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Latent space arithmetic was applied to enhance the representation of chirality, by calculating differences between the original descriptor of a molecule and the descriptor of its enantiomer, or the difference between the original descriptor and the descriptor obtained with the stereochemistry-depleted SMILES string. Machine learning was performed with the Random Forest algorithm applied to a dataset of 3858 molecules extracted from the literature (1929 pairs of enantiomers) to predict the elution order observed on the Chiralpak\u00ae AD-H column, as well as intrinsic structural chirality labels (R\/S or canonical SMILES\u00a0@\/@@). The descriptors derived from the heteroencoders achieved an accuracy of up to 0.75 in the prediction of the elution order, and the fingerprints were superior (0.82). A better predictive ability was observed with the difference LSV descriptors than with the original descriptors.<\/jats:p>","DOI":"10.1186\/s13321-025-01080-7","type":"journal-article","created":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T10:59:33Z","timestamp":1756637973000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of chirality descriptors derived from SMILES heteroencoders"],"prefix":"10.1186","volume":"17","author":[{"given":"Natalia","family":"Baimacheva","sequence":"first","affiliation":[]},{"given":"Xinyue","family":"Gao","sequence":"additional","affiliation":[]},{"given":"Joao","family":"Aires-de-Sousa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"issue":"1","key":"1080_CR1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s42004-025-01423-3","volume":"8","author":"F Mastrolorito","year":"2025","unstructured":"Mastrolorito F, Ciriaco F, Togo MV, Gambacorta N, Trisciuzzi D, Altomare CD, Amoroso N, Grisoni N, Nicolotti O (2025) Fragsmiles as a chemical string notation for advanced fragment and chirality representation. 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