Ilya Shmulevich, PhD

Professor

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shmulevich

Ilya Shmulevich received his Ph.D. in Electrical and Computer Engineering from Purdue University, West Lafayette, IN, in 1997. His graduate research was in the area of nonlinear signal processing, with a focus on the theory and design of nonlinear digital filters, Boolean algebra, lattice theory, and applications to music pattern recognition. From 1997-1998, he was a postdoctoral researcher at the Nijmegen Institute for Cognition and Information at the University of Nijmegen and National Research Institute for Mathematics and Computer Science at the University of Amsterdam in The Netherlands, where he studied computational models of music perception and recognition, focusing on tonality induction and rhythm complexity. In 1998-2000, he worked as a senior researcher at the Tampere International Center for Signal Processing at the Signal Processing Laboratory in Tampere University of Technology, Tampere, Finland. While in Tampere, he did research in nonlinear systems, image recognition and classification, image correspondence, computational learning theory, multiscale and spectral methods, and statistical signal processing.

This background proved to be fruitful for undertaking problems in computational biology at a time when genomic technologies were beginning to produce large amounts of data. In 2001, he joined the Department of Pathology at The University of Texas M. D. Anderson Cancer Center as an Assistant Professor and held an adjunct faculty appointment in the Department of Statistics in Rice University. His work in cancer genomics research spans multiple cancers, with published work in glioma, lymphoma, leukemia, breast cancer, ovarian cancer, and sarcoma. He and his colleagues developed statistical approaches for cancer classification, diagnosis, and prognosis, and applied them to the study of of metastasis, cancer progression, and tumor heterogeneity. Together with long-standing collaborators Edward R. Dougherty (Texas A&M University) and Wei Zhang (M.D. Anderson Cancer Center), he co-developed the model class of probabilistic Boolean networks (PBNs), which was applied to the study of gene regulatory networks in cancer.

Dr. Shmulevich joined the ISB faculty in 2005 where he is currently a Professor. He directs a Genome Data Analysis Center as part of The Cancer Genome Atlas (TCGA) project, a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. He also directs the Computational Core of the Systems Approach to Immunity and Inflammation consortium, which consists of a large multidisciplinary team of investigators working in the fields of immunology and systems biology. These projects entail the development of computational and mathematical approaches for modeling biological systems and analyzing large-scale measurement data sets. Dr. Shmulevich’s research interests also include theoretical studies of complex systems, including information theoretic approaches, as well as the application of image processing and analysis to high-throughput cellular imaging.

Dr. Shmulevich is a co-editor or co-author of six books in the areas of computational biology. He holds Affiliate Professor appointments in the Departments of Bioengineering and Electrical Engineering at the University of Washington, Department of Signal Processing in Tampere University of Technology, Finland, and Department of Electronic and Electrical Engineering in Strathclyde University, Glasgow, UK.

Computational biology, signal and image processing

PhD, Electrical and Computer Engineering Purdue University, 1997

2015

Turner K.M, Sun Y, Ji P, Granberg K.J, Bernard B, Hu L, Cogdell D.E, Zhou X.,Yli-Harja O, Nykter M et al..  2015.  Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression. Proceedings of the National Academy of Sciences of the United States of America. 112:3421-6.

Glusman G, Severson A., Dhankani V., Robinson M, Farrah T, Mauldin DE,Stittrich A.B, Ament SA, Roach JC, Brunkow M.E et al..  2015.  Identification of copy number variants in whole-genome data using Reference Coverage Profiles. Frontiers in genetics. 6:45.

2014

Kemp CJ, Moore J.M, Moser R., Bernard B, Teater M., Smith L.E, Rabaia N.A,Gurley K.E, Guinney J., Busch S.E et al..  2014.  CTCF Haploinsufficiency Destabilizes DNA Methylation and Predisposes to Cancer. Cell reports.

Liu G, Sun Y, Ji P, Li X, Cogdell D, Yang D, Kerrigan B.CParker, Shmulevich I,Chen K, Sood AK et al..  2014.  MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer. The Journal of pathology. 233:308-18.

Ruusuvuori P, Lin J, Scott A.C, Tan Z., Sorsa S., Kallio A., Nykter M, Yli-Harja O,Shmulevich I, Dudley AM.  2014.  Quantitative analysis of colony morphology in yeast.BioTechniques. 56:18-27.

Li X, Liu Y, Granberg K.J, Wang Q, Moore LM, Ji P, Gumin J., Sulman E.P, Calin G.A, Haapasalo H. et al..  2014.  Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma. Oncogene.

