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Overview of Project 1

Data and Methodology

Education

Coming:

  • Analyzed Microarray Data for IGF dataset
  • Analyzed Microarray Data for Embryo dataset

Overview of Project 1:

Our goal is to build a global picture of the transcriptional regulatory network during cardiac hypertrophy and failure. Candidate genes that are identified in this study will then undergo SNP analysis by the Whitehead Genome Center in the Framingham Heart Study population (see Project 5).

This PGA is designed to generate a well characterized "benchmark" data set for each mouse model, consisting of gene expression profiles, histological characterization, and physiological data. The data generated by all of the above studies will be analyzed using state-of-the-art tools of informatics, extensively annotated and made freely available to the research community through an interactive website.

We hope that these resources together with your research will lead to new hypotheses, a better understanding of the disease process, and ultimately the identification of novel therapeutic targets in the prevention and treatment of human heart failure.

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Participants

Position

Seigo Izumo Principal Investigator
Martina Schinke Co-Investigator
Patrick Jay MD PhD Co-Investigator
Julie McMullen Co-Investigator
Oleg Tarnavski Collaborator
John Aach Collaborator
Roderick Bronson Consultant
George Church Co-Investigator
Tetsuo Shioi Co-Investigator
Atul Butte Co-Investigator
Thomas Hampton Co-Investigator
Ary Goldberger Co-Investigator
Isaac Kohane Co-Investigator
Lauren Riggi Research Technician
Jeffrey Brown Research Technician
Joshua LaBaer Co-Investigator
Deborah Burstein Co-Investigator
Sek Won Kong Bioinformatician
Qing Nie Research Technician
Hua Wang Programmer
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Project Publications

Abstracts

Tissue expression profiling in human pressure overload hypertrophy due to aortic stenosis.
Different Transcriptional Profiles in Physiological and Pathophysiological Cardiac Hypertrophy
Microarray-Based Analysis of Gene Expression During Pressure-Overload Induced Cardiac Hypertrophy
Gene Expression During Cardiac Remodeling
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Analysis Techniques

Aligning gene expression time series with time warping algorithms
An Open-source Oligonucleotide Microarray Probe Standard for Human and Mouse.
Computation-based discovery of related transcriptional regulatory modules and motifs from a combinatorial model.
Computational comparison of two draft sequences of the human genome
Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks
Method for Non-invasively Recording Electrocardiograms in Conscious Mice
Analysis of matched mRNA measurements from two different microarray technologies.
Comparing expression profiles of genes with similar promoter regions.
The use and analysis of microarray data.
Analysis of the DNA-binding affinity, sequence specificity and context dependence of the glucocorticoid receptor zinc finger region.
Analysis of genomic and proteomic data using advanced literature mining.
Mining the literature and large datasets.
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Books

Large-scale expression profiling in cardiovascular disease using microarrays: prospects and pitfalls
Microarrays for an Integrative Genomics
Relevance Networks: A First Step Towards Finding Genetic Regulatory networks Within Microarray Data
Analysis of Protein - DNA Interactions
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Cardiac Matters

Akt/protein kinase B promotes organ growth in transgenic mice
Cardiac transgenic and gene-targeted mice as models of mouse hypertrophy and failure: A problem of (new) riches.
Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx 2.5.
The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development.
The conserved phosphoinositide 3-kinase pathway determines heart size in mice.
Vertebrate homologs of tinman and bagpipe: roles of the homeobox genes in cardiovascular development.
The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase (p110 alpha) pathway
Phosphoinositide 3-kinase(p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy
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Cell Cycles

Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression.
Stimulation of the antigen receptor on WEHI-231 B lymphoma cells results in a voltage-independent increase in cytoplasmic calcium.
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Data Integration

PGAGENE: integrating quantitative gene-specific results from the NHLBI Programs for Genomic Applications
Challenges in bioinformatics: infrastructure, models and analytics.
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Gene Expression

Reproducibility of gene expression across generations of Affymetrix microarrays
Mouse Cardiac Surgery: Comprehensive Techniques for the Generation of Mouse Models of Human Diseases and Their Application for Genomic Studies.
Determining significant fold differences in gene expression analysis.
Extracting knowledge from dynamics in gene expression.
Comparing the similarity of time-series gene expression using signal processing metrics.
Reproducibility of gene expression across generations of Affymetrix microarrays.
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Non-Cardiogenomics Investigators Utilizing Our Resources

MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data
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Physiology

Enhanced gene expression of Na(+)/Ca(2+) exchanger attenuates ischemic and hypoxic contractile dysfunction.
Intracellular calcium dynamics in mouse model of myocardial stunning
What is physiologic complexity and how does it change with aging and disease?
Fractal dynamics in physiology: alterations with disease and aging.
Further defining housekeeping, or "maintenance" genes: focus on a compendium of gene expression in normal human tissues.
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Proteomics

FLEXGene repository: from sequenced genomes to gene repositories for high-throughput functional biology and proteomics.
Rapid Sequencing of Miniprep DNA Using Sequenase and End-Labeled Sequencing Primer
Proteome-scale purification of human proteins from bacteria.
The FLEXGene repository: exploiting the fruits of the genome projects by creating a needed resource to face the challenges of the post-genomic era.
Genomics, proteomics, and the new paradigm in biomedical research.
High throughput protein production for functional proteomics.
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