Yi (Joey) Zhou

NYU Bioinformatics Group,
715 Broadway, Rm 1012
New York, NY 10012
Phone: 212 998 3480
Fax: 212 998 3484
e-mail:joey [at] bioinformatics.nyu.edu

  • My CV can be downloaded here.
  • References and Research Statement are available upon request.

    Research Interest

    I am currently a Biology PhD student working in the NYU/Courant Bioinformatics Group. My primary research interest is in understanding the dynamics and interactions of the mechanisms behind genome evolution. My work examines evolutionary mechanisms both qualitatively and quantitatively, using methods from both computational biology and genomics. My thesis study has involved mathematical modeling, statistical methods and building novel algorithms for sequence analysis. I would like to further explore the effect of those evolution mechanisms on the organization and regulation of the molecular network in a biological system.

    Research Experience

    • Bioinformatics Group, Courant Institute & Department of Biology, NYU
      Research Assistant, August 2000~Present
    Most of the work listed below is in collaboration with Bud Mishra. I am the primary researcher on the first three projects. Additional collaborators are listed for the other projects.

    Mechanisms of segmental duplications in mammalian genomes
    To detect the mechanisms of the recent segmental duplications in mammalian genomes, we performed detailed statistical analyses on the duplication flanking regions. To further test and quantify the possible mechanisms, we developed a Markov model that incorporates the evolution dynamics of the involved genomic sequences [2]. The dynamic model enables us to avoid biases introduced by the fast-amplifying repeats, and provides us with resistance to the errors in the data. Our model suggests that the repeat recombination mechanism can explain ~10% of the duplication events. One of the repeat-independent mechanisms is related to physical instability in the DNA sequence.

    Models for the global statistical structure of genomic sequences
    To understand the effect of various evolutionary processes on the global structure of the genomic sequences, we examined the completed genomes for their generic statistical features [6]. The persistent long-range correlation and the power-law distribution of various genomic components led us to a parsimonious model of genome evolution analogous to Polya's Urn [5]. The parameters in the model fitted to real data reflect the relative rate of duplication, deletion and substitution events in each genome over its evolution history [3].

    Novel alignment-independent phylogenomic method
    Based on our genome evolution model, we developed a novel phylogenomic method based on the mer (oligonucleotides of a certain length) frequency statistics in the genomes using Maximal Likelihood method [1]. Compared to the traditional approaches, our method incorporates the number of duplications and deletions besides point mutations into the evolution distance, uses statistical information from the whole genome, and is free from the sequence alignment procedure.

    Algorithms for divergent sequence alignment (in collaboration with Salvatore Paxia and Ofer Gill)
    We have developed a randomized algorithm that can estimate the level of homology between the sequences using a Bayesian approach. After finding the regions of the desired homology levels, we use a memory efficient algorithm with an adaptive log-like gap penalty to align the sequences [4]. The ability to target sequence regions within a specific homology range and the use of the gap penalty function that reflects the biological reality makes our algorithm highly efficient for aligning divergent sequences.

    Mathematical model for cancer development (in collaboration with Matthias Heymann)
    To test the hypothesis that the development of some cancer types is based on the fixation of mutations in the stem cell pools, we developed a mathematical model for the suggested evolution process. We examined the effect of various parameters in the model on cancer progression, in accordance to real cancer records, including stem cell pool size, injury size, growth rate and division symmetry.

    Regulation and stoichiometry of the voltage-gated K+ channels (in collaboration with Todd Holmes)
    We have designed and developed recombinant tandem K+ channels in dimers, trimers, and tetramers with different combination of wild-type and mutant subunits. We examined the expression regulation of the recombinant channels by various kinases in cell culture, and further measured the activity regulation of the channels by those kinases in Xenopus oocyte by cRNA injection and voltage-clamp [7].

    • Department of Genetics, Fudan, University
      Undergraduate Thesis with Dr.Jianhua Chai, May 1997~May 1998
    Mutation analysis of human RPGR gene
    We found one of the disease-causing mutations at the 5'-end of the human RPGR cDNA by Restriction Fragment Length Polymorphism (RFLP), gene cloning and sequencing [8].


    Publications

    1.   A Novel Alignment-Independent Phylogenomic Method.
    Y. Zhou, B. Mishra.
    In preparation.

    2.   Quantifying the Mechanisms for Segmental Duplications in Mammalian Genomes by Statistical Analyses and Modeling.
    Y. Zhou, B. Mishra.
    Proc. Natl. Acad. Sci., In Press

    3.   Genome Evolution by Substitutions, Duplications and Deletions.
    Y. Zhou, B. Mishra.
    In review.

    4.   Aligning Sequences with Non-Affine Gap Penalty: PLAINS Algorithm, a Practical Implementation, and its Biological Applications in Comparative Genomics.
     O. Gill, Y. Zhou & B. Mishra.
    To appear in Proceedings of International Conference on Bioinformatics and its Applications, Fort Lauderdale, Florida, December 2004.

    5.   Models of Genome Evolution.
    Y. Zhou, B. Mishra.
    Modeling in Molecular Biology, Lecture Notes in Computer Science, Natural Computing Series, Springer, 287--304, 2004.

    6.   A Random Walk down the Genomes: DNA Evolution in Valis.
    S. Paxia, A. Rudra, Y. Zhou, B. Mishra.
    Computer, 35 (7):73--79, IEEE Press, July, 2002.

    7.   A Mechanism for Combinatorial Regulation of Electrical Activity: Ion Channel Subunits That\ Functions As SH3-Dependent Adaptor Proteins.
     M.N. Nitabach, D.A. Llamas, R.C. Araneda, J.L. Intile, I.J. Thompson, Y. Zhou, T.C. Holmes.
    Proc. Natl. Acad. Sci. 98(2):705--710, 2001.

    8.   Novel cDNA Sequences in the 5'-end of RPGR Gene.
    L. Jin, Y. Zhou, J. Chai.
    High Technology Letters (China) 9(7):39--44, 1999.


    Presentations and Abstracts

    Genome Evolution by Substitutions, Duplications and Deletions.
    Y. Zhou, B. Mishra
    Oral presentation in 22nd IUPAP International Conference on Statistical Physics, Bangalore, India, 2004.

    Statistical analyses on the flanking regions of segmental duplications in the human genome.
    Y. Zhou, S. Paxia, B. Mishra.
    CSH meeting on The Biology of Genomes, Cold Spring Harbor Lab, Long Island, May, 2004.

    Modeling and Simulating Genome Evolution by Duplication.
    Y. Zhou, S. Paxia, A. Rudra, B. Mishra.
    CSH meeting on Genome Informatics, Cold Spring Harbor Lab, Long Island, May, 2003.

    Detecting and Modeling Long Range Correlation in Genomic Sequences.
    Y. Zhou, A. Rudra, S. Paxia, B. Mishra.
    International Conference on Complex Systems (ICCS2002), Nashua, NH, June 9-14, 2002.

    Genome Evolution Models, Gene Grammar and VALIS Genome Analysis Tool
    Y. Zhou, A. Rudra, S. Paxia and B. Mishra.
    15th annual meeting on Genome Sequencing & Biology, Cold Spring Harbor Lab, Long Island, May 2002.

    Protein Tyrosine Kinases and Lipid Kinases Associate Directly with Kv1.4 Potassium Channel Subunits via Phophotyrosine-dependent SH2 Domain Interactions.
    Y. Zhou, M. N. Nitabach, C.S. Reiss, T.C. Holmes.
    Society for Neuroscience Abstracts, 26(2):1636, 2000.