Computational Analysis of Genome Complexity, Transcription Regulation and Cellular Phenotypes
 
 
Dr. KUZNETSOV Vladimir
Senior Principal Investigator

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Group Members
 
NameTitle
Dr. KUZNETSOV VladimirPrincipal Investigator
Dr. IVSHINA Anna V.Research Scientist
 
Research Overview

The group attempts to understand the complexities of gene and genome architecture, transcriptome regulation and their relevance for phenotypic properties of cells. The group develops and applies integrative bioinformatics, probabilistic and computational systems biology methods, which are used in the analysis of sequences and gene expression data, ranging from short regulatory macromolecules, individual genes and gene pairs, to the entire genome, gene regulatory networks and pathways.
 
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Selected Publications
 
  1. Gopinath M. Sundaram, Hisyam M. Ismail, Mohsin Bashir, Manish Muhuri, Candida Vaz, Srikanth Nama, Ghim Siong Ow, Ivshina Anna Vladimirovna, Rajkumar Ramalingam, Brian Burke, Vivek Tanavde, Vladimir Kuznetsov, E. Birgitte Lane, and Prabha Sampath.
    EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis.
    The Journal of Experimental Medicine, DOI: 10.1084/jem.20170354, Published August 21, 2017.

  2. Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V. Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun,Tuan Zea Tand, Ghim Siong Ow, Song Choon Leea, Keith Rogers, Jerrold M. Ward, Seiichi Mori, David J. Adams, Nancy A. Jenkins, Neal G. Copeland#, Kenneth Hon Kim Ban, Vladimir A. Kuznetsov# and Jean Paul Thiery#. (2016)
    Transposon insertional mutagenesis screen in mice identifies novel human breast cancer susceptibility genes and signatures for stratifying breast cancer risk groups.
    PNAS USA, Doi/10.1073, 2017.
    # correspondent author

  3. Kuznetsov VA#, Tang ZQ, Ivshina AV.
    Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets.
    BMC Genomics. 2017 (Special issue: International Conference on Intelligent Biology and Medicine ,ICIBM-2016 ), in press.

  4. Jenjaroenpun P, Wongsurawat T, Sutheeworapong S and Kuznetsov VA#.
    R-loopDB: A database for R-loop forming sequences (RLFS) and R-loops.
    Nucleic Acids Res,1-7. DB Issue, 2017 Jan 4; 45(D1):D119-D127. doi: 10.1093/nar/gkw1054. Epub 2016 Nov 28.

  5. Ow Ghim Siong and Kuznetsov VA#
    Big genomics and clinical data analytics strategies for precision cancer prognosis.
    Sci Reports (Nature PG) 6: 36493; 2016 PMID:27819294.

  6. Kuznetsov VA.
    Mathematical Modelling of Avidity of Transcription Factor-DNA Binding and Data Analysis in Genome-Scale Experiments.
    In: Methods Mol Biol. Protein Networks and Pathway Analysis.(Eds. T. Tatarinova, Yu Nikolsky) Springer-Nature (in press), 2017.

  7. Ow Ghim Siong, Tang Zhiqun, Kuznetsov VA#.
    Big data and computational biology strategy for personalized prognosis.
    Oncotarget. 2016 Jun 28;7(26):40200-40220.

  8. Grinchuk O, Efthymios Motakis, Yenamandra SP, Ow GS, Jenjaroenpun P, Tang Zhiqun, A. Yarmishyn, Ivshina AV, Kuznetsov VA.
    Sense-antisense gene-pairs in breast cancer and associated pathological pathways.
    Oncotarget 2015 Oct 28. doi: 10.18632/oncotarget.6255. [Epub ahead of print]
    PMID: 26517092

  9. Aswad L, Yenamandra SP, Ow GS, Grinchuk O, Ivshina AV, Kuznetsov VA.
    Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development.
    Oncotarget. 2015 Oct 10. doi:10.18632/oncotarget.5543. [Epub ahead of print]
    PMID: 26474389

  10. Nymoen DA, Hetland Falkenthal TE, Holth A, Ow GS, Ivshina AV, Tropé CG, Kuznetsov VA, Staff AC, Davidson B.
    Expression and clinical role of chemoresponse-associated genes in ovarian serous carcinoma.
    Gynecol Oncol. 2015 Jul 29. pii: S0090-8258(15)30091-3. doi:10.1016/j.ygyno.2015.07.107.

