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SUMMARY:Understanding regulatory systems and mechanisms of genetic interac
 tions: from yeast to pediatric cancer - Dr Patrick Kemmeren from Princess 
 Maxima Center in Utrecht\, Netherlands 
DTSTART:20200720T103000Z
DTEND:20200720T113000Z
UID:TALK149800@talks.cam.ac.uk
CONTACT:Anna Toporska
DESCRIPTION:To understand regulatory systems\, it is useful to systematica
 lly determine how individual genes contribute to the expression of all oth
 er genes. We have therefore monitored genome-wide mRNA expression for indi
 vidual deletions of one-quarter of yeast genes. By including gene expressi
 on profiles of double deletions\, we could also investigate genetic intera
 ctions\, a phenomenon where combinations of mutations lead to unexpected e
 ffects. Understanding mechanisms of genetic interactions is important for 
 deciphering pathway architecture as well as understanding the relationship
  between genetic variation and disease. To decipher potential mechanisms w
 e have employed modelling approaches using Boolean networks and Petri Net 
 modelling where genes are represented as nodes and relationships between g
 enes as edges. This allowed over 9 million possible models to be enumerate
 d and exposed that a quantitative edge difference is a strict requirement 
 to explain inversion\, a previously uncharacterized genetic interaction pa
 ttern. Genetic interactions between mutated genes likely play an important
  role in cancer onset and progression. Little is however known about the g
 enetic interactions within pediatric cancer. To create an initial map of p
 otential genetic interactions within cancer and further study their underl
 ying mechanisms\, we have analysed close to 2\,600 childhood tumours for m
 utually exclusive or co-occurring interactions between the different cance
 r types. This map also provides a solid starting point to select candidate
 s for experimental validation as well as extending the analyses to investi
 gate the contribution of genetic interactions towards structural variants\
 , genetic predisposition and cellular pathways. 
LOCATION:ZOOM (live)
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