Microarray Center for Research on the Nervous System

Summary

Principal Investigator: Dietrich Stephan
Abstract: The Microarray Center of the Research Center of Genetic Medicine, Children?s National Medical Center, Washington DC offers the attached proposal, wherein an outline of a NINDS/NIMH Microarray Center (MC) for expression profiling is described. Assistance with experimental design, data generation, and data interpretation will be provided. It is important to recognize that the Children?s Microarray Center already fulfills such functions for NHLBI, NEI, and many other investigators, and, indeed, has well-established experimental protocols, web sites, and innovative bioinformatics methods which permit a high degree of throughput at relatively low cost (due to cost sharing with other grants and programs). Briefly, the MC is unique because we have built an expression profiling Center and amassed significant expertise through 1) an NHLBI PGA award for large-scale expression profiling (one of only 11 nationally) and an NEI intramural contract for cDNA construction, 2) becoming a "Center of Excellence" for Affymetrix technology, 3) development of a highly integrated array web site (microarray.cnmcresearch.org) for tutorials and data dissemination, 4) development of the first web-based query algorithm of our Oracle data repository, 5) being well-versed in both cDNA and Affymetrix technology, 6) having performed over 975 Affymetrix array experiments, 7) operation of the MC as a business with resident infrastructure, 8) assisting over 50 visiting investigators with array experiments to date, and 9) having resident scientific expertise for experimental design assistance. In this offering, we propose to establish a NINDS/NIMH Microarray Center for expression profiling within the existing Children?s Microarray Center. Much of the proposed structure and function of the MC is based upon our previous experience with a similar NHLBI-funded grant. The goals for the MC include: 1) web-based protocol tutorials and submission, 2) review and revisions by an experimental protocol committee (EPC) which has extensive neuroscience experience, 3) investigator-driven charge-back mechanisms (3 levels of subsidization), 4) data generation, 5) Oracle warehousing with automated timed release to the public via web-access at our site and NCBI, 6) web queries of our data repository, 5) data analysis tutorials and assistance, and 6) development of custom Affymetrix NeuroChips using our downstream large data structure and our "Center of Excellence" status as mechanisms to develop a unique, low-cost reagent for the community. While we are adept at both spotted cDNA arrays and Affymetrix arrays, we plan to offer Affymetrix stock chips as the primary data generation platform for NINDS/NIMH investigators. This is because of the inherent transportability and the ability to database results, allowing all investigators to use the results of all other investigators. Also, the databasing and web access to kernal database structures in the Oracle/LIMS Affymetrix platform is becoming quite mature, while such databasing and web access is considerably less mature with spotted cDNA arrays. We have printed and conducted large experiments with cDNA arrays (particularly the murine BMAP set), and this platform will be available to NINDS/NIMH-funded investigators as an optional service at limited, availability, even though the majority of genes in the BMAP collection are also on the MG_U74 array (more than 74%).
Funding Period: 2002-06-01 - 2005-05-31
more information: NIH RePORT

Top Publications

  1. pmc Therapeutic targets for HIV-1 infection in the host proteome
    Winnie S Liang
    Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    Retrovirology 2:20. 2005
  2. pmc SNiPer: improved SNP genotype calling for Affymetrix 10K GeneChip microarray data
    Matthew J Huentelman
    Neurogenomics Division, The Translational Genomics Research Institute TGen, Phoenix, Arizona 85004, USA
    BMC Genomics 6:149. 2005
  3. ncbi Inhibition of HIV-1 virus replication using small soluble Tat peptides
    Emmanuel Agbottah
    Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington DC 20037, USA
    Virology 345:373-89. 2006
  4. ncbi Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency
    Elizabeth A Donarum
    Developmental Neurogenetics Research Laboratory, Barrow Neurological Institute, Phoenix, Arizona, USA
    J Inherit Metab Dis 29:143-56. 2006
  5. pmc Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies
    John V Pearson
    Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
    Am J Hum Genet 80:126-39. 2007
  6. pmc Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms
    Stacey Melquist
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Am J Hum Genet 80:769-78. 2007

Scientific Experts

  • MATTHEW HUENTELMAN
  • Winnie S Liang
  • Emmanuel Agbottah
  • John V Pearson
  • Stacey Melquist
  • Dietrich A Stephan
  • Victoria L Zismann
  • Keith D Coon
  • David W Craig
  • Szabolcs Szelinger
  • Elizabeth A Donarum
  • Jennifer Gass
  • Donald B Calne
  • Ryan J Uitti
  • Eric M Reiman
  • Frank Jessen
  • Sarah Lincoln
  • Jennifer Adamson
  • Andreas Papassotiropoulos
  • Paul Tuite
  • Ashley Cannon
  • Lawrence I Golbe
  • Jennifer A Webster
  • Magdalini Tsolaki
  • Richard J Caselli
  • Matt Baker
  • Charles Adler
  • Nils Homer
  • Sigrid B Sando
  • Thomas Beach
  • Michael L Hutton
  • Eileen H Bigio
  • Waibhav D Tembe
  • Reinhard Heun
  • Heike Kolsch
  • Irene Litvan
  • Zbigniew K Wszolek
  • Richard Crook
  • Makrina Daniilidou
  • Matthew J Farrer
  • Dennis W Dickson
  • Neill Graff-Radford
  • Rebecca F Halperin
  • Jason Corneveaux
  • Mike Hutton
  • Jan O Aasly
  • Marcel Brun
  • C Jakobs
  • O Carter Snead
  • Robert C Switzer
  • Phillip L Pearl
  • K Michael Gibson
  • Eric J Murphy
  • Henry Senephansiri
  • Kay Larkin
  • Maneesh Gupta

Detail Information

Publications6

  1. pmc Therapeutic targets for HIV-1 infection in the host proteome
    Winnie S Liang
    Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA
    Retrovirology 2:20. 2005
    ..Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle...
  2. pmc SNiPer: improved SNP genotype calling for Affymetrix 10K GeneChip microarray data
    Matthew J Huentelman
    Neurogenomics Division, The Translational Genomics Research Institute TGen, Phoenix, Arizona 85004, USA
    BMC Genomics 6:149. 2005
    ..We describe here the implementation of clustering algorithms on large training datasets resulting in improved SNP call rates on the 10K GeneChip...
  3. ncbi Inhibition of HIV-1 virus replication using small soluble Tat peptides
    Emmanuel Agbottah
    Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington DC 20037, USA
    Virology 345:373-89. 2006
    ..Finally, we show that these peptides do not allow loading of the catalytic domain of the cdk/cyclin complex onto the HIV-1 promoter in vivo...
  4. ncbi Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency
    Elizabeth A Donarum
    Developmental Neurogenetics Research Laboratory, Barrow Neurological Institute, Phoenix, Arizona, USA
    J Inherit Metab Dis 29:143-56. 2006
    ....
  5. pmc Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies
    John V Pearson
    Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
    Am J Hum Genet 80:126-39. 2007
    ....
  6. pmc Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms
    Stacey Melquist
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Am J Hum Genet 80:769-78. 2007
    ..Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease...