Ruedi Aebersold - The proteome in context
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 27/03/2018

The  question  how  genetic  variability  is  translated  into  phenotypes  is  fundamental  in  biology  and medicine. Powerful genomic technologies now determine genetic variability at a genomic level and at unprecedented speed, accuracy and (low) cost.  Concurrently, life style monitoring devices and 
improved clinical diagnostic and imaging technologies generate an even larger amount of phenotypic information.   However,   the   molecular   mechanisms   that   translate   genotypic   variability   into phenotypes  are  poorly  understoodand  it  has  been challenging  to  generally  make  phenotypic predictions from genomic information alone. 
The  generation  of  a  general  model  or  theory  that  makes  accurate  predictions  of  the  effects  of genotypic variability on a cell or organism seems out of reach, at least for the intermediate future. 
We therefore propose that the precise measurement of molecular patterns that best reflect the functional response of cells to (genomic) perturbations would have great scientific significance.  We define  the  term “proteotype”  as  a  particular  instance  of  a  proteome  in  terms  of  its  protein composition and organization of proteins into functional modules. 
In the presentation we will discuss recent advances in SWATH/DIA mass spectrometry that support the fast, accurate and reproducible measurement of proteotypes. We will show with specific case studies  that i) the proteotype is highly modular, ii)  genotypic changes cause complex proteotype changes  and iii) that altered proteotypes affect phenotypes. 
Overall, the presentation will introduce the proteotype as a close indicator of the biochemical state of a cell that reflects the response of the cell to (genomic) perturbation and is strong determinant of phenotypes.