System Biology Analysis and Modeling of Complex "omic" Data: a Service Center Approach

<p>NON-TECHNICAL SUMMARY:<br/> Exponential growth of genomic data in livestock research in the past decade has raised significant challenges to animal molecular biologists. To address these issues, a comprehensive computational systems biology approach is needed to provide understanding of biological function that control the efficiency of animal production and susceptibility or resistance to animal disease. The long-term goal is to make systems biology computational analyses and expertise accessible to the agricultural research community in a manner that expedites the discovery of biological functions. Our central hypothesis is that an integrated computational approach that employs comprehensive mathematical and statistical models for analysis and visualization can greatly improve the understanding of the underlying mechanisms of genomic data. Therefore Texas A&M, teamed
with Seralogix, propose to implement an Animal Systems Biology Analysis and Modeling Center (ASBAMC). We have defined six key specific objectives: 1) establish a web portal for dataset input; 2) install software and database in ASBAMC; 3) implement software enhancements; 4) establish research project selection methodology and committee; 5) conduct analysis for selected biological projects; 6) Establish Outreach and Educational programs. The outcome of this proposal is to provide a functioning web access for the data input and functional and updated software and database installed at ASBAMC, establish biological project selection committee to select 20-24 merit based research projects, and conduct comprehensive analysis to discover novel biological findings. Finally, an outreach and education program will be established to train next generation agricultural researchers in this national
needed field. We can immediately process and analyze datasets that have imminent impact on understanding and formulating new hypothesis in animal infection, nutrition, reproduction, physiology, in which animal genome community urgently need. The outcome of this research will eventually have a significant impact on long-range improvement of food efficiency, animal health, food safety, subsequently the sustainability and competitive of U.S. agriculture.<p>
APPROACH: <br/>We take a unique approach by leveraging the computational system biology expertise and technologies of both academic and industry that will rapidly launch Animal Systems Biology Analysis and Modeling Center (ASBAMC). By leveraging Seralogix's technology, we can establish and begin processing ""omic"" data within six months of project kickoff and thus deliver more immediate beneficial results to the scientific community while avoiding the cost of development of new tools. The ASBAMC will establish advanced analytical and visualization tools for the processing and interpretation of ""omic"" data generated from microarray, proteomics, next generation sequencing, and other platforms. The ASBAMC will support any animal/plant species, but will focus on agriculturally important animals. Besides the traditional genomics analysis tools, the center will have tools for
the analysis and visualization of, for example, host-pathogen/toxin interactions at a systems level, including tools for pathway and network analysis, system modeling and dynamic simulation. ASBAMC databases will also include function information that can be linked to the genomic sequence features. We will support the integration of diverse and important experimental data types. These system data types focus on providing a better understanding of genetic mechanism which is essential for the realization of breakthroughs in functional genomics/proteomics discovery. The ASBAMC will become a shared resource accessible to multiple research institutes. In our model, the ASBAMC will be staffed by trained and dedicated bioinformaticians, thus providing the ASBAMC clients with a virtual interdisciplinary team, helping them extract the most out of their ""omic"" data. The center will be hosted at
the Department of Poultry Science, Texas A&M University. An ASBAMC web portal will be established to provide information to the scientific community with regard to the ASBAMC mission, program description and announcements. The portal will serve as the interface by which selected Biological Project Clients can enter experimental parameters and other meta data and easily upload ""omic"" datasets to a secure ftp site and for accessing analysis and modeling results. The staffing will be provided by both Texas A&M and Seralogix, providing the center with a mixed industry/academic team to promote the training of graduate and post-doctoral associates in the field of computational systems biology. We intend to seek collaborations in which our services are included in future research proposals and to make our services available to industry.</p><p>
PROGRESS: <br/>2012/02 TO 2014/01 <br/>Target Audience: Poultry scientific community, poultry industry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Graduate students, undergraduate students, and postdoctoral scholar have training in bioinformatics analysis. How have the results been disseminated to communities of interest? Oral and poster presentations were given in scientific meetings, institutes, industry. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported. <br/>
PROGRESS: <br/>2012/02/01 TO 2013/01/31 <br/>OUTPUTS: The Animal Systems Biology Analysis and Modeling Service Center (ASBAMC) web portal is fully functional and available for review at http://asbamc.org. A mySQL database has been established to manage user information, reports, data management, and other functionality as required for the ASBAMC portal. The web portal includes a client login page for which biological project clients can access status of their analyses and upload data directly to the ASBAMC. There is a staff login page where ASBAMC activities and events can be posted as well as posting of documents and progress reports. A demo web page is also included to which potential clients can see a preview of the type of analysis and modeling. A fully functioning demo is available for users to actually navigate and explore an AMVIZManager web report. An improved GUI
was implemented to make the analyses process easier for new users. A Java based tool provides a GUI which supports the various computational tasks for analyzing the data and producing the results that feed into the Seralogix analysis and modeling visualization web reporting tool (AMVIZmanager). We have identified three key software enhancements required for this project and have focused primarily on next generation sequencing data processing and analysis. Parsing tools have been developed for different microarray formats, but is somewhat restricted to two channel and one channel arrays and not amenable to other platform technologies such as mass spec data which maybe provid in Excel like column formats for each biological sample and/or time course samples. A new data importation function was developed to import column based data. The enhancement helps to semi-automate the integration of
other omic data types. As reported previously, we have created additional tools for the processing and performing statistical analysis for determining differential significance of identified genes from next generation RNA sequencing data. A next generation sequencing pipeline was created for processing the raw reads from Illumina, SOLID and 454 platforms. To handle the vast amount of data, a GUI was developed in Java to management the data on a per project basis. The NGS processing tool is call the NGSManager. The tool provides an intuitive interface that guides the user through the many steps required for processing raw sequencing read data. The resulting pipeline produces a table of read counts by experimental condition which is then imported into Seralogix's systems biology computational pipeline which performs the differential analysis on the sequence count data. Seralogix's
importation tool (XManager) and the analysis tools (BioSignatureDS) have been modified to manage and process the annotated count tables from the NGS Manager. This pipeline supports comparative variant analysis and can be used to distinguish the differences between specie strains or to identify disease related genetic variants. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Due to delayed grant transfer from Texas A&M University to University of California, Davis (PD moved to UC Davis early this year) and difficulties encountered in recruiting a bioinformatician qualifying on implementing the tasks required for the proposed works, it is expected the grant may need be extended additional one to two years in order to accomplish the objectives proposed.</p>