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CBB
Overview
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DCODE.org
Dcode.org Comparative Genomics Center

Group Members
Leelavati Narlikar
Leila Taher
Valer Gotea


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Ivan Ovcharenko's Research Group
  Research Projects Collaborations Resources Publications

Contact Information:

  Ivan Ovcharenko, Ph.D.

Investigator
Computational Biology Branch
National Center for Biotechnology Information (NCBI)
NLM, NIH, Building 38A, Room 6S602
8600 Rockville Pike, Bethesda, MD 20894

Phone: (301) 435-8944
Fax: (301) 480-2290
Email: ovcharei_AT_ncbi.nlm.nih.gov

Research Interests:

  • Comparative genomics and evolution
  • Semantics of the gene regulatory code
  • Disease-causing noncoding mutations
  • Integration of computational biology and experimentation
  • Heart and brain gene regulatory networks



Open postdoctoral position.


Translational Research: From Sequence to Function, to Disease.


  The research of the Ovcharenko group focuses on deciphering semantics and studying evolution of the gene regulatory code in eukaryotes.

With less than 2% of the human genome sequence being coding, the search for noncoding functional DNA is a guileless treasure hunt. We currently lack fundamental understanding of the genomic language that governs the temporal and spatial dynamics of gene expression regulation, native to every cell of a living creature. In an effort to breach the gap between the modern success in genome sequencing and sequencing data interpretation, we are developing pattern recognition methods to functionally characterize noncoding DNA. Our ultimate goal is to be able to use these methods in translating noncoding genome sequence into function.

Understanding the gene regulatory landscape of the human genome will open doors for studies of population variation in noncoding functional elements, thus promoting identification of disease-causing mutations residing outside of genes. Although one of the common hypotheses speculates that mutations in gene regulatory regions might be mainly linked to an increased susceptibility to disease, not necessarily resulting in disease, our research has a potential for mapping key regulatory elements in the vicinity of disease-linked genes. Availability of computationally defined datasets of human regulatory elements tailored to specific common diseases (including heart disease, obesity, diabetes, and cancer, for example) will permit designing novel disease susceptibility measurement methods, expressly targeting selected elements.

We utilize comparative genomics, Bayesian statistics, multiple sequence alignments, libraries of transcription factor binding sites, microarray gene expression data, sequence pattern recognition techniques, dynamic programming, population genetics, and transgenic animals experimentation (the latter through collaborations); all to infer the noncoding genome function through the analysis of sequence data and evolutionary trends. As part of our trust in interdisciplinary research, we treasure and aspire to expand our collaborative studies with several research and clinical groups within the NIH and from other research Universities and Institutions.


Collaborative Projects:


  Dr. Len Pennacchio
Lawrence Berkeley National Laboratory
Forebrain gene regulation. Computational analysis of sequence motifs specific to forebrain enhancers. Transgenic mouse experimentation.
  Dr. Gabriela Loots
Lawrence Livermore National Laboratory
Bone development. Identification of bone development genes and gene regulatory elements. Characterization of limb, cartilage, and bone enhancer elements in transgenic frog, Xenopus tropicalis.
  Prof. John Rubenstein
University of California, San Francisco
Forebrain development. Reconstruction of forebrain gene regulatory networks. Identification of upstream regulators responsible for the initiation of regulatory cascades in different sub-domains of the forebrain.
  Dr. David Klein
NICHD, NIH
Pineal gland development. Using microarray data to identify enhancer elements and key transcription factors playing role in the pineal gland development.
  Prof. Marcelo Nobrega
University of Chicago
Heart regulatory code. Coupled computational identification and experimental validation of gene regulatory elements partaking in the heart development. Transgenic zebrafish experimentation.
  Dr. Laura Elnitski
NHGRI, NIH
Gene expression repressors. Identification of regulatory elements with repressor function in the human genome. Experimental validation of predicted liver repressors in Hep G2 cell lines.
  Prof. Webb Miller
Penn State University
Genome evolution. Development of software resources for evolutionary studies. Comparative genomics analysis of variable gene desert evolution in eukaryotic genomes.
  Dr. John Spouge
NCBI, NIH
Sequence pattern analysis. Development of computational methods to identify specific sequence patterns in gene regulatory elements with shared biological functions.

Additional Resources:


  DCODE.org Dcode.org Comparative Genomics Center
  ECR Browser Interactive browser of genome conservation and evolution
  SynoR Genome scanner for gene regulatory elements with synonymous function
  Mulan Multiple sequence alignment tool (TBA-based)
  zPicture Pairwise sequence alignment tool (blastz-based)
  eShadow Phylogenetic shadowing
  MultiTF Identification of transcription factor binding sites (TFBS) conserved in multiple alignments
  rVista 2.0 Identification of TFBS conserved in pairwise alignments
  Creme 2.0 Cis-REgulatory Module Explorer
  Array2BIO Integrative platform for the analysis of microarray data
  ECRbase Database of evolutionary conserved regions (ECRs), promoters, and TFBS in vertebrate genomes

Selected Publications:


  L.A. Pennacchio, G.G. Loots, M.A. Nobrega, and I. Ovcharenko, Predicting tissue-specific enhancers in the human genome, Genome Research, 17(2), 201-11 (2007) [PDF].

I. Ovcharenko and M.A. Nobrega, Identifying synonymous regulatory elements in vertebrate genomes, Nucleic Acids Research, 33, W403-7, (2005) [PDF].

G.G. Loots and I. Ovcharenko, Dcode.org anthology of comparative genomic tools, Nucleic Acids Research, 33, W56-64, (2005) [PDF].

I. Ovcharenko, G.G. Loots, M.A. Nobrega, R.C. Hardison, W. Miller, and L. Stubbs, Evolution and functional classification of vertebrate gene deserts, Genome Research, 15, 137-145 (2005) [PDF]

International Chicken Genome Sequencing Consortium, Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution, Nature, 432, 695-716 (2004)

I. Ovcharenko, L. Stubbs, and G.G. Loots, Interpreting mammalian evolution using Fugu genome comparisons, Genomics, 84(5), 890-895 (2004) [PDF]

M. Nobrega*, I. Ovcharenko*, V. Afzal, E. Rubin, Scanning Human Gene Deserts for Long-Range Enhancers, Science 302(5644), 413 (2003) [PDF]

D. Boffelli, J. MacAuliffe, D. Ovcharenko, K. Lewis, I. Ovcharenko, L. Pachter, E. Rubin, Phylogenetic analysis of primate sequences reveals functional regions of the human genome, Science, 299(5611), 1391-4, (2003) [PDF]

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Last modified: January 31, 2008