BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Felix Held (Chalmers University of Technology & University of Goth enburg) DTSTART:20230608T111500Z DTEND:20230608T120000Z DTSTAMP:20260405T074713Z UID:gbgstats/30 DESCRIPTION:Title: Simultaneous gene clustering and regulatory program reconstruction revea ls insight into the phenotypic plasticity of neural cancers\nby Felix Held (Chalmers University of Technology & University of Gothenburg) as par t of Gothenburg statistics seminar\n\nLecture held in MVL14.\n\nAbstract\n Nervous system cancers contain a large spectrum of transcriptional cell st ates\, reflecting processes active during normal development\, injury resp onse and growth. However\, we lack a good understanding of these states' r egulation and pharmacological importance. Here\, we describe the integrate d reconstruction of such cellular regulatory programs and their therapeuti c targets from extensive collections of single-cell RNA sequencing data (s cRNA-seq). Our approach called single-cell Regulatory-driven Clustering (s cRegClust) performs simultaneous gene clustering and regulatory program re construction tasks to predict essential kinases and transcription factors. We formulate an apriori intractable partitioning problem that connects ge ne modules with linear regulator models. A greedy two-step procedure is co nstructed to iteratively update gene modules and associated regulatory pro grams and find an approximate solution. Penalized regression was used to r eplace a combinatorial selection problem in the construction of regulatory programs and predictive modelling was used during gene cluster allocation . The method is used to identify regulatory programs in tumor cell states from both adult and childhood brain cancers. Further analysis corroborated by experimental results leads to hypothesis generation on an underlying b iological mechanism for drug combination therapy in adult glioblastoma.\n LOCATION:https://researchseminars.org/talk/gbgstats/30/ END:VEVENT END:VCALENDAR