{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:36:23Z","timestamp":1773160583688,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health in the role of auto-reactive hepatic natural killer cells in the pathogenesis of primary biliary cholangitis","doi-asserted-by":"publisher","award":["PE-2016- 02363915"],"award-info":[{"award-number":["PE-2016- 02363915"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health in the role of auto-reactive hepatic natural killer cells in the pathogenesis of primary biliary cholangitis","doi-asserted-by":"publisher","award":["GR-2018-12367794"],"award-info":[{"award-number":["GR-2018-12367794"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"biocompatible nano-assemblies to increase the safety and the efficacy of steroid treatment against liver inflammation","doi-asserted-by":"publisher","award":["PE-2016- 02363915"],"award-info":[{"award-number":["PE-2016- 02363915"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"biocompatible nano-assemblies to increase the safety and the efficacy of steroid treatment against liver inflammation","doi-asserted-by":"publisher","award":["GR-2018-12367794"],"award-info":[{"award-number":["GR-2018-12367794"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: The application of Machine Learning (ML) to genetic individual-level data represents a foreseeable advancement for the field, which is still in its infancy. Here, we aimed to evaluate the feasibility and accuracy of an ML-based model for disease risk prediction applied to Primary Biliary Cholangitis (PBC). Methods: Genome-wide significant variants identified in subjects of European ancestry in the recently released second international meta-analysis of GWAS in PBC were used as input data. Quality-checked, individual genomic data from two Italian cohorts were used. The ML included the following steps: import of genotype and phenotype data, genetic variant selection, supervised classification of PBC by genotype, generation of \u201cif-then\u201d rules for disease prediction by logic learning machine (LLM), and model validation in a different cohort. Results: The training cohort included 1345 individuals: 444 were PBC cases and 901 were healthy controls. After pre-processing, 41,899 variants entered the analysis. Several configurations of parameters related to feature selection were simulated. The best LLM model reached an Accuracy of 71.7%, a Matthews correlation coefficient of 0.29, a Youden\u2019s value of 0.21, a Sensitivity of 0.28, a Specificity of 0.93, a Positive Predictive Value of 0.66, and a Negative Predictive Value of 0.72. Thirty-eight rules were generated. The rule with the highest covering (19.14) included the following genes: RIN3, KANSL1, TIMMDC1, TNPO3. The validation cohort included 834 individuals: 255 cases and 579 controls. By applying the ruleset derived in the training cohort, the Area under the Curve of the model was 0.73. Conclusions: This study represents the first illustration of an ML model applied to common variants associated with PBC. Our approach is computationally feasible, leverages individual-level data to generate intelligible rules, and can be used for disease prediction in at-risk individuals.<\/jats:p>","DOI":"10.3390\/jpm12101587","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T01:51:49Z","timestamp":1664329909000},"page":"1587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["LLM-PBC: Logic Learning Machine-Based Explainable Rules Accurately Stratify the Genetic Risk of Primary Biliary Cholangitis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-0514","authenticated-orcid":false,"given":"Alessio","family":"Gerussi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damiano","family":"Verda","sequence":"additional","affiliation":[{"name":"Rulex Innovation Labs, Rulex Inc., 16122 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-2967","authenticated-orcid":false,"given":"Claudio","family":"Cappadona","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cristoferi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy"},{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-5428","authenticated-orcid":false,"given":"Davide Paolo","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Bottaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9999-2331","authenticated-orcid":false,"given":"Marco","family":"Muselli","sequence":"additional","affiliation":[{"name":"Rulex Innovation Labs, Rulex Inc., 16122 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-1998","authenticated-orcid":false,"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-0619","authenticated-orcid":false,"given":"Rosanna","family":"Asselta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"IRCCS Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of The Italian PBC Genetics Study 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