Our group investigates integrative approaches to combine functional and systems level knowledge with more traditional omics data and annotation information. We apply a wide range of tools including network inference, machine learning, topological analysis and multi-scale simulation. Simulation studies have included models at the level of molecules, subcellular pathways, cells, tissues and organisms. Recent work has focused on next generation sequencing techniques based on nanopores and on methods to better verify systems biology research.
Research Topics
The Dream Project: The Dialogue on Reverse Engineering Assessments and Methods (DREAM) is a project designed to evaluate model predictions and pathway inference algorithms in systems biology. As its ancestor Critical Assessment of Protein Structure Prediction (CASP), DREAM is structured in the form of challenges, that comprise open problems presented to the community, whose solutions (the “gold standards”) are known to the organizers but not to the participants. Participants submit their predictions of the solutions to the challenges, which are evaluated by the organizers and eventually discussed in a conference after which data, predictions and gold standards are published in a peer-reviewed journal and made openly available to the community. The DREAM challenges aim to address fundamental questions in systems biology, bridging theory and experimentation. The questions posed by DREAM are not simple; to deduce the structure of a biological network based on experimental data, for example, researchers test a variety of algorithms. DREAM allows researchers to compare the strengths and weaknesses of these methods and provides a sense of reliability. It is interesting to note that the combined community predictions are extremely robust and usually the most accurate DREAM challenges highlight the areas where systems biology methods for a mechanistic understanding of biological systems are adequate and those that need to be revised. DREAM proves that rigorous scrutiny of scientific research based on community involvement is possible.
Recent Publications:
- The PLoS Collection of DREAM papers
- R.J. Prill, J. Saez-rodriguez, L.G. Alexopoulos, P.K. Sorger, G. Stolovitzky Crowdsourcing network inference: the DREAM predictive signaling network challenge. Science signaling, 4(189),mr7,2011.
- R.J. Prill, D. Marbach, J. Saez-rodriguez, P.K. Sorger, L.G. Alexopoulos, X. Xue, N.D. Clarke, G. Altan-bonnet, G. Stolovitzky Towards a rigorous assessment of systems biology models: the DREAM3 challenges. PloS one, 5(2),e9202,2010.
- G. Stolovitzky, R.J. Prill, A. Califano Lessons from the DREAM2 ChallengesAnnals Of The New York Academy Of Sciences,1158(1),159--195,2009.
In the News:
- DREAM6 Breaks New Ground August 2, 2011.
- Q&A: IBM's Gustavo Stolovitzky on DREAM 5 Challenges and the Evolution of Reverse Engineering July 23, 2010.
- Math Lens Sharpens Biological Picture:Scientific Challenge Supports Competing Views of Complex Living Systems January 8, 2010
- DREAM Project Vision Expands April 16, 2009.
- More news on DREAM.
Upcoming DREAM 7:
- DREAM7 Conference:Nov 12-16, 2012: 5th RECOMB Conference on Regulatory and Systems Genomics and DREAM Challenges
- DREAM7 Challenges: This year we will have 4 DREAM challenges. We will post the nature of the challenges in the mid to late June time frame (details will be communicated at a later time).
- Challenge submission deadline: October 1st, 2012
IMPROVER: The IMPROVER project is aimed at enhanced assessment of complex scientific processes and establishing Systems Biology Verification as one of the components of science-based decision making. IMPROVER encourages collaborative evaluation of scientific data and plans to establish a broad community of scientists that use processes of verification and community-based problem solving techniques in systems biology. IMPROVER is intended to complement the traditional peer review process through development of a robust, repeatable and recognized methodology to verify the correctness of basic assumptions and methods used in systems biology.
In the News:
- See the latest challenge: Diagnostics Signature Challenge
Recent Publications:
- P. Meyer, L.G. Alexopoulos, T. Bonk, A. Califano, C.R. Cho, A. de la Fuente, D. de Graaf, A.J. Hartemink, J. Hoeng, N.V Ivanov, H. Koeppl, R. Linding, D. Marbach, R. Norel, M.C. Peitsch, J.J. Rice, A. Royyuru, F. Schacherer, J. Sprengel, K. Stolle, D. Vitkup, G. Stolovitzky Verification of systems biology research in the age of collaborative competition. Nature Biotechnology 29, 811-815. (2011).
