Statistical Methods for ODE Models in AIDS Research

Document text

Principal Investigator: Hulin  Wu
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
Fiscal Year: 2019
Award: $346,500
Funding agency: National Institute of Allergy and Infectious Diseases

   
DESCRIPTION (provided by applicant): Owing to the significant cost reduction of high-throughput technologies, frequent time course genome-wide gene expression data, in addition to time course cellular level and longitudinal phenotype response data, are often collected in recent HIV/AIDS studies and other biomedical projects. However, the effective use of the high-throughput time course data at transcriptomic and proteomics levels to study dynamic responses and network features is often hindered by lacking of statistical methods to reconstruct high-dimensional dynamic models. In this renewal project, we intend to fill this gap and propose the following specific aims: 1) Develop more efficient parameter estimation methods for high-dimensional ordinary differential equation (ODE) models. Aim 1 intends to develop more efficient statistical methods to estimate high-dimensional ODE model parameters to provide a foundation for reconstructing biological networks at gene, protein and molecular levels. 2) Develop novel statistical methods and implementation procedures for high-dimensional ODE variable selection to reconstruct the dynamic networks. We combine new statistical estimation methods for ODE models and regularization-based variable selection techniques to identify ODE network edges. Statistical methodologies and theoretical justifications will be established for the proposed ODE-based network models. 3) Evaluate and validate the methodologies developed in Aims 1-2 using computer simulations and real data analysis from HIV/AIDS studies. It is important to carefully evaluate the high-dimensional ODE variable selection and parameter estimation methods developed in Aims 1-2, and perform comparisons with existing methods for practical use. In particular, it is necessary to apply the proposed methods to experimental data from HIV/AIDS studies in order to demonstrate the usefulness of the proposed methodologies to address scientific questions. 4) Develop and disseminate efficient computational algorithms and user-friendly software tools for the proposed methods to the broader research community. It is very important to develop efficient computing algorithms and share/disseminate the computational source codes to the general research community.

Terms: <AIDS><AIDS Virus><AIDS/HIV><AIDS/HIV problem><Acquired Immune Deficiency><Acquired Immune Deficiency Syndrome><Acquired Immune Deficiency Syndrome Virus><Acquired Immuno-Deficiency Syndrome><Acquired Immunodeficiency Syndrome><Acquired Immunodeficiency Syndrome Virus><Acquired Immunologic Deficiency Syndrome><Address><Algorithms><Area><Basic Research><Basic Science><Biological><Biomedical Research><Biomedical Technology><Blood><Blood Reticuloendothelial System><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><Cell Communication and Signaling><Cell Line><Cell Signaling><CellLine><Communities><Complex><Computational algorithm><Computer Models><Computer Simulation><Computer Software Tools><Computer based Simulation><Computerized Models><Data><Data Analyses><Data Analysis><Differential Algebraic Equation><Differential Equation><Disease Progression><Epidemic><Foundations><Funding Agency><Funding Source><Gene Expression><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Gene Proteins><Gene Transcription><General Viruses><Genetic><Genetic Transcription><Genomics><HAART><HIV><HIV Infections><HIV vaccine><HIV-1><HIV-I><HIV/AIDS><HIV/AIDS Vaccines><HIV/AIDS problem><HIV1><HTLV-III Infections><HTLV-III-LAV Infections><High Throughput Assay><Highly Active Antiretroviral Therapy><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Human immunodeficiency virus 1><Immune system><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Infection><Intracellular Communication and Signaling><Investigators><Investments><LAV-HTLV-III><Life><Lymphadenopathy-Associated Virus><Macaca><Macaca mulatta><Macaque><Math Models><Mathematical Model Simulation><Mathematical Models and Simulations><Messenger RNA><Metabolic Pathway><Methodology><Methods><Micro RNA><MicroRNAs><Modeling><Molecular><NIH><National Institutes of Health><Network-based><Pathogenesis><Phenotype><Procedures><Protein Gene Products><Proteins><Proteomics><RNA Expression><RNA Seq><RNA sequencing><RNAseq><Regulator Genes><Research><Research Personnel><Researchers><Rhesus><Rhesus Macaque><Rhesus Monkey><SIV><Signal Transduction><Signal Transduction Systems><Signaling><Simian Immunodeficiency Viruses><Software Framework><Software Tools><Source Code><Statistical Methods><Strains Cell Lines><Systems Biology><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Techniques><Therapeutic><Time><Transcript Expression Analyses><Transcript Expression Analysis><Transcription><Transcriptional Regulatory Elements><United States National Institutes of Health><Vaccination><Vaccines><Viral Burden><Viral Load><Viral Load result><Virus><Virus-HIV><allergic/immunologic body system><allergic/immunologic organ system><base><biological signal transduction><biological systems><computational modeling><computational models><computational simulation><computer algorithm><computer based models><computerized modeling><computerized simulation><cost><cultured cell line><data interpretation><deep sequencing><design><designing><develop a vaccine><development of a vaccine><experiment><experimental research><experimental study><gene expression analysis><gene expression assay><genome scale><genome-wide><genomewide><high dimensional data><high dimensionality><high throughput screening><high throughput technology><highly active anti-retroviral therapy><human immunodeficiency virus vaccine><immunogenicity><in silico><mRNA><mathematic model><mathematical model><mathematical modeling><metabolism measurement><metabolomics><metabonomics><miRNA><miRNAs><multidimensional data><network models><new technology><non-human primate><nonhuman primate><novel><novel technologies><pathogen><plasmid vaccine><public health relevance><regulatory gene><response><temporal measurement><temporal resolution><thymus derived lymphocyte><time measurement><time use><trans acting element><transcriptional profiling><transcriptome sequencing><transcriptomics><user friendly computer software><user friendly software><vaccine development><vaccine formulation><vector vaccine><virtual simulation>