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System Biology

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

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  1. System Biology Gustavo de SouzaIMM, OUS October 2013

  2. Scrutinizing global changes

  3. 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.

  4. Integrating “omic” approaches Ge H et al., 2003.

  5. Integrating expression data Ge H et al., 2003.

  6. Comparing data Ge H et al., 2003.

  7. Strategy Ge H et al., 2003.

  8. System Biology in Immunology Amit I et al., 2011

  9. System Biology in Immunology Amit I et al., 2011

  10. System Biology in Immunology Amit I et al., 2011

  11. Obvious Challenges • Signal VS Noise • Biologically relevant VS random effect • Integration of discovery- and hypothesis-driven science • Integration of technology – biology - computation

  12. Proteomics capacity as a System Biology tool

  13. Proteomics capacity as a System Biology tool

  14. Proteomics capacity as a System Biology tool Proteomics can reach 86%of Ids predicted by transcriptomics At the cost of 12 days of analysis

  15. Characterization of 11 cell lines Geiger T et al., 2012

  16. Characterization of 11 cell lines

  17. Characterization of 11 cell lines

  18. Proteomics flex its muscle Mann et al., 2013

  19. 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

  20. Advanced Proteomics Gustavo de SouzaIMM, OUS October 2013

  21. Are mRNA levels comparable to their protein levels?

  22. 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?

  23. Pulse Labeling

  24. Translational machinery saturates

  25. Can one predict protein levels based on mRNA levels? Steen and Mann, 2004

  26. Super-SILAC Geiger T et al., 2010

  27. Spike-In SILAC Geiger T et al., 2013

  28. Good reproducibility

  29. Top 100 Proteome

  30. Brown VS White fat tissue

  31. mRNA VS Protein level

  32. 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.

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