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System Biology October 2013 Gustavo de Souza IMM, OUS
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Scrutinizing global changes
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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.
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Integrating “omic” approaches Ge H et al., 2003.
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Integrating expression data Ge H et al., 2003.
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Comparing data Ge H et al., 2003.
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Strategy Ge H et al., 2003.
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System Biology in Immunology Amit I et al., 2011
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System Biology in Immunology Amit I et al., 2011
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System Biology in Immunology
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Obvious Challenges - Signal VS Noise - Biologically relevant VS random effect - Integration of technology – biology - computation - Integration of discovery- and hypothesis-driven science
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Proteomics capacity as a System Biology tool
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Proteomics can reach 86% of Ids predicted by transcriptomics At the cost of 12 days of analysis
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Characterization of 11 cell lines Geiger T et al., 2012
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Characterization of 11 cell lines
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Proteomics flex its muscle Mann et al., 2013
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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
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Advanced Proteomics October 2013 Gustavo de Souza IMM, OUS
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Are mRNA levels comparable to their protein levels?
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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?
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Pulse Labeling
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Translational machinery saturates
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Steen and Mann, 2004 Can one predict protein levels based on mRNA levels?
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Super-SILAC Geiger T et al., 2010
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Spike-In SILAC Geiger T et al., 2013
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Good reproducibility
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Top 100 Proteome
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Brown VS White fat tissue
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mRNA VS Protein level
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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.
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