- P. Meyer, J. Hoeng, R. Norel, J. Sprengel, K. Stolle, T. Bonk, S. Corthesy, A. Royyuru, M.C. Peitsch, , J.J. Rice and G. Stolovitzky Industrial Methodology for Process Verification in Research (IMPROVER): Towards Systems Biology Verification. Bioinformatics (2012).
Multiscale Cardiac Modeling: Multiscale cardiac modeling focuses three main areas: 1) tissue-level models of electrophysiology, 2) models of myofilaments, the basic functional unit of contraction, and 3) organ-level models of electromechanics. Each area requires its own mathematical formulations and computational approached for tractable solutions in timescales appropriate for basic science and clinical applications. In the IBM Cardioid Heart Modeling Project, we develop codes that run on the Blue Gene series of computers that have been ranked some of the fasted computers in the world. We also work with a diverse set of collaborators to understand basic physiology from the molecule level to the whole organism.
Recent Publications:
- B.J. Pope, B.G. Fitch, M.C. Pitman, J.J. Rice, M. Reumann Performance of hybrid programming models for multiscale cardiac simulations: preparing for petascale computation.IEEE Trans Biomed Eng. 2011 Oct;58(10):2965-9
- M. Reumann, B.G. Fitch, A. Rayshubskiy, M.C. Pitman, J.J. Rice Orthogonal recursive bisection as data decomposition strategy for massively parallel cardiac simulations.Biomed Tech (Berl). Jun;56(3):129-45 (2011).
- C. Jons, J. O-Uchi, A.J. Moss, M. Reumann, J.J. Rice, I. Goldenberg, W. Zareba, A.A. Wilde, W. Shimizu, J.K. Kanters, S. McNitt, N. Hofman, J.L. Robinson, C.M. Lopes Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients.Sci Transl Med. 2011.
DNA Transistor: A vast amount of untapped information is held in the DNA of living things, and being able to sequence DNA at a reasonable cost is of great interest to the scientific and medical communities. The IBM approach, called the DNA Transistor, integrates metal electrodes within a nanopore with the goal to control DNA motion. In an effort to build a nanoscale DNA sequencer, IBM scientists are drilling nano-sized holes in computer-like chips and passing DNA strands through them in order to read the information contained within their genetic code. This research effort is to design a silicon-based DNA Transistor that could help pave the way to easily and quickly read human DNA, generating advancements in health condition diagnosis and treatment. The challenge in the effort is to slow the flow of the DNA through the hole so the reader can accurately decode what is in the DNA. If successful, the project could improve throughput and reduce cost to achieve the vision of personalized genome analysis at a cost of $100 to $1,000. In comparison, the first sequencing ever done by the Human Genome Project (HGP) cost $3 billion. A human genome sequencing capability affordable for individuals is the ultimate goal of the DNA sequencing and is commonly referred to as $1,000 genome. Ultimately, it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine and those who are most at risk of adverse reactions.
Recent Publications:
- B. Luan, G. Stolovitzky, G. Martyna Slowing and controlling the translocation of DNA in a solid-state nanopore. Nanoscale, The Royal Society of Chemistry, 2012.
- B. Luan, G. Martyna, G. Stolovitzky Characterizing and Controlling the Motion of ssDNA in a Solid-State Nanopore. Biophysical Journal, Elsevier, 2011
- H. Peng, B. Luan, S. Plonsky, S. Rossnagel, G. Stolovitzky Development of an electrical nanopore device towards the control of the translocation of DNA with single base resolution. Bulletin of the American Physical Society, APS, 2011.
In the News:
- IBM's Killer Idea: The $100 DNA-Sequencing Machine November 16, 2011.
- IBM's 'DNA transistor' January 7, 2010.
- 'DNA Transistor' Could Revolutionize Genetic Testing October 6, 2009.