AUTHOR=Martelloni Gabriele , Turchi Alessio , Fallerini Chiara , Degl’Innocenti Andrea , Baldassarri Margherita , Olmi Simona , Furini Simone , Renieri Alessandra , GEN-COVID Multicenter study , Mari Francesca , Daga Sergio , Meloni Ilaria , Bruttini Mirella , Croci Susanna , Lista Mirjam , Maffeo Debora , Pasquinelli Elena , Brunelli Giulia , Zguro Kristina , Serio Viola Bianca , Antolini Enrica , Basso Simona Letizia , Minetto Samantha , Rollo Giulia , Rozza Martina , Rina Angela , Tita Rossella , Mencarelli Maria Antonietta , Lo Rizzo Caterina , Pinto Anna Maria , Ariani Francesca , Montagnani Francesca , Tumbarello Mario , Rancan Ilaria , Fabbiani Massimiliano , Bargagli Elena , Bergantini Laura , d’Alessandro Miriana , Cameli Paolo , Bennett David , Anedda Federico , Marcantonio Simona , Scolletta Sabino , Franchi Federico , Mazzei Maria Antonietta , Guerrini Susanna , Conticini Edoardo , Cantarini Luca , Frediani Bruno , Tacconi Danilo , Raffaelli Chiara Spertilli , Emiliozzi Arianna , Feri Marco , Donati Alice , Scala Raffaele , Guidelli Luca , Spargi Genni , Corridi Marta , Nencioni Cesira , Croci Leonardo , Caldarelli Gian Piero , Romani Davide , Piacentini Paolo , Bandini Maria , Desanctis Elena , Cappelli Silvia , Canaccini Anna , Verzuri Agnese , Anemoli Valentina , Pisani Manola , Ognibene Agostino , Lorubbio Maria , Pancrazzi Alessandro , Vaghi Massimo , Monforte Antonella D’Arminio , Miraglia Federica Gaia , Mondelli Mario U. , Mantovani Stefania , Bruno Raffaele , Vecchia Marco , Maffezzoni Marcello , Martinelli Enrico , Girardis Massimo , Busani Stefano , Venturelli Sophie , Cossarizza Andrea , Antinori Andrea , Vergori Alessandra , Rusconi Stefano , Siano Matteo , Gabrieli Arianna , Riva Agostino , Francisci Daniela , Schiaroli Elisabetta , Pallotto Carlo , Parisi Saverio Giuseppe , Basso Monica , Panese Sandro , Baratti Stefano , Scotton Pier Giorgio , Andretta Francesca , Giobbia Mario , Scaggiante Renzo , Gatti Francesca , Castelli Francesco , Quiros-Roldan Eugenia , Antoni Melania Degli , Zanella Isabella , Monica Matteo della , Piscopo Carmelo , Capasso Mario , Russo Roberta , Andolfo Immacolata , Iolascon Achille , Fiorentino Giuseppe , Carella Massimo , Castori Marco , Merla Giuseppe , Squeo Gabriella Maria , Aucella Filippo , Raggi Pamela , Perna Rita , Bassetti Matteo , Biagio Antonio Di , Sanguinetti Maurizio , Masucci Luca , Guarnaccia Alessandra , Valente Serafina , Florio Alex Di , Mandalà Marco , Giorli Alessia , Salerni Lorenzo , Zucchi Patrizia , Parravicini Pierpaolo , Menatti Elisabetta , Trotta Tullio , Giannattasio Ferdinando , Coiro Gabriella , Lena Fabio , Lacerenza Gianluca , Mussini Cristina , Tavecchia Luisa , Crotti Lia , Parati Gianfranco , Menè Roberto , Sanarico Maurizio , Gori Marco , Raimondi Francesco , Stella Alessandra , Biscarini Filippo , Bachetti Tiziana , Rovere Maria Teresa La , Bussotti Maurizio , Ludovisi Serena , Capitani Katia , Dei Simona , Ravaglia Sabrina , Giliberti Annarita , Gori Giulia , Artuso Rosangela , Andreucci Elena , Pagliazzi Angelica , Fiorentini Erika , Perrella Antonio , Bianchi Francesco , Bergomi Paola , Catena Emanuele , Colombo Riccardo , Luchi Sauro , Morelli Giovanna , Petrocelli Paola , Iacopini Sarah , Modica Sara , Baroni Silvia , Micheli Giulia , Falcone Marco , Urso Donato , Tiseo Giusy , Matucci Tommaso , Grassi Davide , Ferri Claudio , Marinangeli Franco , Brancati Francesco , Vincenti Antonella , Borgo Valentina , Lombardi Stefania , Lenzi Mirco , Di Pietro Massimo Antonio , Vichi Francesca , Romanin Benedetta , Attala Letizia , Costa Cecilia , Gabbuti Andrea , Bellucci Alessio , Colaneri Marta , Casprini Patrizia , Pomara Cristoforo , Esposito Massimiliano , Leoncini Roberto , Cirianni Michele , Galasso Lucrezia , Bellini Marco Antonio , Gabbi Chiara , Picchiotti Nicola TITLE=Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features JOURNAL=Frontiers in Genetics VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1362469 DOI=10.3389/fgene.2024.1362469 ISSN=1664-8021 ABSTRACT=

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.