-9
Jacoby, M A; De Jesus Pizarro, R E; Shao, J et al. (2014) The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia. Leukemia 28:1242-51
Hung, John E; Mill, Christopher P; Clifton, Sandra W et al. (2014) Draft Genome Sequence of Acetobacter aceti Strain 1023, a Vinegar Factory Isolate. Genome Announc 2:
Mangiola, Stefano; Young, Neil D; Sternberg, Paul W et al. (2014) Analysis of the transcriptome of adult Dictyocaulus filaria and comparison with Dictyocaulus viviparus, with a focus on molecules involved in host-parasite interactions. Int J Parasitol 44:251-61
Mardis, Elaine R (2014) Sequencing the AML genome, transcriptome, and epigenome. Semin Hematol 51:250-8
Xie, Mingchao; Lu, Charles; Wang, Jiayin et al. (2014) Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 20:1472-8
Hoadley, Katherine A; Yau, Christina; Wolf, Denise M et al. (2014) Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin. Cell 158:929-44

Showing the most recent 10 out of 104 publications