Shirley Pepke, PhD


                                           My palindromic moment of Zen:

Wolf's pal spots laminate wet animal, stops, laps flow.

Interests:  Computational/mathematical biology and genomics, especially applied to cancer and other medical applications, machine learning and bioinspired computing, modeling and prediction in complex systems.

Curriculum Vitae

        1989    B.A. in physics with Honors from the University of Chicago
            Thesis Advisor: Professor Thomas Rosenbaum
        1995    Ph.D. in physics from the University of California at Santa Barbara
            Thesis Advisor: Professor Jean Carlson


Research Scientist, Lyrid LLC, 2012-present
     •    Research consulting and software development

Independent Research Consultant, Caltech, 2012-present
     •    Scientific consulting, data analysis, and software development for high throughput genomics

Computational Biology and Physics Research

Computational Research Scientist, California Institute of Technology, 2006-2012
      •    Genomic data integration: Applied self-organizing maps to analysis of genome-wide ChIP-seq chromatin mark data related to transcriptional networks. (Wold lab/ENCODE).
        •    Models of Calcium signal transduction in neurons:  Derived coarse-grained mathematical approximation to a complex reaction network in the post-synaptic density, implemented multiple level-of-detail ODE models of the reaction network and analyzed the results (Kennedy lab).  Developed stochastic simulations to analyze spatiotemporal dynamics of the model.
        •    Graphic interface development for simulation software: Designed and developed MDLWiz, a GUI front end to MCell3. Screenshot.(Kennedy lab).
        •    Bioinformatics for Chip-seq data for the fruit fly genome:  Computed measures of sequence conservation and motif density. Developed heuristics to improve binding site inference based upon ChIP-seq data (Stathopoulos lab).
        •    Instruction: Lectured on Mathematica for science applications for a joint biology/astronomy course.

Genome Atlantic Postdoctoral Fellow, Dalhousie University, Halifax, NS, 2003-2006. 
      •    Robust phylogenetic inference: Examined the likelihood surface for phylogenetic problems and the utility of confidence set search heuristics in improving robustness of inference. Explored the use of site pattern conflicts to identify poorly modeled sites.
        •    Protein structure energies in phylogenetics:  Analyzed site-specific substitution rates based upon structural information.
        •    Recombination: Devised algorithms for detection of recombination in amino acid sequences based upon site pattern information.

Postdoctoral Fellow, Computational Biology, Berlex Biosciences, Richmond, CA,  2001-2003.
        •    Genome-wide computation   and analysis of human DNA subsequence frequencies and biological function: Architected software to compute whole genome sequence statistics and applied exploratory data analysis to resulting annotation.

Postdoctoral Fellow, Sloan Center for Theoretical Neurobiology, University of California, San Francisco, 1995-1996.
        •    A numerical model of reinforcement learning and action choice in honeybee foraging: Simulated a model bee using reinforcement feedback to adjust the weights of a predictive neural model for the amount of nectar it will receive over some time period, given its current location and health, the perceived flower distribution, and recent past experience. Invented animated graphic display system with GUI for setting simulation parameters.
        •    Visuomotor system smooth pursuit in primates: Modeled coordination of motor behavior and visual input mathematically.

Algorithms and Software Engineering

Computer Scientist, Autonomy and Robotics Area, Caelum Research and QSS Group, NASA Ames Research Center, Moffett Field, CA, 1999-2001.
        •    Livingstone2, a model-based temporal inference system for diagnosis of engineered systems: Extended a conflict-directed best-first search algorithm for simultaneous tracking of multiple system trajectories. Ported a library (L2RTAPI) from Lisp to C++ for autonomous realtime diagnosis in a multithreaded environment.
        •    Stratospheric Observatory for Infrared Astronomy (SOFIA):  Modeled flight scheduling constraints as latitude/longitude interval pruning computations using positional astronomy techniques.
        •    Sensorimotor integration and biomorph control: Innovated the use of pulse-coupled neural oscillator networks to map sensory input to adaptive output motor behaviors in serpentine robots.

Software Engineer, GIS Division, Autodesk, San Rafael, CA, 1998-1999.
Physics Software Engineer, Radical Entertainment, San Francisco, CA, 1997-1998.
Software Engineer, The Learning Company, Fremont, CA, 1996-1997.


Graduate Research Assistant, Dept. of Physics, University of California, Santa Barbara, 1992-1995.
Teaching Assistant, Dept. of Physics, University of California, Santa Barbara, 1989-1990 ,1991-1992.


