Systems Biology

Biological Sequence Analysis 27803

Meet Your Instructor

• Christopher Workman– CBS-DTU– Regulatory Genomic– Integrative Systems Biology

Schedule for the morning

09:00 – 09:25 Pre-module quiz

09:25 – 09:50 Introduction and Motivation

09:50 – 10:20 Coffee Break

10:20 – 10:50 Interaction networks: data and properties

10:50 – 11:10 Discussion: Pluses/minuses of HTP interaction data sets

11:10 – 12:00 Exercise

Survey/Quiz

What reasons do you think makes Systems Biology a “hot topic”?

• (your answers here…)

What are you most interested in learning about today?

• (your answers here…)

Motivation for Systems Biology

Interest in Systems Biology?

Human genome completed

Pub

Med

abs

trac

ts

Systems biology and emerging properties

Transcriptional regulation of the Cell Cycle

Simon et al. Cell 2001

Boehringer Mannheim metabolic map

Mathematical abstraction of biochemistry

Metabolic models

“Genome scale” metabolic models

• Genes 708• Metabolites 584

– Cytosolic 559– Mitochondrial 164– Extracellular 121

• Reactions 1175– Cytosolic 702– Mitochondrial 124– Exchange fluxes 349

Forster et al. Genome Research 2003.

One framework for Systems Biology

1. The components. Discover all of the genes in the genome and the subset of genes, proteins, and other small molecules constituting the pathway of interest. If possible, define an initial model of the molecular interactions governing pathway function (how?). 

2. Pathway perturbation. Perturb each pathway component through a series of genetic or environmental manipulations. Detect and quantify the corresponding global cellular response to each perturbation.

One framework for Systems Biology

3. Model Reconciliation. Integrate the observed mRNA and protein responses with the current, pathway-specific model and with the global network of protein-protein, protein-DNA, and other known physical interactions.

4. Model verification/expansion. Formulate new hypotheses to explain observations not predicted by the model. Design additional perturbation experiments to test these and iteratively repeat steps (2), (3), and (4).

From model to experiment and back again