{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:33Z","timestamp":1787028573996,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["LP180101334"],"award-info":[{"award-number":["LP180101334"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["LP180101085"],"award-info":[{"award-number":["LP180101085"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["LP190101209"],"award-info":[{"award-number":["LP190101209"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["LP220200614"],"award-info":[{"award-number":["LP220200614"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oz Omics Pty Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The filarioid nematode Dirofilaria immitis is the causative agent of heartworm disease, a major parasitic infection of canids, felids and occasionally humans. Current prevention relies on macrocyclic lactone-based chemoprophylaxis, but the emergence of drug resistance highlights the need for new intervention strategies. Here, we applied a machine learning (ML)-based framework to predict and prioritise essential genes in D. immitis in silico, using genomic, transcriptomic and functional datasets from the model organisms Caenorhabditis elegans and Drosophila melanogaster. With a curated set of 26 predictive features, we trained and evaluated multiple ML models and, using a defined threshold, we predicted 406 \u2018high-priority\u2019 essential genes. These genes showed strong transcriptional activity across developmental stages and were inferred to be enriched in pathways related to ribosome biogenesis, translation, RNA processing and signalling, underscoring their potential as anthelmintic targets. Transcriptomic analyses suggested that these genes are associated with key reproductive and neural tissues, while chromosomal mapping revealed a relatively even genomic distribution, in contrast to patterns observed in C. elegans and Dr. melanogaster. In addition, initial evidence suggested structural variation in the X chromosome compared with a recently published D. immitis assembly, indicating the importance of integrating long-read sequencing with high-throughput chromosome conformation capture (Hi-C) mapping. Overall, this study reinforces the potential of ML-guided approaches for essential gene discovery in parasitic nematodes and provides a foundation for downstream validation and therapeutic target development.<\/jats:p>","DOI":"10.3390\/ijms26209923","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Inference of Essential Genes in Dirofilaria immitis Using Machine Learning"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-848X","authenticated-orcid":false,"given":"T\u00falio L.","family":"Campos","sequence":"first","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Bioinformatics Core Facility, Aggeu Magalh\u00e3es Institute (Fiocruz), Recife 50740-465, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-4674","authenticated-orcid":false,"given":"Pasi K.","family":"Korhonen","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8756-229X","authenticated-orcid":false,"given":"Neil D.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita B.","family":"Sumanam","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Bullard","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health USA Inc., Athens, GA 30601, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health USA Inc., Athens, GA 30601, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-9086","authenticated-orcid":false,"given":"Jiangning","family":"Song","sequence":"additional","affiliation":[{"name":"Faculty of IT, Department of Data Science and AI, Monash University, Clayton, VIC 3800, Australia"},{"name":"Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia"},{"name":"Monash Data Futures Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-4852","authenticated-orcid":false,"given":"Bill C. H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Marh\u00f6fer","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-2636","authenticated-orcid":false,"given":"Paul M.","family":"Selzer","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Animal Health, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-1690","authenticated-orcid":false,"given":"Robin B.","family":"Gasser","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpddr.2021.03.004","article-title":"Heartworm disease\u2014Overview, intervention, and industry perspective","volume":"16","author":"Noack","year":"2021","journal-title":"Int. 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