  11. Giannakakis A, Zhang J, Jenjaroenpun P, Nama S, Zainolabidin N, Aau MY, Yarmishyn AA, Vaz C, Ivshina AV, Grinchuk OV, Voorhoeve M, Vardy LA, Sampath P, Kuznetsov VA, Kurochkin IV, Guccione E.
    Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress.
    Sci Reports. 2015 May 29;5:9737. doi: 10.1038/srep09737.
    PMID: 26024509

  12. Lim KW, Jenjaroenpun P, Low ZJ, Khong ZJ, Ng YS, Kuznetsov VA, Phan AT.
    Duplex stem-loop-containing quadruplex motifs in the human genome: a combined genomic and structural study.
    Nucleic Acids Res. 2015 May 9. pii: gkv355. [Epub ahead of print]
    PMID: 25958397

  13. Jenjaroenpun P, Wongsurawat T, Yenamandra SP, Kuznetsov VA.
    QmRLFS-finder: a model, web server and stand-alone tool for prediction and analysis of R-loop forming sequences.
    Nucleic Acids Res. 2015 Apr 16. pii: gkv344. [Epub ahead of print]
    PMID: 25883153

  14. Batagov AO, Yenamandra SP, Jenjaroenpun P, Ivshina AV, Kuznetsov VA.
    The key role of MECOM complex locus and its products in high-grade ovarian carcinoma pathogenesis and clinical outcomes.
    Cancer Research 75 (15 Supplement), 1990-1990.

  15. Ow GS, Ivshina AV, Fuentes G, Kuznetsov VA.
    CHEK2 mutation is an adverse prognostic survival factor for patients diagnosed with high-grade serous ovarian carcinoma.
    Cancer Research. 74 (19 Supplement), 3815-3815.

  16. Ow GS and Vladimir A Kuznetsov VA.
    Multiple signatures of a disease in potential biomarker space: Getting the signatures consensus and identification of novel biomarkers.
    BMC Genomics 2015, 16(Suppl 7):S2 doi:10.1186/1471-2164-16-S7-S2.

  17. Kuznetsov V, Lee HK, Maurer-stroh S, Molnar SMJ, Pongor S, Eisenhaber B, Eisenhaber F.
    How bioinformatics influences health informatics: usage of biomolecular sequences, expression profiles, and automated microscopy image analysis for clinical needs and public health.
    Omics in Clinical Practice: Genomics, Pharmacogenomics, Proteomics, and Transcriptomics in Clinical Research (Editor: Yu Liu) 25.06; 2014, CRC Press. p.203-244.

  18. Jenjaroenpun P, Chew CS, Yong TP, Choowongkomon K, Thammasorn W, Kuznetsov VA.
    The TTSMI database: a catalog of triplex target DNA sites associated with genes and regulatory elements in the human genome.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D110-6. doi: 10.1093/nar/gku970. Epub 2014 Oct 16.
    PMID: 25324314; PubMed Central PMCID: PMC4384029.

  19. Yarmishyn AA, Batagov AO, Tan JZ, Sundaram GM, Sampath P, Kuznetsov VA, Kurochkin IV.
    HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome.
    BMC Genomics. 2014;15 Suppl 9:S7. doi: 10.1186/1471-2164-15-S9-S7. Epub 2014 Dec 8.
    PMID: 25522241; PubMed Central PMCID: PMC4290621.

  20. Ow GS, Ivshina AV, Fuentes G, Kuznetsov VA.
    Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.
    Cell Cycle. 2014;13(14):2262-80. doi: 10.4161/cc.29271. Epub 2014 May 30.
    PMID: 24879340; PubMed Central PMCID: PMC4111681.

  21. Kuznetsov Vladimir.
    Gene Networks, tumor subtypes and patient prognogtic signatures associated with ovarian cancer mutations.

