{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:50Z","timestamp":1753875830120,"version":"3.41.2"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Cryo-electron microscopy (cryo-EM) is a powerful technique for studying macromolecules and holds the potential for identifying kinetically preferred transition sequences between conformational states. Typically, these sequences are explored within two-dimensional energy landscapes. However, due to the complexity of biomolecules, representing conformational changes in two dimensions can be challenging. Recent advancements in reconstruction models have successfully extracted structural heterogeneity from cryo-EM images using higher-dimension latent space. Nonetheless, creating high-dimensional conformational landscapes in the latent space and then searching for preferred paths continues to be a formidable task.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This study introduces an innovative framework for identifying preferred trajectories within high-dimensional conformational landscapes. Our method encompasses the search for the minimum energy path in the graph, where edge weights are determined based on the energy estimation at each node using local density. The effectiveness of this approach is demonstrated by identifying accurate transition states in both synthetic and real-world datasets featuring continuous conformational changes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The CLEAPA package is available at https:\/\/github.com\/tengyulin\/energy_aware_pathfinding\/.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae345","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T19:36:56Z","timestamp":1717616216000},"source":"Crossref","is-referenced-by-count":0,"title":["CLEAPA: a framework for exploring the conformational landscape of cryo-EM using energy-aware pathfinding 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