2013

Sadot A., Sarbu S., Kesseli J., Amir-Kroll H., Zhang W, Nykter M, Shmulevich I.  2013.  Information-theoretic analysis of the dynamics of an executable biological model.PLoS One. 8:e59303.

Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, Zhao Y, Reynolds S, Cheng H,Rupaimoole R et al..  2013.  Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer. Cancer cell. 23:186-99.

Larjo A, Shmulevich I, Lahdesmaki H.  2013.  Structure learning for bayesian networks as models of biological networks. Methods in molecular biology. 939:35-45.

Mirzaei H, Knijnenburg TA, Kim B, Robinson M, Picotti P, Carter GW, Li S,Dilworth DJ, Eng JK, Aitchison JD et al..  2013.  Systematic measurement of transcription factor-DNA interactions by targeted mass spectrometry identifies candidate gene regulatory proteins. Proceedings of the National Academy of Sciences of the United States of America. 110:3645-50.

2012

Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF,Fulton LL, Dooling DJ, Ding L, Mardis ER et al..  2012.  Comprehensive molecular portraits of human breast tumours. Nature.

Liu G, Yang D, Sun Y, Shmulevich I, Xue F, Sood AK, Zhang W.  2012.  Differing clinical impact of BRCA1 and BRCA2 mutations in serous ovarian cancer.Pharmacogenomics. 13:1523-35.

Bressler R, Lin J, Eakin A, Robinson T, Kreisberg R, Rovira H, Knijnenburg T,Boyle J, Shmulevich I.  2012.  Fastbreak: a tool for analysis and visualization of structural variations in genomic data. EURASIP journal on bioinformatics & systems biology. 2012:15.

Bernard B, Thorsson V, Rovira H, Shmulevich I.  2012.  Increasing Coverage of Transcription Factor Position Weight Matrices through Domain-level Homology. PloS one. 7:e42779.

Liu Y, Sun Y, Broaddus R, Liu J, Sood AK, Shmulevich I, Zhang W.  2012.  Integrated analysis of gene expression and tumor nuclear image profiles associated with chemotherapy response in serous ovarian carcinoma. PloS one. 7:e36383.

Dougherty ER, Shmulevich I.  2012.  On the Limitations of Biological Knowledge.Current Genomics. 13:574-587.

Moore LM, Kivinen V, Liu Y, Annala M, Cogdell D, Liu X, Liu CG, Sawaya R, Yli-Harja O, Shmulevich I et al..  2012.  Transcriptome and Small RNA Deep Sequencing Reveals Deregulation of miRNA Biogenesis in Human Glioma. The Journal of pathology.

2011

Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W.  2011.  Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA : the journal of the American Medical Association. 306:1557-65.

Knijnenburg TA, Lin J, Rovira H, Boyle J, Shmulevich I.  2011.  EPEPT: A web service for enhanced P-value estimation in permutation tests. BMC bioinformatics. 12:411.

Falconnet D, Niemisto A, Taylor RJ, Ricicova M, Galitski T, Shmulevich I, Hansen CL.  2011.  High-throughput tracking of single yeast cells in a microfluidic imaging matrix.Lab Chip. 11:466-73.

Knijnenburg TA, Roda O, Wan Y, Nolan GP, Aitchison JD, Shmulevich I.  2011.  A regression model approach to enable cell morphology correction in high-throughput flow cytometry. Molecular systems biology. 7:531.

Ratushny AV, Shmulevich I, Aitchison JD.  2011.  Trade-off between Responsiveness and Noise Suppression in Biomolecular System Responses to Environmental Cues. PLoS computational biology. 7:e1002091.

2010

Galas DJ, Nykter M, Carter GW, Price ND, Shmulevich I.  2010.  Biological Information as Set-Based Complexity. IEEE transactions on information theory. 56:667-677.

Saleem RA, Long-O’Donnell R, Dilworth DJ, Armstrong AM, Jamakhandi AP, Wan Y, Knijnenburg TA, Niemisto A, Boyle J, Rachubinski RA et al..  2010.  Genome-wide analysis of effectors of peroxisome biogenesis. PLoS OnePLoS ONE. 5

Ramsey SA, Knijnenburg TA, Kennedy KA, Zak DE, Gilchrist M, Gold ES,Johnson CD, Lampano AE, Litvak V, Navarro G et al..  2010.  Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites.Bioinformatics. 26:2071-5.

Yang D, Ylipaa A, Yang J, Hunt K, Pollock R, Trent J, Yli-Harja O, Shmulevich I,Nykter M, Zhang W.  2010.  An integrated study of aberrant gene copy number and gene expression in GIST and LMS. Technol Cancer Res Treat. 9:171-8.