  22. Jenjaroenpun P, Chew CS, Yong TP, Choowongkomon K, Thammasorn W, Kuznetsov VA.
    The TTSMI database: a catalog of triplex target DNA sites associated with genes and regulatory elements in the human genome.
    Nucleic Acids Res.( 2014) Oct 16. pii: gku970. [Epub ahead of print]
    PMID: 25324314.

  23. Tan A, Low DHP, Giannakakis A, Kuznetsov V, Ferrari C, Guccione E, Bertoletti A.
    P180 UPREGULATION OF CHROMATIN MODIFYING GENES IN EXHAUSTED T CELLS FROM CHRONIC HBV PATIENTS.
    Journal of Hepatology, 2014; 60(1), S126, Elsevier.

  24. Yeo AJ, Becherel OJ, Luff JE, Cullen JK, Wongsurawat T, Jenjaroenpoon P, Vladimir A. Kuznetsov, Peter J. McKinnon PJ, Martin F. Lavin MF.
    R-Loops in Proliferating Cells but Not in the Brain: Implications for AOA2 and Other Autosomal Recessive Ataxias.
    PLoS ONE 2014, 9(3): e90219. doi:10.1371/journal.pone.0090219.

  25. Kuznetsov VA.
    Cancer biomarker discovery via integrative medicine and bioinformatics analysis of sequencing, gene expression and clinical oncology data.
    Transl Med 2013, 3:2; 2nd International Conference on Translational & Personalized Medicine. August 05-07, 2013 Holiday Inn Chicago-North Shore, IL, USA; http://dx.doi.org/10.4172/2161-1025.S1.008.

  26. Z Tang, GS Ow, JP Thiery, AV Ivshina, VA Kuznetsov.
    Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical sub-classes in high-grade serous ovarian carcinoma.
    International Journal of Cancer. Online: 3 JUL 2013 11:36AM EST | 2014 Jan 15;134(2):306-18. DOI: 10.1002/ijc.28371.

  27. Arsen O Batagov, Igor V Kurochkin.
    Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3'-untranslated regions.
    Biology Direct 2013, 8:12 doi:10.1186/1745-6150-8-12
    Published: 7 June 2013.

  28. Jenjaroenpun P, Kremenska Y, Nair VM, Kremenskoy M, Joseph B, Kurochkin IV.
    Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing.
    PeerJ. 2013 Nov 5;1:e201.
    PMID: 24255815

  29. Batagov AO, Yarmishyn AA, Jenjaroenpun P, Tan JZ, Nishida Y, Kurochkin IV.
    Role of genomic architecture in the expression dynamics of long noncoding RNAs during differentiation of human neuroblastoma cells.
    BMC Syst Biol, 2013, 7(Suppl 3):S11 doi:10.1186/1752-0509-7-S3-S11.

  30. Z Tang, GS Ow, JP Thiery, AV Ivshina, VA Kuznetsov.
    Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical sub-classes in high-grade serous ovarian carcinoma.
    International Journal of Cancer. Online: 3 JUL 2013 11:36AM EST | 2014 Jan 15;134(2):306-18. DOI: 10.1002/ijc.28371.

  31. Sameer Phalke, Slim Mzoughi, Marco Bezzi, Nancy Jennifer, Wei Chuen Mok, Diana HP Low, Aye Aye Thike, Vladimir A Kuznetsov, Puay Hoon Tan, P Mathijs Voorhoeve, Ernesto Guccione.
    p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6.
    Nucleic Acids Research. Oct 1;40(19):9534-9542. Epub 2012 Sep 16.

  32. Xin Hui Derryn Chan, Srikanth Nama, Felicia Gopal, Pamela Rizk, Srinivas Ramasamy, Gopinath Sundaram, Ghim Siong Ow, Ivshina Anna Vladimirovna, Vivek Tanavde, Johannes Haybaeck, Vladimir Kuznetsov, and Prabha Sampath.
    Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas.
    Cell Reports, doi:10.1016/j.celrep.2012.07.012.

  33. Migliori V, Muller J, Phalke S, Low D, Bezzi M, Mok WC, Sahu SK,Gunaratne J, Capasso P, Bassi C, Cecatiello V, De Marco A, Blackstock V, Kuznetsov VA, Amati B, Mapelli M, and Guccione E.
    Symmetric Dimethylation of H3 Arginine 2 is a Novel Histone Mark that Supports Euchromatin Maintenance.
    Nature Structural Biol. 2012.

