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Bioinformatic analyses can be used to predict both host\u2010parasite PPIs and potential drug targets in parasite genomes, but high\u2010quality genomic data remain scarce for parasitic monogenean flatworms. Herein, an experimental lineage of\n                    <jats:italic>Gyrodactylus kobayashii<\/jats:italic>\n                    (Monopisthocotylea: Gyrodactylidae) is set up on goldfish hosts and used to conduct phased genome assembly using long\u2010range PacBio HiFi and Hi\u2010C technologies. In silico analyses of genomes of three\n                    <jats:italic>Gyrodactylus<\/jats:italic>\n                    species identified innexins as the most promising novel drug candidate genes. Drug screening and experimental verification singled out Imatinib as the most promising drug targeting innexins, with a high efficiency against\n                    <jats:italic>G. kobayashii<\/jats:italic>\n                    (100% mortality at 25\u00a0\u00b5M within 6\u00a0h in vitro) and low toxicity to the host. Prediction of PPIs in three\n                    <jats:italic>Gyrodactylus<\/jats:italic>\n                    \u2010host pairs revealed proteins associated with cAMP\u2010dependent signaling as key candidates, including the host's PRKACB and the parasite's PRKAR2A, RAP1A, ULK2, and Catenin Beta\u20102. Two interacting G proteins are also identified: GNAO1 and GNB5. As the first high\u2010quality phased chromosome\u2010level genomic assembly for \u201cmonogeneans\u201d and the first identification of PPIs in a fish\u2010parasite system, this study significantly advances the understanding of host\u2010parasite interactions at the genomic level.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514618","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T09:50:19Z","timestamp":1759139419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome\u2010Wide Protein Interaction Analysis in Parasitic Gyrodactylus Flatworms\u2013Fish Hosts System and Drug Target Identification"],"prefix":"10.1002","volume":"12","author":[{"given":"Dong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Herbage Improvement and Grassland Agro\u2010ecosystems and College of Ecology Lanzhou University  Lanzhou Gansu 730000 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