Erkkila T, Lehmusvaara S, Ruusuvuori P, Visakorpi T, Shmulevich I, Lahdesmaki H.  2010.  Probabilistic analysis of gene expression measurements from heterogeneous tissues. Bioinformatics. 26:2571-7.

Burdick DB, Cavnor CC, Handcock J, Killcoyne S, Lin J, Marzolf B, Ramsey SA,Rovira H, Bressler R, Shmulevich I et al..  2010.  SEQADAPT: an adaptable system for the tracking, storage and analysis of high throughput sequencing experiments. BMC Bioinformatics. 11:377.

2009

Boyle J, Rovira H, Cavnor C, Burdick D, Killcoyne S, Shmulevich I.  2009.  Adaptable data management for systems biology investigations. BMC Bioinformatics. 10:79.

Selinummi J, Ruusuvuori P, Podolsky I, Ozinsky A, Gold E, Yli-Harja O, Aderem A, Shmulevich I.  2009.  Bright field microscopy as an alternative to whole cell fluorescence in automated analysis of macrophage images. PLoS OnePLoS ONE. 4:e7497.

Nykter M, Lahdesmaki H, Rust A, Thorsson V, Shmulevich I.  2009.  A data integration framework for prediction of transcription factor targets. Ann N Y Acad Sci. 1158:205-14.

Shmulevich I, Aitchison JD.  2009.  Deterministic and stochastic models of genetic regulatory networks. Methods Enzymol. 467:335-56.

Taylor RJ, Falconnet D, Niemisto A, Ramsey SA, Prinz S, Shmulevich I, Galitski T, Hansen CL.  2009.  Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform. Proc Natl Acad Sci U S A. 106:3758-63.

Knijnenburg TA, Wessels LF, Reinders MJ, Shmulevich I.  2009.  Fewer permutations, more accurate P-values. Bioinformatics. 25:i161-8.

Litvak V, Ramsey SA, Rust AG, Zak DE, Kennedy KA, Lampano AE, Nykter M,Shmulevich I, Aderem A.  2009.  Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals. Nat Immunol. 10:437-43.

Hu L, Hittelman W, Lu T, Ji P, Arlinghaus R, Shmulevich I, Hamilton SR, Zhang W.  2009.  NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab Invest. 89:531-48.

Huang AC, Hu L, Kauffman SA, Zhang W, Shmulevich I.  2009.  Using cell fate attractors to uncover transcriptional regulation of HL60 neutrophil differentiation. BMC Syst Biol. 3:20.

2008

Lee WW, Cui D, Czesnikiewicz-Guzik M, Vencio RZ, Shmulevich I, Aderem A,Weyand CM, Goronzy JJ.  2008.  Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling.Rejuvenation Res. 11:1001-11.

Balleza E, Alvarez-Buylla ER, Chaos A, Kauffman S, Shmulevich I, Aldana M.  2008.  Critical dynamics in genetic regulatory networks: examples from four kingdoms.PLoS OnePLoS ONE. 3:e2456.

Nykter M, Price ND, Larjo A, Aho T, Kauffman SA, Yli-Harja O, Shmulevich I.  2008.  Critical networks exhibit maximal information diversity in structure-dynamics relationships. Phys Rev Lett. 100:058702.

Nykter M, Price ND, Aldana M, Ramsey SA, Kauffman SA, Hood LE, Yli-Harja O,Shmulevich I.  2008.  Gene expression dynamics in the macrophage exhibit criticality.Proc Natl Acad Sci U S A. 105:1897-900.

Liu W, Lahdesmaki H, Dougherty ER, Shmulevich I.  2008.  Inference of Boolean networks using sensitivity regularization. EURASIP J Bioinform Syst Biol. :780541.

Korb M, Rust AG, Thorsson V, Battail C, Li B, Hwang D, Kennedy KA, Roach J,Rosenberger CM, Gilchrist M et al..  2008.  The Innate Immune Database (IIDB).BMC Immunol. 9:7.

Lähdesmäki H, Shmulevich I.  2008.  Learning the structure of dynamic Bayesian networks from time series and steady state measurements. Machine Learning. 71:185-217.

Lahdesmaki H, Rust AG, Shmulevich I.  2008.  Probabilistic inference of transcription factor binding from multiple data sources. PLoS OnePLoS ONE. 3:e1820.

Kauffman S, Logan RK, Este R, Goebel R, Hobill D, Shmulevich I.  2008.  Propagating organization: an enquiry. Biology and Philosophy. 23:27-45.

