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UID:submissions.pasc-conference.org_PASC26_sess135_pos133@linklings.com
SUMMARY:P38 - Tracking Mechanistic Evolution Across Brain Tissues and Cell
  Types Using Multiplex Networks
DESCRIPTION:Kenneth Smith (Oak Ridge National Laboratory); Matthew Lane (U
 niversity of Tennessee); Alice Townsend and Jean Merlet (Oak Ridge Nationa
 l Laboratory, University of Tennessee); Anna Vlot and Alana Wells (Oak Rid
 ge National Laboratory); and Daniel Jacobson (Oak Ridge National Laborator
 y, University of Tennessee)\n\nTracking the evolution of biological functi
 on remains a major challenge in computational biology, as existing approac
 hes are often limited to sequence conservation, gene presence, or predefin
 ed pathways. These methods can fail to identify conserved functional mecha
 nisms even though constituent genes change. To address these limitations, 
 we present a network-native framework for tracking functional evolution in
  the brain using large multiplex biological networks.\nWe construct whole-
 brain, brain tissue–specific, and brain cell type–specific multiplexes by 
 integrating hundreds of human biological networks. For each gene, we compu
 te Random Walk with Restart (RWR) embeddings that capture topological cont
 ext within the multiplex. Pairwise distances between embeddings are hierar
 chically clustered to identify data-driven mechanistic modules without rel
 iance on predefined pathways.\nTo assess evolutionary conservation, we int
 egrate comparative genomics data across multiple species and align ortholo
 g presence with modules using phylogenetically ordered heat maps. This ena
 bles quantitative comparison of conserved, diverged, and context-specific 
 mechanisms across biological scales. All RWR and distance matrix computati
 ons are implemented using an MPI-distributed, GPU-accelerated pipeline and
  executed on the Oak Ridge Leadership Computing Facility Frontier supercom
 puter. This framework enables analysis of functional evolution and support
 s informed model organism selection based on conserved biological mechanis
 ms.\n\n
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