  34. Toh Swee Heng, Prathipati Philip, Motakis Efthimios, Keong Kwoh Chee, Yenamandra Surya Pavan and Kuznetsov Vladimir A.
    A robust tool for discriminative analysis and feature selection in paired samples impacts the identification of the genes essential for reprogramming lung tissue to adenocarcinoma.
    BMC Genomics, 2011 1471-2164/12/S3/S24.

  35. Wongsurawat T. Jenjaroenpun P, Kwoh CK, Vladimir Kuznetsov VA.
    Quantitative Model of R-loop Forming Structures Reveals a Novel Level of RNA-DNA Interactome Complexity.
    Nucleic Acids Research, 2011, 25 November, pp.1-15. Doi:10.1093/nar/gkr1075.

  36. Batagov A, Kuznetsov VA, Kurochkin I.
    Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles.
    BMC Genomics, 2011 12(Suppl 3):S18.

  37. Bard-Chapeau EA, Jeyakani J , Kok Chung H, Muller J, Chua Belind QL, Gunaratne J, Batagov A, Jenjaroenpun P, Kuznetsov VA, Wei CL , D'Andrea RJ. D, Bourque G, Jenkins NA , Copeland NG.
    Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS in invasive tumors.
    PNAS USA, 2012; January 19, 2012, doi:10.1073/pnas.1119229109.

  38. Yenamandra SP, Darekar SD, Kashuba V, Matskova L, Klein G, Kashuba E.
    Stem cell gene expression in MRPS18-2-immortalized rat embryonic fibroblasts.
    Cell Death Dis. 2012 Jan 19;3: e357. doi: 10.1038/cddis.2011.138.

  39. Kashuba E, Yurchenko M, Yenamandra SP, Snopok B, Szekely L, Bercovich B, Ciechanover A, Klein G.
    Epstein-Barr virus-encoded EBNA-5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53.
    Int J Cancer. 2011 Feb 15;128(4):817-25. doi: 10.1002/ijc.25414.

  40. Zhiqun Tang, Lihua Zhang, Amrita K Cheema and Habtom W Ressom.
    A new method for alignment of LC-MALDI-TOF data.
    Proteome Science 2011, 9(Suppl 1):S10 doi:10.1186/1477-5956-9-S1-S10. Published: 14 October 2011.

  41. Winston Koh, Chen Tian Sheng, Betty Tan, Qian Yi Lee, Vladimir Kuznetsov, Lim Sai Kiang, Vivek Tanavde
    Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-y microRNA family in downstream targeting of Hepatic Nuclear Factor 4 Alpha BMC Genomics 2010, Vol. 11 (Suppl 1):S6, doi:10.1186/1471-2164-11-S1-S6

  42. Alexander A Kanapin, Nicola Mulder, Vladimir A Kutznetsov.
    Projection of gene-protein networks to the functional space of the proteome and its application to analysis of organism complexity.
    BMC Genomics 2010, Vol. 11 (Suppl 1):S6, doi:10.1186/1471-2164-11-S1-S4

  43. Vladimir A Kuznetsov, Onkar Singh, Piroon Jenjaroenpun.
    Statistics of protein-DNA binding and the total number of binding sites for a transcription factor in the mammalian genome.
    BMC Genomics 2010, Vol. 11 (Suppl 1):S6, doi:10.1186/1471-2164-11-S1-S12

  44. Vladimir A Kuznetsov, Onkar Singh, Piroon Jenjaroenpun.
    Statistics of protein-DNA binding and the total number of binding sites for a transcription factor in the mammalian genome.
    BMC Genomics 2010, Vol. 11 (Suppl 1):S6, doi:10.1186/1471-2164-11-S1-S12

  45. Oleg V. Grinchuk, Piroon Jenjaroenpun, Yuriy L. Orlov, Jiangtao Zhou and Vladimir A. Kuznetsov.
    Integrative analysis of the human cis-antisense gene pairs, miRNAs and their transcription regulation patterns.
    Nucleic Acids Res. 2009, Nov 11. [Epub ahead of print]

