The goal of Computational Analysis Core B is to manage, analyze, and extract maximum scientific value from the data generated by the investigators of this Program Project. The primary emphasis of Core B will be to assist Program investigators in the analysis of RNA-Seq data and to connect the results of these measurements with prior knowledge to unveil new biology. Importantly, these data will provide a rich source for discovering previously unappreciated shifts in mRNA isoform usage, novel microRNAs and biologically relevant noncoding transcripts. The Core reflects a novel collaboration between researchers spanning two institutions that collectively possess immense expertise and resources in computation and data analysis: The University of Washington (UW) Department of Computer Science &Engineering and Sage Bionetworks, a non-profit biomedical research organization created to revolutionize how researchers approach the complexity of human biological information and the treatment of disease. The vast data sets generated by next-generation sequence technologies create enormous opportunities but also significant challenges. Core B will assure optimal management and interpretation of data obtained from the RNA-Seq studies proposed by Projects 1, 3 and 4 and Core A. These studies will generate RNA-Seq data for both short (e.g., microRNA) and long (e.g., messenger RNA and long noncoding RNA) protocols. As described below. Core Director Dr. Ruzzo (UW), and co-investigators Dr. Brig Mecham and Dr. Adam Margolin (Sage) are exceptionally well qualified to carry out the proposed work, and an existing collaboration with them has already generated interesting findings as described in Project 1 (Blau). In support of the Program, Core B's activities will vary in accordance with the needs of the individual Projects. Core B will provide an essential resource to P01 investigators who have not previously had access to formalized bioinformatics support. For investigators with existing bioinformatics collaborations Core B will assist in bringing uniform "best practices" to quality assessment, analysis and interpretation of RNA-Seq data while minimizing duplication of effort. This includes developing procedures and simple automated workflows to integrate existing specialized tools to provide a unified framework for storage, comparison, analysis and visualization of these data sets. Interaction with Sage Bionetworks will be particularly valuable, exploiting their tools for integration and visualization of diverse biological data, and their ongoing effort to standardize and distribute all publicly available microarray and sequencing data. This work required developing automated workflows that reliably processed 15,000 distinct microarray data sets, yielding standardized information in a usable format for the community. Similar work is underway for RNASeq data. These workflows will serve as a template for the proposed analyses. Additionally, Dr. Ruzzo's experience with next-generation sequence technologies (both RNA-Seq and ChlP-Seq analyses) and expertise in prediction of conserved noncoding RNAs offers the prospect of identifying important, novel players in the unique biological systems addressed by this POI.

Public Health Relevance

Sophisticated computational approaches are required to optimally analyze results from next generation sequencing technologies, and this Core provides these capabilities. By extending our analyses into noncoding regions of the genome and into appropriately curated publicly available datasets we can maximize return on investment.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-OBT-A (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
United States
Zip Code
Ware, Carol B; Nelson, Angelique M; Mecham, Brigham et al. (2014) Derivation of naive human embryonic stem cells. Proc Natl Acad Sci U S A 111:4484-9
Murry, Charles E; Chong, James J H; Laflamme, Michael A (2014) Letter by Murry et al regarding article, "Embryonic stem cell-derived cardiac myocytes are not ready for human trials". Circ Res 115:e28-9
Tung, Jason C; Paige, Sharon L; Ratner, Buddy D et al. (2014) Engineered biomaterials control differentiation and proliferation of human-embryonic-stem-cell-derived cardiomyocytes via timed Notch activation. Stem Cell Reports 2:271-81
Yang, Xiulan; Rodriguez, Marita; Pabon, Lil et al. (2014) Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J Mol Cell Cardiol 72:296-304
Naumova, Anna V; Modo, Michel; Moore, Anna et al. (2014) Clinical imaging in regenerative medicine. Nat Biotechnol 32:804-18
Guan, Xuan; Mack, David L; Moreno, Claudia M et al. (2014) Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery. Stem Cell Res 12:467-80
Mathieu, Julie; Zhou, Wenyu; Xing, Yalan et al. (2014) Hypoxia-inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. Cell Stem Cell 14:592-605
Nguyen-Tran, Diem-Hang; Hait, Nitai C; Sperber, Henrik et al. (2014) Molecular mechanism of sphingosine-1-phosphate action in Duchenne muscular dystrophy. Dis Model Mech 7:41-54
Chong, James J H; Yang, Xiulan; Don, Creighton W et al. (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510:273-7
Jiao, Alex; Trosper, Nicole E; Yang, Hee Seok et al. (2014) Thermoresponsive nanofabricated substratum for the engineering of three-dimensional tissues with layer-by-layer architectural control. ACS Nano 8:4430-9

Showing the most recent 10 out of 57 publications