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The Simons Center for Systems Biology Research

Research interests at The Simons Center for Systems Biology include genetics and genomics, polymorphisms and molecular aspects of evolution, signal transduction pathways and networks, stress responses and pharmacogenomics in cancer biology. Members of the group explore the linkage between theoretical and experimental biology. The group has developed algorithms that have led to the discovery of correlations and signals that are characteristic of viruses, diseases such as cancer, and traits such as embryonic development and longevity. Researchers also are investigating protein-protein interaction networks, including the prediction of protein-protein interactions from sequence analysis, and the dynamics of mRNA and protein expression in gene circuits.

Using tools from statistical mechanics and information theory, Members are addressing problems in population genetics and association studies, haplotype structure and gene selection in the p53 pathway, and uncovering epistatic interactions between single nucleotide polymorphisms related to cell apoptosis as well as developing protocols for molecular profiling of cancer; studying evolutionary genetics, and patterns of mutations correlated with longevity. They are exploring the bioinformatics of DNA and RNA sequences with applications including patterns of re-assortment in viruses, optimal RNA expression for vaccines and chromatin structure as a function of DNA sequence; and developing numerically efficient theoretical methods to describe quantum effects experimentally observed in enzymatic reactions.

The Center’s first publication from research on genetic predispositions to cancer, A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans, appeared in the journal Cell in November 2004.

A selection of other papers includes:

Yeang, C-H, Haussler, D. “Detecting Coevolution in and among Protein Domains”. PLoS Computational Biology (November 2007) 3(11):e211. 

Beg, Q.K., Vazquez, A., Ernst, J., de Menezes, M.A., Bar-Joseph, Z., Barabási, A.-L., and Oltvai, Z.N. “Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity”. PNAS (July 31, 2007) vol. 104 no. 31 (12663-12668).

Calderwood, M.A., Venkatesa, K., Xing, L., Chase, M.R., Vazquez, A., Holthaus, A.M., Ewence, A.E., Li, N., Hirozane-Kishikawa, T., Hill, D.E., Vidal, M., Kieff, E., and Johannsen, E. “Epstein-Barr virus and virus human protein interaction maps”.  PNAS (May 1, 2007) vol. 104 no. 18 (7606-7611). 

Vazquez, A., Rácz, B., Lukács, A., and Barabási, A-L. “Impact of Non-Poissonian Activity Patterms on Spreading Processes”.  Physical Review Letters (Week ending April 13, 2007) 98 (15), 158702 (1-4).

Atwal, G.S., Bond, G.L., Metsuyanim, S., Papa, M., Friedman, E., Distelman-Menachem, T., Asher, E.B., Lancet, D., Ross, D.A., Sninsky, J., White, T.J., Levine, A.J., and Yarden, R. “Haplotype structure and selection of the MDM2 oncogene in humans”. PNAS (March 13, 2007) vol. 104 no. 11 (4525-4529).

Bond, G.L., and Levine, A.J. “A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans”. Oncogene (2007) 26, 1317-1323.

Vazquex, Alexei. “Epidemic outbreaks on structured populations”. Journal of Theoretical Biology 245 (2007) 125-129.

Rabadan, R., Levine, A.J., and Robins, H.  “Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes”. Journal of Virology, (December 2006) vol. 80, no. 23 (11887-11891). 

Vazquez, Alexei.  “Spreading dynamics on heterogeneous populations: Multi-type network approach”.  Physical Review E 74 (December 21, 2006) 066114.

Vazquez, Alexei.  “Spreading dynamics on small-world networks with connectivity fluctuations and correlations”.  Physical Review E 74 (November 1, 2006) 056101.

Press, W.H. and Robins, H.  “Isochores Exhibit Evidence of Genes Interacting With the Large-Scale Genomic Environment”. Genetics (October 2006) vol. 174 (1029-1040).

Haimovich, A.D., Byrne, B., Ramaswamy, R., and Welsh, W.J.  “Wavelet Analysis of DNA Walks”. Journal of Computational Biology (Sep 2006) vol. 13 no. 7 (1289-1298).

Bond, G. L., Menin, C., Bertorelle, R., Alhorpuro, P., Aaltonen, L. A., and Levine, A. J. “MDM2 SNP309 Accelerates colorectal tumour formation in women”. Journal of Medical Genetics (published online July 6, 2006).

Bond, G.L., Hirshfield, K.M. Kirchhoff, T., Alexe, G., Bond, E.E., Robins, H., Bartel, F., Taubert, H., Wuerl, P., Hait, W., et al.  “MDM2 SNP309 Accelerates Tumor Formation in a Gender Specific and Hormonal Dependent Manner”.  Cancer Research (May 15, 2006) 66(10) (5104-10).

Alexe, G., Dalgin, G.S., Ramaswamy, R., Delisi, C., Bhanot, G. “Data Perturbation Independent Diagnosis and Validation of Breast Cancer Subtypes Using Clustering and Patterns”. Cancer Informatics, Online (2006) 2, 243-274.

Vijaya-Satya, R., Mukherjee, A., Alexe, G., Parida, L., Bhanot, G. “Constructing Near-Perfect Phylogenies with Multiple Homoplasy Events”, ISMB, Bioinformatics, (2006), 514-522.

Bhanot, G., Alexe, G., Venkataraghavan, B., Levine, A.J. “A robust meta-classification strategy for cancer detection from mass spectrometry data.”  Proteomics, (December 8, 2005) 6(2):592-604.