Boyle J, Cavnor C, Killcoyne S, Shmulevich I.  2008.  Systems biology driven software design for the research enterprise. BMC Bioinformatics. 9:295.

Aderem A, Shmulevich I.  2008.  Taming data. Cell Host Microbe. 4:312-3.

Ramsey SA, Klemm SL, Zak DE, Kennedy KA, Thorsson V, Li B, Gilchrist M, Gold ES, Johnson CD, Litvak V et al..  2008.  Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics. PLoS Comput Biol. 4:e1000021.

2007

Krawitz P, Shmulevich I.  2007.  Basin entropy in Boolean network ensembles. Phys Rev Lett. 98:158701.

Price ND, Shmulevich I.  2007.  Biochemical and statistical network models for systems biology. Curr Opin Biotechnol. 18:365-70.

Krawitz P, Shmulevich I.  2007.  Entropy of complex relevant components of Boolean networks. Phys Rev E Stat Nonlin Soft Matter Phys. 76:036115.

Price ND, Trent J, El-Naggar AK, Cogdell D, Taylor E, Hunt KK, Pollock RE, Hood L, Shmulevich I, Zhang W.  2007.  Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas. Proc Natl Acad Sci U S A. 104:3414-9.

Niemisto A, Korpelainen T, Saleem R, Yli-Harja O, Aitchison JD, Shmulevich I.  2007.  A K-means segmentation method for finding 2-D object areas based on 3-D image stacks obtained by confocal microscopy. Conf Proc IEEE Eng Med Biol Soc. 2007:5559-62.

Vencio RZ, Shmulevich I.  2007.  ProbCD: enrichment analysis accounting for categorization uncertainty. BMC Bioinformatics. 8:383.

Ahdesmaki M, Lahdesmaki H, Gracey A, Shmulevich I, Yli-Harja O.  2007.  Robust regression for periodicity detection in non-uniformly sampled time-course gene expression data. BMC Bioinformatics. 8:233.

Vencio RZ, Varuzza L, de PBCA, Brentani H, Shmulevich I.  2007.  Simcluster: clustering enumeration gene expression data on the simplex space. BMC Bioinformatics. 8:246.

2006

Niemisto A, Selinummi J, Saleem R, Shmulevich I, Aitchison JD, Yli-Harja O.  2006.  Extraction of the number of peroxisomes in yeast cells by automated image analysis. Conf Proc IEEE Eng Med Biol Soc. 1:2353-6.

Jiang R, Mircean C, Shmulevich I, Cogdell D, Jia Y, Tabus I, Aldape K, Sawaya R, Bruner JM, Fuller GN et al..  2006.  Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays. Proteomics. 6:2964-71.

Lahdesmaki H, Hautaniemi S, Shmulevich I, Yli-Harja O.  2006.  Relationships between probabilistic Boolean networks and dynamic Bayesian networks as models of gene regulatory networks. Signal Processing. 86:814-834.

Nykter M, Hunt KK, Pollock RE, El-Naggar AK, Taylor E, Shmulevich I, Yli-Harja O, Zhang W.  2006.  Unsupervised analysis uncovers changes in histopathologic diagnosis in supervised genomic studies. Technol Cancer Res Treat. 5:177-82.

2005

Niemisto A, Dunmire V, Yli-Harja O, Zhang W, Shmulevich I.  2005.  Analysis of angiogenesis using in vitro experiments and stochastic growth models. Phys Rev E Stat Nonlin Soft Matter Phys. 72:062902.

Niemisto A, Shmulevich I, Yli-Harja O, Chirieac LR, Hamilton SR.  2005.  Automated quantification of lymph node size and number in surgical specimens of stage II colorectal cancer. Conf Proc IEEE Eng Med Biol Soc. 6:6313-6.

Shmulevich I, Kauffman SA, Aldana M.  2005.  Eukaryotic cells are dynamically ordered or critical but not chaotic. Proc Natl Acad Sci U S A. 102:13439-44.

Toulouse T, Ao P, Shmulevich I, Kauffman S.  2005.  Noise in a Small Genetic Circuit that Undergoes Bifurcation. Complexity. 11:45-51.

Gershenson C, Kauffman SA, Shmulevich I.  2005.  The role of redundancy in the robustness of random Boolean networks. Arxiv preprint nlin/0511018.

Brun M, Dougherty ER, Shmulevich I.  2005.  Steady-state probabilities for attractors in probabilistic Boolean networks. Signal Processing. 85:1993-2013.