Ioshikhes, Ilya - University of Ottawa - Department of Biochemistry, Microbiology and Immunology

研究领域

Our research is focused on gene regulation. It includes several related projects and studies on chromatin, transcription factor (TF) interactions with DNA, promoter analysis and microRNAs. Specific projects include algorithms for mapping TF binding sites and cis-regulatory modules, nucleosome mapping, the study of the influence of histone variants on chromatin architecture, chromatin modeling, and the development of algorithms for mapping miRNA targets. Other areas of bioinformatics, such as the human milk metagenome, are also part of our area of interest. Our goal is the mathematical modeling of gene regulation processes on various levels, combined with position prediction of regulatory elements. The Ioshikhes lab accepts students from graduate programs in Bioinformatics, Biochemistry, Microbiology and Immunology, Mathematics and Statistics. Research Program The study of the regulation of gene expression is a fundamental problem in molecular biology. Transcriptional regulation is maintained through the interactions of various transcription factors (TFs) with the protein components of base transcriptional complexes. The DNA sequences of the promoters, enhancers and other regulatory regions of the genes contain specific binding sites for transcription factors and other components of the transcription machinery. These sites serve as a scaffold to bring various TFs into close proximity to each other to facilitate their interaction and form active DNA-protein regulation complexes. In our research, we focus on the investigation of interactions between promoters and transcription factor complexes and the discovery of gene regulatory modules in the proximal promoter sequences and long gene regulatory regions. To be properly understood, promoter machinery must be studied within its chromatin context. Current and planned directions of our research in this area include the refinement of nucleosome sequence patterns in new experimental data; a comparative analysis of common nucleosomes and those with histone modifications (H2A.Z, CENP-A and others); the analysis of species-specific and tissue-specific chromatin structures; an analysis of the relationship between specific mechanisms of chromatin remodelling and alternative types of chromatin architecture; and an analysis of the interaction of nucleosomes with TFs and other regulatory elements. Our research also includes algorithm development for mapping microRNA targets, the study of the human milk metagenome and other projects.