Robins, H., Krasnitz, M., Barak, H., Levine, A. “A Relative Entropy Algorithm for Genomic Fingerprinting Captures Host-Phage Similarities”. Journal of Bacteriology, (December 2005) vol. 187 no. 24 (8370-8374).

Harris, S., Gil, G., Robins, H., Hu, W., Hirshfield, K., Bond, E., Bond, G., Levine, A. “Detection of functional single nucleotide polymorphisms that affect apoptosis”. PNAS (November 8, 2005) vol. 102 no. 45 (16297-16302).

Robins, H., Press, W.H. “Human microRNAs target a functionally distinct population of genes with AT-rich 3’UTRs”. PNAS (October 25, 2005) vol. 102 no. 43 (15557-15562).

Alexe, G., Alexe, S., Axelrod, D.E., Hammer, P.L., and Weissmann, D. “Logical analysis of diffuse large B-cell lymphomas”. Artificial Intelligence in Medicine (July 2005) vol. 34 issue 3 (235-267).

Arva, N.C., Gopen, T.R., Talbott, K.E., Campbell, L.E., Chicas, A., White, D.E., Bond G.L., Levine, A.J., and Bargonetti, J. “A Chromatin-Associated and Transcriptionally Inactive p53-Mdm2 Complex Occurs in Mdm2 SNP309 Homozygous Cells”. Journal of Biological Chemistry (July 22, 2005) vol. 280 issue 29 (26776-26787).

Bond, G.L., Hu, W., and Levine, A. “A Single Nucleotide Polymorphism in the MDM2 Gene: From a Molecular and Cellular Explanation to Clinical Effect”.  Cancer Research (July 1, 2005) 65(13): (5481-5484) (NOTE: This is a Review).

Robins, H., Li, Y., and Padgett, R.W. “Incorporating structure to predict microRNA targets”. PNAS (March 15, 2005) vol. 102 no. 11 (4006-4009).

Ma, B., Pan, Y., Gunasekaran, K., Venkataraghavan, B., Levine, A.J., and Nussinov, R. “Comparison of the protein-protein interfaces in the p53-DNA crystal structures: Towards elucidation of the biological interface”. PNAS (March 15, 2005) vol. 102 no. 11 (3988-3993).

Ramaswamy, R. “The natural effectiveness of mathematics in the biological sciences”.Current Science (Bangalore) (10 Feb 2005) vol. 88 no. 3 (381-387).

Pan, Y., Ma, B., Venkataraghavan, B., Levine, A.J., and Nussinov, R. “In the Quest for Stable Rescuing Mutants of p53: Computational Mutagenesis of Flexible Loop L1”. Biochemistry (February 8, 2005) 44 (1423-1432).

Bhanot, G., Alexe, G., Venkataraghavan, B., Levine, A.J. A robust meta-classification strategy for cancer detection from mass spectrometry data (patent application with IBM Research and IAS, January 2005).

Alexe, G., Bhanot, G., Levine, A.J., Stolovitzky, G. “Robust diagnosis of non-Hodgkin lymphoma phenotypes validated on gene expression data from different laboratories”, Genome Informatics (2005) 16(1): 233-244.

Abramson, S., Alexe, G., Hammer, P.L., Kohn, J. “A computational approach to predicting cell growth on polymeric biomaterials”.  J Biomed Mater Res A. (2005) 73A (1):116-24.

Levine, A.J., Bargonetti, J., Bond, G.L., Hoh, J., Onel, K., Overholtzer, M., Stoffel, A., Teresky, A.K., Walsh, C.A., Jin, S. “The p53 Network”. In The p53 Tumor Suppressor. (2005) (ed.) G. Zambetti, Springer Science and Business Media, New York, pp. 1-23.

Bond, G.L., Hu, W., and Levine, A. “Mdm2 is a Central Node in the p53 Pathway: 12 Years and Counting”. Current Cancer Drug Targets (2005) (5): 3-8.

Robins, H., Alexe, G., Harris, S., Levine, A.J. “The first twenty five years of p53 research”. In : 25 Years of P53 Research, Hainaut, Pierre; Wiman, Klas (Eds.) Ch 1, 2005.

Bond, G.L., Hu, W., Bond, E.E., Robins, H., Lutzker, S., Arva, N., Bargonetti, J., Bartel, F., Taubert, H., Wuerl, P., Onel, K., Linwah, Y., Hwang, S-J., Strong, L., Lozano, G., Levine, A. “A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans”.  Cell (November 4, 2004) vol. 119 (591-602).

Plotkin, J.B., Robins, H. and Levine, A.J.. “Tissue-specific codon usage and the expression of human genes”. PNAS (August 24, 2004) vol. 101 no. 34 (12588-12591).

Alexe, G., Alexe, S., Hammer, P.L., Liotta, L., Petricoin, E., Reiss, M. “Ovarian cancer detection by logical analysis of proteomic data”. Proteomics 4 (2004) 766-783.

Bhanot, G. “Results from Modeling of B-Cell receptors binding to antigen”, Prog. Biophysics and Mol. Bio. (2004) 85, 2-3 (343-352).

Bhanot, G., Zhu, J., Louzoun, Y., and Delisi, C. “The Importance of Thermodynamic Equilibrium for High Throughput Gene Expression Arrays”, Biophysical Journal 84 (2003) 124-135.

Bhanot, G., Louzoun, Y., Weigert, M. “Dynamical Analysis of a Degenerate Primary and Secondary Humoral Immune Response”, Bulletin of Mathematical Biology 65 (2003) 535-545.