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SUMMARY:The Code Underlying Tissue-Regulated Splicing - Brendan Frey\, Uni
 versity of Toronto
DTSTART:20090511T150000Z
DTEND:20090511T160000Z
UID:TALK17507@talks.cam.ac.uk
CONTACT:Laura Blackburn
DESCRIPTION:Alternative splicing is a mechanism that amplifies the library
  of 22\,000\nhuman genes to up to 1 million transcripts\, most of which ar
 e regulated in\na cell type-dependent fashion. Alternative splicing is kno
 wn to control\nphenotypes such as sexual preference and neural connectivit
 y and many\ndisease mutations occur in splicing regulatory sequence. A cen
 tral goal in\nthe past decade has been to elucidate a 'splicing code': A s
 et of RNA\nfeatures in unspliced transcripts and a function that maps thos
 e features\nto tissue-dependent splicing patterns.\n\nMy group at the Univ
 ersity of Toronto recently introduced a method that\nconstructs a splicing
  code by extracting biologically informative signals\nfrom tissue profilin
 g data and identifying many diverse RNA features that\nin combination are 
 maximally predictive of those signals. Using the\nestimated inclusion leve
 ls of thousands of exons in diverse tissues\, we\ninferred a splicing code
  from 987 putative RNA features. The utility and\naccuracy of the code is 
 supported by experimental validation of\npredictions\, plus feature evalua
 tion using mutated minigene reporters.\nOur code includes previously-studi
 ed and novel features. Regulatory\nsequence identified by our method is lo
 cated deeper into intronic\nsequence than previously expected and the numb
 er of regulatory features\nidentified per regulated exon is surprisingly l
 arge. We believe that this\ncode constitutes a first step in understanding
  the complexity introduced\nby ubiquitous alternative splicing.
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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