近期论文

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Ioshikhes I.P. DNA patterns for nucleosome positioning. “Genome Analysis: Current Procedures and Applications”, 2014, Horizon Scientific Press. ISBN 978 190823 0683. Morozov VY, Ioshikhes IP. Optimized position weight matrices in prediction of novel putative binding sites for transcription factors in the Drosophila melanogaster genome. PLoS One. 2013 Aug 6;8(8):e68712. doi:10.1371/journal.pone.0068712. Print 2013. Nandi S, Blais A, Ioshikhes I. Identification of cis-regulatory modules in promoters of human genes exploiting mutual positioning of transcription factors. Nucleic Acids Res. 2013 Oct;41(19):8822-41. doi: 10.1093/nar/gkt578. Epub 2013 Aug 2. Ward TL, Hosid S, Ioshikhes I, Altosaar I. Human milk metagenome: a functional capacity analysis. BMC Microbiol. 2013 May 25;13:116. doi:10.1186/1471-2180-13-116. Ramaswamy A, Ioshikhes I. Dynamics of modeled oligonucleosomes and the role of histone variant proteins in nucleosome organization. Adv Protein Chem Struct Biol. 2013;90:119-49. doi: 10.1016/B978-0-12-410523-2.00004-3. Nandi S, Ioshikhes I. Optimizing the GATA-3 position weight matrix to improve the identification of novel binding sites. BMC Genomics. 2012 Aug 22;13:416. doi:10.1186/1471-2164-13-416. Liu Y, Nandi S, Martel A, Antoun A, Ioshikhes I, Blais A. Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor. Nucleic Acids Res. 2012 Sep 1;40(17):8227-39. Epub 2012 Jun 22. Ioshikhes I, Hosid S, Pugh BF. Variety of genomic DNA patterns for nucleosome positioning. Genome Res. 2011 Nov;21(11):1863-71. doi: 10.1101/gr.116228.110. Epub 2011 Jul 12. Kaminsky Z, Tochigi M, Jia P, Pal M, Mill J, Kwan A, Ioshikhes I, Vincent JB, Kennedy JL, Strauss J, Pai S, Wang SC, Petronis A. A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder. Mol Psychiatry. 2012 Jul;17(7):728-40. doi: 10.1038/mp.2011.64. Epub 2011 Jun 7. Mavrich TN, Ioshikhes IP, Venters BJ, Jiang C, Tomsho LP, Qi J, Schuster SC,Albert I, Pugh BF. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res. 2008 Jul;18(7):1073-83. doi:10.1101/gr.078261.108. Epub 2008 Jun 12. Mavrich TN, Jiang C, Ioshikhes IP, Li X, Venters BJ, Zanton SJ, Tomsho LP, Qi J, Glaser RL, Schuster SC, Gilmour DS, Albert I, Pugh BF. Nucleosome organization in the Drosophila genome. Nature. 2008 May 15;453(7193):358-62. doi:10.1038/nature06929. Epub 2008 Apr 13. Smiraglia DJ, Kazhiyur-Mannar R, Oakes CC, Wu YZ, Liang P, Ansari T, Su J, Rush LJ, Smith LT, Yu L, Liu C, Dai Z, Chen SS, Wang SH, Costello J, Ioshikhes I, Dawson DW, Hong JS, Teitell MA, Szafranek A, Camoriano M, Song F, Elliott R, Held W, Trasler JM, Plass C, Wenger R. Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations. BMC Genomics. 2007 Nov 30;8:446. Ramaswamy A, Ioshikhes I. Global dynamics of newly constructed oligonucleosomes of conventional and variant H2A.Z histone. BMC Struct Biol. 2007 Nov 8;7:76. Ioshikhes I, Roy S, Sen CK. Algorithms for mapping of mRNA targets for microRNA. DNA Cell Biol. 2007 Apr;26(4):265-72. Review. Ioshikhes IP, Albert I, Zanton SJ, Pugh BF. Nucleosome positions predicted through comparative genomics. Nat Genet. 2006 Oct;38(10):1210-5. Epub 2006 Sep 10. Gershenzon NI, Trifonov EN, Ioshikhes IP. The features of Drosophila core promoters revealed by statistical analysis. BMC Genomics. 2006 Jun 21;7:161. Gershenzon NI, Ioshikhes IP. Promoter classifier: software package for promoter database analysis. Appl Bioinformatics. 2005;4(3):205-9. Lee DH, Gershenzon N, Gupta M, Ioshikhes IP, Reinberg D, Lewis BA. Functional characterization of core promoter elements: the downstream core element is recognized by TAF1. Mol Cell Biol. 2005 Nov;25(21):9674-86. Erratum in: Mol Cell Biol. 2005 Dec;25(24):11192. Gershenzon NI, Stormo GD, Ioshikhes IP.Computational technique for improvement of the position-weight matrices for the DNA/protein binding sites. Nucleic Acids Res. 2005 Apr 22;33(7):2290-301. Print 2005. Ramaswamy A, Bahar I, Ioshikhes I. Structural dynamics of nucleosome core particle: comparison with nucleosomes containing histone variants. Proteins. 2005 Feb 15;58(3):683-96. Gershenzon NI, Ioshikhes IP. Synergy of human Pol II core promoter elements revealed by statistical sequence analysis. Bioinformatics. 2005 Apr 15;21(8):1295-300. Epub 2004 Nov 30. Babcock M, Pavlicek A, Spiteri E, Kashork CD, Ioshikhes I, Shaffer LG, Jurka J, Morrow BE. Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu-mediated recombination events during evolution. Genome Res. 2003 Dec;13(12):2519-32. Montgomery KT, Lee E, Miller A, Lau S, Shim C, Decker J, Chiu D, Emerling S, Sekhon M, Kim R, Lenz J, Han J, Ioshikhes I, Renault B, Marondel I, Yoon SJ, Song K, Murty VV, Scherer S, Yonescu R, Kirsch IR, Ried T, McPherson J, Gibbs R, Kucherlapati R. A high-resolution map of human chromosome 12. Nature. 2001 Feb 15;409(6822):945-6. Ioshikhes IP, Zhang MQ. Large-scale human promoter mapping using CpG islands. Nat Genet. 2000 Sep;26(1):61-3. Ioshikhes I, Trifonov EN, Zhang MQ. Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2891-5.