Modeling Host Responses to Understand Severe Human Virus Infections
EMSL Project ID
48199
Abstract
This comprehensive and highly integrated systems biology program seeks to delineate the complex host responses that determine the outcome of infections with potentially lethal viruses. To achieve this goal, cells and mice will be infected with wild-type and mutant influenza A, Ebola, and West Nile viruses to collect a variety of sample sets (these activities will be carried out by two Research Projects for influenza and Ebola or West Nile virus, respectively). These research projects will be led by Dr. Yoshihiro Kawaoka at the University of Wisconsin-Madison and Dr. Michael Diamond at Washington University-St. Louis. A Technical Core led by Dr. Richard Smith (Pacific Northwest National Lab; PNNL) will utilize EMSL’s mass spectrometry resources to perform proteomics, lipidomics, and metabolomics profiling, whereas mRNA and miRNA profiling will be out-sourced on a fee-for service basis. In addition, multiple biological datasets, including virological data and data on protein-protein interactions, will be generated. All data will be analyzed by a Computational Modeling Core led by Dr. Katrina Waters (PNNL), which will integrate the diverse datasets and build predictive mechanistic and network models, including virtual lung and liver models. Based on these analyses, the two Research Projects will carry out comprehensive validation studies in vitro and in vivo (i.e., in knock-out mice). OMICs studies (as described above) from virus-infected knock-out and matched wild-type mice will be used for a second round of analysis, thereby achieving the systems biology paradigm of iterative sampling, modeling, and validation. Storage, management, and exchange of the large and diverse datasets, and outreach to the community, will be facilitated by a Data Management and Resources Dissemination Core led by Dr. Miron Livny at UW-Madison, whereas an Administrative Core led by Dr. Kawaoka will ensure that all administrative tasks are addressed. In summary, we propose a comprehensive and interactive systems biology program that will enhance predictive modeling of infectious disease and identify critical regulators of severe human virus pathogenicity that may be exploited for the development of therapeutic interventions.
Project Details
Start Date
2013-11-13
End Date
2016-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Burnum-Johnson KE, JE Kyle, AJ Eisfeld, CP Casey, KG Stratton, JF Gonzalez, F Habyarimana, NM Negretti, AC Sims, S Chauhan, LB Thackray, P Halfmann, KB Walters, YM Kim, EM Zink, CD Nicora, KK Weitz, BJM Webb-Robertson, ES Nakayasu, B Ahmer, M Konkel, VL Motin, R Baric, MS Diamond, Y Kawaoka, KM Waters, RD Smith, and TO Metz. 2017. "MPLEx: A method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling." Analyst 142(3):442-448. doi:10.1039/c6an02486f
Deng L, YM Ibrahim, ES Baker, NA Aly, AM Hamid, X Zhang, X Zheng, VBS Garimella, IK Webb, SA Prost, JA Sandoval, RV Norheim, GA Anderson, AV Tolmachev, and RD Smith. 2016. "Ion Mobility Separations of Isomers based upon Long Path Length Structures for Lossless Ion Manipulations Combined with Mass Spectrometry." ChemistrySelect 1(10):2396-2399. doi:10. 1002/slct. 201600460
Eisfeld A.J., P. Halfmann, J.P. Wendler, J.E. Kyle, K.E. Burnum-Johnson, Z. Peralta, and T. Maemura, et al. 2017. "Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis." Cell Host & Microbe 22, no. 6:817-829. PNNL-SA-120881. doi:10.1016/j.chom.2017.10.011
Kyle JE, CP Casey, KG Stratton, EM Zink, YM Kim, X Zheng, ME Monroe, KK Weitz, KJ Bloodsworth, DJ Orton, YM Ibrahim, RJ Moore, C Lee, C Pedersen, ES Orwoll, RD Smith, KE Burnum-Johnson, and EM Baker. 2017. "Comparing Identified and Statistically Significant Lipids and Metabolites in 15-Year Old Serum and Dried Blood Spot Samples for Longitudinal Studies." Rapid Communications in Mass Spectrometry 31(5):447-456. doi:10.1002/rcm.7808
Kyle J.E., K.E. Burnum-Johnson, J.P. Wendler, A.J. Eisfeld, P.J. Halfmann, T. Watanabe, and F. Sahr, et al. 2019. "Plasma lipidome reveals critical illness and recovery from human Ebola virus disease." Proceedings of the National Academy of Sciences (PNAS). 116, no. 9:3919-3928. PNNL-SA-136689. doi:10.1073/pnas.1815356116
Kyle JE, KL Crowell, CP Casey, GM Fujimoto, S Kim, SE Dautel, RD Smith, SH Payne, and TO Metz. 2017. "LIQUID: an-open source software for identifying lipids in LC-MS/MS-based lipidomics data." Bioinformatics 33(11):1744-1746. doi:10.1093/bioinformatics/btx046
Kyle JE, X Zhang, KK Weitz, ME Monroe, YM Ibrahim, RJ Moore, J Cha, X Sun, ES Lovelace, J Wagoner, S Polyak, TO Metz, SK Dey, RD Smith, KE Burnum-Johnson, and ES Baker. 2016. "Uncovering Biologically Significant Lipid Isomers with Liquid Chromatography, Ion Mobility Spectrometry and Mass Spectrometry." Analyst . doi:10.1039/C5AN02062J [In Press]
Nakayasu E S,Nicora C D,Sims A C,Burnum-Johnson K E,Kim YM ,Kyle J E,Matzke M M,Shukla A K,Chu R K,Schepmoes A A,Jacobs J M,Baric R ,Webb-Robertson BJ M,Smith R D,Metz T O 2016. "MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses" mSystems 1(3):e00043-16. 10.1128/mSystems.00043-16
Zheng X, RS Renslow, MM Makola, IK Webb, L Deng, DG Thomas, N Govind, YM Ibrahim, MM Kabanda, IA Dubery, HM Heyman, RD Smith, NE Madala, and EM Baker. 2017. "Structural Elucidation of cis/trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry." The Journal of Physical Chemistry Letters 8(7):1381-1388. doi:10.1021/acs.jpclett.6b03015
Zheng X., R. Wojcik, X. Zhang, Y.M. Ibrahim, K.E. Burnum-Johnson, D.J. Orton, and M.E. Monroe, et al. 2017. "Coupling Front-end Separations, Ion Mobility Spectrometry, and Mass Spectrometry for Enhanced Multidimensional Biological and Environmental Analyses." Annual Review of Analytical Chemistry 10. PNNL-SA-121198. doi:10.1146/annurev-anchem-061516-045212