  46. Motakis E, Ivshina A, Kuznetsov V.
    Data-driven approach to predict survival of cancer patients.
    Engineering in Medicine and Biology Magazine, IEEE. Vol 28, Issue: 4, July-Aug 2009, Pg: 58-66, ISSN 0739-5175, doi: 10.1109/MEMB.2009.932937

  47. Piroon Jenjaroenpun, Vladimir A Kuznetsov.
    TTS Mapping : integrative WEB tool for analysis of triplex formation target DNA Sequences, G-quadruplets and non-protein coding regulatory DNA elements in the human genome.
    BMC Genomics 2009, Vol. 10 (Suppl 3) :S9, doi: 10.1186/1471-2164-10-S3-S9

  48. Vladimir Kuznetsov.
    Relative Avidity, Specificity, and Sensitivity of Transcription Factor-DNA Binding in Genome-Scale Experiments.
    Methods in Molecular Biology: Protein Networks and Pathway Analysis, 2009, Vol: 563, Pg: 15-50. doi: 10.1007/978-1-60761-175-2_2, ISBN: 978-1-60761-174-5

  49. Chua, Alvin LS, Anna V. Ivshina, and Vladimir A. Kuznetsov.
    Pareto-Gamma Statistic Reveals Global Rescaling in Transcriptomes of Low and High Aggressive Breast Cancer Phenotypes.
    Lecture Notes in Computer Science 4146 (2006): 49-59.

  50. Jones MB, Michener CM, Blanchette JO, Kuznetsov VA, Raffeld M, Serrero G, Emmert-Buck MR, Petricoin EF, Krizman DB, Liotta LA, Kohn EC.
    The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer.
    Clin Cancer Res. 2003 Jan;9(1):44-51.
    PMID: 12538450

  51. VA Kuznetsov, GD Knott, AV Ivshina.
    Artificial immune system based on syndromes-response approach: recognition of the patterns of immune response and prognosis of therapy outcome.
    1998, in: Systems, Man, and Cybernetics, 1998. 1998 IEEE International Conference on. Vol. 4, Pages 3804-3809,IEEE.

  52. VA Kuznetsov, VP Zhivoglyadov, LA Stepanova.
    Kinetic approach and estimation of the parameters of cellular interaction between the immunity system and a tumor.
    Archivum immunologiae et therapiae experimentalis (Warsz). 1993;41(1):21-31.

  53. VA Kuznetsov.
    Dynamics of Immune Processes During Tumor Growth.
    Nauka Publishing House, Moscow (1992) : 340 pages (in Russian).

  54. Alekseeva EI, Kirzhner VM, Kuznetsov VA.
    Structures and Collective Behaviour.
    Znanie Publishing House (Ser: Math. and Cybernetics.N3,1991), Moscow (1991): 48 pages (in Russian).

Patent Applications
 
  1. Batagov A, Ivshina AV, Kuznetsov VA.
    Methods for diagnosis and/or prognosis of ovarian cancer.
    Patent application BII/P/06614/00/SG. Filed on 18.11.2011.

  2. Kuznetsov, V.A. and Motakis, E.
    A method for identification, prediction and prognosis of cancer aggressiveness based on selection of synergistic survival significant gene pairs.
    Sing & US patent applications. File on March 9, 2009. Eur. Application No/Patent No. 10751103.2-1527; PCT/SWG2010000080; Filed on 10.03.2010. Published date: 12/27/2011.

  3. Motakis E, Ivshina AV, Kuznetsov VA.
    Identification of biologically and clinically essential genes and gene pairs, and methods employing the identified genes and gene pairs.
    (File FP4425). ETPL REF: GIS/P/05238/00/US; US provisional patent application 10 March, application number 61/158, 948. Eur. Application No/Patent No. 10751103.2-1527; PCT/SG2010000080, Filed on 10.03.2010. Published date: 01/05/2012.

  4. Kuznetsov VA, Ivshina AV, Miller L.
    Genetic Classification of Human Breast Cancer.
    Filed on Nov.12, 2006. Filing #: GIS/Z/01109. USA and Singapore patent applications. International Application Number PCT/SG2007/000357. Application Number:12/446195 File date: 10/19/2007; Published date: 01/27/2011.

 
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