     1.     “Single-cell transcriptomes reveal a dynamic lncRNA landscape during reprogramming,Daniel H. Kim, Georgi K. Marinov, Shirley Pepke, Zakary S. Singer, Peng He, Brian Williams, Gary P. Schroth, Michael B. Elowitz and Barbara J. Wold. To appear in Cell Stem Cell.
    2.     “Integrating and mining the chromatin landscape of cell type specificity using self-organizing maps, A. Mortazavi, S. Pepke, C. Jansen, G. Marinov, J. Ernst, M. Kellis, R. Hardison, R. M. Myers, and B. Wold. Genome Res. 2013 Dec; 23(12):2136-48.
“An integrated encyclopedia of DNA elements in the human genome, The ENCODE Consortium. Nature, vol. 488 (7414), (2012).
    4.    A user’s guide to the encyclopedia of DNA elements (ENCODE), The ENCODE Consortium. PLoS Biol. Epub Apr 19 (2011).
    5.     “High resolution mapping of Twist to DNA in Drosophila embryos: Efficient functional analysis and evolutionary conservation,” A. Ozdemir, K. Fisher, S. Pepke, M. Samanta, L. Dunipace, K. McCue, L. Zeng, N. Ogawa, B. Wold, and A. Stathopolous. Genome Research 21(4):566-77 (2011).
    6.    “A Dynamic model of interactions of Ca2+, calmodulin, and catalytic subunits of Ca2+/calmodulin-dependent protein kinase II,” S. Pepke, T Kinze.r-Ursem, S. Mihalas, and M. B. Kennedy, PLoS Computational Biology, vol. 6(2), e1000675 (2010).
    7.    “Computation for ChIP-seq and RNA-seq studies,” Shirley Pepke, Barbara Wold, and Ali Mortazavi. Nature Methods Nov; 6(11 Suppl):S22-32, (2009).
    8.    “Using Confidence Set Heuristics During Topology Search Improves the Robustness of Phylogenetic Inference,” Shirley Pepke, Davin Butt, Isabelle Nadeau, Andrew J. Roger, and Christian Blouin. Journal of Molecular Evolution, vol. 64(1), p. 80 (2007).
    9.    "Dynamic Models of Earthquake Faults and Forecasting in Complex Systems," S. L. Pepke, in the 1993 Lectures in Complex Systems, eds. L. Nadel and D. L. Stein, Addison-Wesley:  Reading, MA (1995).
    10.    "Prediction Studies of Earthquake Fault Models and Applications to Seismic Catalogs," J. M. Carlson, S. L. Pepke, and V. Kossobokov, in Reduction and Predictability of Natural Disasters, eds. J. Rundle, W. Klein, and D. Turcotte, Addison-Wesley:  Reading, MA (1996).
    11.  "Predictability of Self-organizing Systems," S. L. Pepke and J. M. Carlson, Physical Review E, vol. 50, p. 236 (1994).
    12.  "Prediction of Large Events on a Dynamical Model of a Fault," S. L. Pepke, J. M. Carlson, and B. E. Shaw, Journal of Geophysical Research - Solid Earth, vol. 99, p. 6769 (1994).
    13.   "Electronic States in a Disordered Metal - Magnetotransport in Doped Germanium," T. F. Rosenbaum, S. Pepke, R. N. Bhatt, and T. V. Ramakrishnan, Physical Review B, vol. 42, p. 11214 (1990).

Published Software

    1.     “Livingstone2,” automated spacecraft diagnostic software, NASA opensource, 2002.
    2.    Autodesk World Release 2.1 (1999)
    3.    Mission Think (1996)

Selected Research Presentations

    "Clustering of genome-wide chromatin mark data using Self-Organizing Maps", Shirley Pepke, Ali Mortazavi, and Barbara Wold, Genome Informatics, Cold Spring Harbor, NY, 2011.
    "Visualization and Data Mining of Integrated Whole Genome Data Using Self-Organizing Maps", (poster) Shirley Pepke, Ali Mortazavi, Georgi Marinov, and Barbara Wold, ENCODE/modENCODE Consortium Conference, March 2010.
    Kinetic models of interactions among Ca(2+), calmodulin, and CaMKII: molecular components of learning and memory, (poster) Shirley Pepke, Tamara Kinzer-Ursem, Stefan Mihalas, and Mary B. Kennedy, International Conference on Systems Biology, Stanford University, 2009.
    "Inferring Phylogenies by Confidence Set Optimization," (poster) Shirley Pepke, Davin Butt, Isabelle Nadeau, Andrew   Roger, and Christian Blouin, Workshop and  Mathematics of Evolution and Phylogenetics, Paris, France, June 2005.
    "Genome¬wide Short Sequence Repetition Statistics of Human DNA," (poster) Shirley Pepke, Peter Bickel, and Hugh Salamon, 68th Annual Symposium on         Quantitative Biology, Cold Spring Harbor, NY, May 2003.
    “Computation and Analysis of DNA Subsequence Frequencies,” UC Santa Cruz Bioinformatics Seminar, March 18, 2003.
    "Sensorimotor Integration and Biomorph Control," Bioinspired Engineering of Exploration Systems, Jet Propulsion Laboratory, Pasadena, CA, December 2000.
    "Predictability in Space and Time of Model Earthquake Faults and Earth’s Seismicity," Brookhaven National Laboratory Condensed Matter Theory Seminar, NY, April 3, 1995.
    "Predictability of Model Earthquake Faults and Earth’s Seismicity," Center for Nonlinear Studies Colloquium, Los Alamos, NM, November 1994.
    "Predictability of Self¬organizing Earthquake Fault Models," Dynamics Days '94 ¬ 13th Annual Conference on Chaos and Nonlinear Dynamics, Duke University, Durham, NC, January 1994.

Other Experience

1993 Complex Systems Summer School sponsored by the Santa Fe Institute, Saint John's College, Santa Fe, NM