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DTSTAMP:20260424T140911Z
UID:63d7d8669a9a9907677525@ist.ac.at
DTSTART:20230201T123000
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DESCRIPTION:Speaker: David McCandlish\nhosted by Nick Barton\nAbstract: Sim
 ple models for the relationship between genotype and phenotype can often b
 e restated in terms of an assumption about how the effects of mutations ch
 ange when they occur on different genetic backgrounds. For example\, addit
 ive models correspond to the assumption that the effect of a mutation is i
 ndependent of genetic background\, and pairwise interaction models allow t
 he effects of a mutation to change between genetic backgrounds but assume 
 that the epistatic coefficient between any pair of mutations is background
 -independent. What constraints on the global geometry of the genotype-phen
 otype relationship do these assumptions impose\, and what should we do whe
 n these assumptions are violated? Here I will discuss new statistical meth
 ods for predicting how the effects of mutations change across genetic back
 grounds. By relaxing the assumption of strict global background-independen
 ce of mutational effects to an assumption of approximate local background-
 independence\, we can construct models that behave similarly in many ways 
 to these simple models but which can capture more complex and realistic gl
 obal geometries for the genotype-phenotype relationship. I will illustrate
  these ideas with applications to pre-mRNA splicing and the evolution of k
 aryotypic abnormalities in human cancer.
LOCATION:Online Event ()\, ISTA
ORGANIZER:apal@ist.ac.at
SUMMARY:David McCandlish: Inferring the structure of large empirical fitnes
 s landscapes
URL:https://talks-calendar.ista.ac.at/events/3972
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