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BEGIN:VEVENT
DTSTAMP:20250822T115805Z
LOCATION:Campussaal - Plenary Room
DTSTART;TZID=Europe/Stockholm:20250617T103000
DTEND;TZID=Europe/Stockholm:20250617T110000
UID:submissions.pasc-conference.org_PASC25_sess150_pos143@linklings.com
SUMMARY:P32 - Multi-Omic Single Cell Network Perturbation for Phenotypic P
 rediction
DESCRIPTION:Matthew Lane (Oak Ridge National Laboratory, University of Ten
 nessee); Erica Prates (Oak Ridge National Laboratory); Alice Townsend and 
 Jean Merlet (Oak Ridge National Laboratory, University of Tennessee); Chri
 stiane Alvarez and Alana Wells (Oak Ridge National Laboratory); and Daniel
  Jacobson (Oak Ridge National Laboratory, University of Tennessee)\n\nDrug
  repurposing offers a cost-effective strategy to identify new applications
  for existing medications, leveraging established safety profiles to accel
 erate therapeutic development. Advances in computational biology and large
 -scale multi-omics data enable systematic identification of novel therapeu
 tic opportunities, addressing unmet medical needs and advancing precision 
 medicine. This study employs a multiplex network integrating 10 literature
 -based layers from the HumanNet database and 320 data-driven predictive ex
 pression networks derived from single-cell RNA sequencing and bulk transcr
 iptomic data. Constructed using the iRF-LOOP algorithm, requiring over 500
 ,000 compute hours on the Frontier supercomputer, this multiplex provides 
 a framework for analyzing gene functions across diverse biological context
 s.\nWe applied the Random Walk with Restart algorithm to compute embedding
 s for 52,722 genes, quantifying their topological relevance within the net
 work. Drug-gene interactions from DrugBank and disease-gene associations f
 rom UKBiobank GWAS were mapped to these embeddings, linking therapeutic ag
 ents to potential targets and revealing biomarkers. A case study on glucag
 on-like peptide 1 receptor (GLP-1R) agonists, initially developed for type
  2 diabetes, identified genes topologically connected to GLP-1R  (TMPRSS2,
  PNPLA3, DHX37, ZNF91, DTHD1, and IRX3) and associated diseases. This stud
 y demonstrates the power of multiplex networks and supercomputing in uncov
 ering connections between genes, drugs, and diseases, offering insights in
 to therapeutic discovery.\n\nSession Chair: David Moxey (King's College Lo
 ndon)\n\n
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