{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T22:26:51Z","timestamp":1757456811845,"version":"3.41.2"},"reference-count":53,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":306,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TTEMB0322TT"],"award-info":[{"award-number":["TTEMB0322TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2016- 02363681"],"award-info":[{"award-number":["GR-2016- 02363681"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TTEMB0322TT"],"award-info":[{"award-number":["TTEMB0322TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2016- 02363681"],"award-info":[{"award-number":["GR-2016- 02363681"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>High-throughput clonal tracking in patients under hematopoietic stem cell gene therapy with integrating vector is instrumental in assessing bio-safety and efficacy. Monitoring the fate of millions of transplanted clones and their progeny across differentiation and proliferation over time leverages the identification of the vector integration sites, used as surrogates of clonal identity. Although \u03b3-tracking retroviral insertion sites (\u03b3-TRIS) is the state-of-the-art algorithm for clonal identification, the computational drawbacks in the tracking algorithm, based on a combinatorial all-versus-all strategy, limit its use in clinical studies with several thousands of samples per patient. We developed the first clonal tracking graph database, InCliniGene (https:\/\/github.com\/calabrialab\/InCliniGene), that imports the output files of \u03b3-TRIS and generates the graph of clones (nodes) connected by arches if two nodes share common genomic features as defined by the \u03b3-TRIS rules. Embedding both clonal data and their connections in the graph, InCliniGene can track all clones longitudinally over samples through data queries that fully explore the graph. This approach resulted in being highly accurate and scalable. We validated InCliniGene using an in vitro dataset, specifically designed to mimic clinical cases, and tested the accuracy and precision. InCliniGene allows extensive use of \u03b3-TRIS in large gene therapy clinical applications and naturally realizes the full data integration of molecular and genomics data, clinical and treatment measurements and genomic annotations. Further extensions of InCliniGene with data federation and with application programming interface will support data mining toward precision, personalized and predictive medicine in gene therapy.<\/jats:p>\n               <jats:p>Database URL: \u00a0https:\/\/github.com\/calabrialab\/InCliniGene<\/jats:p>","DOI":"10.1093\/database\/baad069","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:52:59Z","timestamp":1699404779000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>InCliniGene<\/i> enables high-throughput and\u00a0comprehensive <i>in vivo<\/i> clonal tracking toward clinical genomics data integration"],"prefix":"10.1093","volume":"2023","author":[{"given":"Ivan","family":"Merelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Beretta","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Cesana","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Gennari","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Benedicenti","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Spinozzi","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Cesini","sequence":"additional","affiliation":[{"name":"Centro Nazionale Analisi Fotogrammi (CNAF), Istituto Nazionale di Fisica Nucleare , Viale Carlo Berti Pichat 6\/2, Bologna 40127, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Montini","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Dipartimento di Informatica, Bioingegneria, Robotica e Ingegneria dei Sistemi (DIBRIS), Universit\u00e0 degli Studi di Genova , Viale Causa 13, Genoa 16145, Italy"},{"name":"Institute of Biomedical Technologies, Italian National Research Council , Via Fratelli Cervi 93, Segrate (MI) 20054, Italy"},{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-3384","authenticated-orcid":false,"given":"Andrea","family":"Calabria","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele , Via Olgettina 60, Milano 20132, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"2023110800523521800_R1","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.cell.2020.08.030","article-title":"Unraveling hematopoiesis through the lens of\u00a0genomics","volume":"182","author":"Liggett","year":"2020","journal-title":"Cell"},{"key":"2023110800523521800_R2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.omtm.2020.03.021","article-title":"DNA barcoding in\u00a0nonhuman primates reveals important limitations in\u00a0retrovirus integration site analysis","volume":"17","author":"Adair","year":"2020","journal-title":"Mol. 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