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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.
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System Biology Gustavo de SouzaIMM, OUS October 2013
Reductionism VS Holism The study of biology through systematic perturbation, global read-out of the multifaceted and integration of thesedata 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 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
Proteomics flex its muscle Mann et al., 2013
Take home message • System biology is a post-genomic field that focus in global changes within a system. • Depends heavily on computational approaches (measurement, statistical validation, integration of thousands of components) • Proteomics is still “under development” compared to Genomics/transcriptomics, but has almost comparable throughput in recent years
Advanced Proteomics Gustavo de SouzaIMM, OUS October 2013
Relevance of the Proteome If a gene is transcripted andits mRNA levels goes up, doesthat necessarily means theprotein level that the mRNAtranslates also goes up?
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
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 transcriptomicsto elucidate functional studies.