Institute Publications: 2008 / 2007 / 2006 / 2005 / 2004 / 2003 / 2002

As biology explores more complex phenomena and biological data becomes more quantitative, the need for mathematical and computational approaches to organize this information and provide predictive models becomes more acute. BioMaPS Institute faculty are deeply engaged in this effort. The unifying concept is the study of new phenomena emerging out of the interactions among many components studied on different length and time scales. There are three major research themes:

1. structural biology and biophysics of macromolecular complexes with emphasis on transcription, from the interactions of DNA with polymerase and transcription factors, up through the study of chromatin structure and the implications for gene regulation

2. the modeling of biomolecular networks at a cellular level with emphasis on how these networks control the dynamical behavior of cells

3. the development and application of bioinformatic tools for translational research in biomedicine with emphasis on cancer biology.

The following papers published by Institute faculty over the last several years provide a more detailed view of our research efforts, accomplishments, and goals.

Structural Biology of Transcription

Benoff, B., H. Yang, C. Lawson, G. Parkinson, J. Liu, E. Blatter, Y.W. Ebright, H. Berman, R.H. Ebright.
“Structural basis of transcription activation: Structure of the CAP-alpha CTD-DNA complex.” Science. 297:1562-1566 (2002)

Mekler, V., E. Kortkhonjia, J. Mukhopadhyay, J. Knight, A. Revyakin, A.N. Kapanidis, W. Niu, Y.W. Ebright, R. Levy, R.H. Ebright.

“Structural organization of bacterial RNA polymerase holoenzyme and the RNA polymerase-promoter open complex.” Cell. 108:599-614 (2002)

Napoli, A.A., C.L. Lawson, R. H. Ebright, H.M. Berman.

“Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: Recognition of pyrimidine-purine and purine-purine steps.” J Mol Biol. 357:173-183 (2006)

Swigon, D., B.D. Coleman, W.K.Olson.

“Modeling the Lac repressor-operator assembly. I. The influence of DNA looping on Lac repressor conformation.” Proc. Natl. Acad. Sci., USA. 103:9879-9884 (2006)

Tadigotla, V.R., D. O’Maoiléidigh, A.M. Sengupta, V. Epshtein, R.H. Ebright, E. Nudler, A.E. Ruckenstein.

“Thermodynamic and kinetic modeling of transcriptional pausing.” Proc Natl Acad Sci USA. 103:4439-4444 (2006)

Tolstorukov M.Y., A.V. Colasanti, D.M. McCandlish, W.K. Olson, V.B. Zhurkin.

“A novel roll-and-slide mechanism of DNA folding in chromatin: Implications for nucleosome positioning.” J Mol Biol.371:725-738 (2007)

Genomics and Systems Biology

Angeli, D., J.E. Ferrell, Jr., E.D. Sontag.

“Detection of multi-stability, bifurcations, and hysteresis in a large class of biological positive-feedback systems.” Proc. Natl. Acad. Sci. USA. 101:1822–1827 (2004)

Boczko, E.M., T.G. Cooper, T. Gedeon, K. Mischaikow, D.G. Murdock, S. Pratap, K.S. Wells.

“Structure theorems and the dynamics of nitrogen catabolite repression in yeast.” Proc Natl Acad Sci USA. 102:5647-5652 (2005)

Boczko E, T. Gedeon, K. Mischaikow.

“Dynamics of a simple regulatory switch.” J Math Biol. 55:679- 719 (2007)

Morozov, A., E. Siggia.

“Connecting protein structure with predictions of regulatory sites.” Proc. Natl. Acad. Sci. USA. 104:7068-7073 (2007)

Nagaraj, V., R. O'Flanagan, A. Bruning, J. Mathias, A. Vershon, A. Sengupta.

“Combined analysis of expression data and transcription factor binding sites in the yeast genome.” BMC Genomics. 5:59 (2004)

Roma, D.M., R.A. O'Flanagan, A.E. Ruckenstein, A.M. Sengupta, R. Mukhopadhyay.

“Optimal path to epigenetic switching.” Physical Review E. 71:011902 (2005)

Sengupta, A.M., M. Djordjevic, B.I. Shraiman.

"Specificity and robustness in transcription control networks."99:2072-2077 (2002) Proc. Natl. Acad. Sci. USA.

Bioinformatics and Translational Medicine

Alexe G., G. S. Dalgin, R. Ramaswamy, C. DeLisi, G. Bhanot,

“Data perturbation independent diagnosis and validation of breast cancer subtypes using clustering and patterns.” Cancer Informatics. 2:243–274 (2006)

Alexe, G., G. S. Dalgin, D. Scanfeld, P. Tamayo, J. P. Mesirov, C. DeLisi, L. Harris, N. Bernard, M. Martel, A. J. Levine , S. Ganesan, G. Bhanot,

“High expression of lymphocyte-associated genes in node negative HER2+ breast cancers correlates with lower recurrence rates.” Cancer Research.67:10669-10676 (2007)

Alexe, G., N. Fuku, E. Bilal, H.Ueno, Y. Nishigaki, Y. Fujita, M. Ito, Y. Arai, N. Hirose, G. Bhanot, M. Tanaka.

“Enrichment of longevity phenotype in mtDNA haplogroups D4b2b, D4a and D5 in the Japanese population.” Human Genetics. 121:347-56 (2007)

Bhanot G., G. Alexe, B. Venkataraghavan, A.J. Levine.

“A robust meta-classification strategy for cancer detection from MS data.” Proteomics. 6:592-604 (2006)

Dalgin, G.S., G. Alexe, D. Scanfeld, P. Tamayo, J.P. Mesirov, S. Ganesan, C. Delisi C, G. Bhanot.

“Portraits of breast cancer progression.” BMC Bioinformatics. 8:291 (2007)