System Biology
Gustavo de Souza
IMM, OUS
October 2013
Scrutinizing global changes
Reductionism VS Holism
The study of biology through systematic perturbation,
global read-out of the multifaceted and integration of these
data to formulate predictive models
Ideker et al., Annu. Rev. Genomics Hum. Genet. 2:343-72, 2001.
Integrating “omic” approaches
Ge H et al., 2003.
Integrating expression data
Ge H et al., 2003.
Comparing data
Ge H et al., 2003.
Strategy
Ge H et al., 2003.
System Biology in Immunology
Amit I et al., 2011
System Biology in Immunology
Amit I et al., 2011
System Biology in Immunology
Amit I et al., 2011
Obvious Challenges
- Signal VS Noise
- Biologically relevant VS random effect
- Integration of discovery- and hypothesis-driven science
- Integration of technology – biology - computation
Proteomics capacity as a System Biology tool
Proteomics capacity as a System Biology tool
Proteomics capacity as a System Biology tool
Proteomics can reach 86%
of Ids predicted by transcriptomics
At the cost of 12 days of analysis
Characterization of 11 cell lines
Geiger T et al., 2012
Characterization of 11 cell lines
Characterization of 11 cell lines
Proteomics flex its muscle
Mann et al., 2013
Take home message
1. System biology is a post-genomic field that focus in
global changes within a system.
2. Depends heavily on computational approaches
(measurement, statistical validation, integration of
thousands of components)
3. Proteomics is still “under development” compared to
Genomics/transcriptomics, but has almost comparable
throughput in recent years
Advanced Proteomics
Gustavo de Souza
IMM, OUS
October 2013
Are mRNA levels comparable to their protein levels?
Relevance of the Proteome
If a gene is transcripted and
its mRNA levels goes up, does
that necessarily means the
protein level that the mRNA
translates also goes up?
Pulse Labeling
Translational machinery saturates
Can one predict protein levels based on mRNA levels?
Steen and Mann, 2004
Super-SILAC
Geiger T et al., 2010
Spike-In SILAC
Geiger T et al., 2013
Good reproducibility
Top 100 Proteome
Brown VS White fat tissue
mRNA VS Protein level
Take home message
- As a descriptive data, proteomics is almost as throughput as
transcriptomics (the catch 22 is: it does require very high level
of expertise to perform proteomics at higher standards).
- Proteomics is arguably more appropriate than transcriptomics
to elucidate functional studies.