Transcript docs/DatatoBiology - Center for Science of Information

Data to Biology
Shankar Subramaniam
University of California at San Diego
Many Dimensions of Biology
• Scales: Molecules, Networks, Cells, Tissues…
• Granularity: Structure, Function, Phenotype,
Physiology…
• Development: Stem cells, Differentiation, Tissue
Engineering…
• Species: Microorganisms, Unicellular
Eukaryotes, Insects, Plants, Animals…
• Length/Time: fempto, nano, micro, ….
• Cell Processes: Metabolism, Regulation,
Signaling…
• Models: Micro, Meso, Macro….
• Model Systems: Microbes, Yeast, Worm/Fly,
Plant, Mouse, Rat, Human
UCSD-Bioinformatics & Systems Biology Group
CELLULAR RESPONSE TO STIMULUS
Input
•proteins
•peptides
•amino acids
•nucleotides
•retinoids
Cell
State1
State2
State i
Response
Gene
Expression
State: genes, proteins, metabolites, ions……
The Parts List Problem!
UCSD-Bioinformatics & Systems Biology Group
Automated sequencing machines at the Center for Genome
Research in the Whitehead Institute
UCSD-Bioinformatics & Systems Biology Group
Deconstructing Biology
• Analysis of components, interactions and
phenotypes – in context
• Multiscale and high throughput measurements
• Integration of data and knowledge
• Coarse grained views of the system
• Understanding larger scale function
• Quantitative prediction of response to input at the
systems level
• Study of dynamical behavior of systems
• Perturbation of components to produce changes in
systemic response
• Building dynamical models of systems
Challenges in building
biochemical models
• Complexity of proteomic states and
interactions
• Integration of diverse data to infer
biochemical interactions and
modules
• Accounting for the temporal state
of biochemical models
DATA, MEASUREMENTS AND INTEGRATION
Papin, Gianchandani and Subramaniam, Current Opinions in Biotechnology 2004
Characterizing Biochemical Models - Reconstruction
Pradervand, Maurya
and Subramaniam
Genome Biology 2006
Basic Challenges for Systems Biology
• How will we define and characterize a biological
system?
• How can we obtain the information on components
of the system (qualitative and quantitative; static
and dynamical)? Technologies and computational
methods?
• What mechanisms can we infer from the system
behavior?
• What are realistic models of a system?
• How can we measure/compute input-phenotype
characteristics of the system?
• How will the model of the system be validated
experimentally?
Biological Systems and Models - some Examples…
• The Genome as a System
•
Guda et al. MITOPRED: a genome-scale method for prediction of nucleus-encoded mitochondrial proteins.
Bioinformatics. 2004 Jul 22;20(11):1785-94.
• The Cell as a System
•
Maurya et al. Systems biology of macrophages. Adv Exp Med Biol. 2007; 598: 62-79.
• A Biological Process as a System
•
•
Subramaniam et al. The Macrophage Lipidome. 2008.
Ogawa et al. Molecular Determinants of Crosstalk between Nuclear Receptors and Toll-like Receptors.
Cell. 2005 Sep 9;122(5):707-21.
• A Biochemical Pathway as a System
•
Maurya MR and Subramaniam S. A kinetic model for calcium dynamics in RAW 264.7 Cells: 1.
Mechanisms, parameters and dose response. Biophysical Journal. 2007 Aug; 93: 709-728. A kinetic model
for calcium dynamics in RAW 264.7 Cells: 2. Knockdown response and long-term response. Biophysical
Journal. 2007 Aug; 93: 729-740.
• A Functional Module as a System
•
Bornheimer et al. Computational modeling reveals how interplay between components of a GTPase-cycle
module regulates signal transduction. Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15899-904.
• Physiological Function as a System
•
Avidor-Reiss et al. Decoding cilia function: defining specialized genes required for compartmentalized cilia
biogenesis. Cell. 2004 May 14;117(4):527-39.
• An Organ as a System
•
Bhargav et al. Pathways associated with cardiomyogenesis from embryonic stem cells.
• A Disease as a System
•
Sears et al., Insulin Resistance – A systems physiology study Proc. Natl. Acad. Sci. 2009.