期刊
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
卷 2023, 期 -, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/database/baad069
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In this study, the researchers developed InCliniGene, the first clonal tracking graph database that allows accurate tracking of clones in gene therapy clinical applications and enables data integration. The validation results showed that InCliniGene is highly accurate and scalable.
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 gamma-tracking retroviral insertion sites (gamma-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 gamma-TRIS and generates the graph of clones (nodes) connected by arches if two nodes share common genomic features as defined by the gamma-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 gamma-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.Database URL: https://github.com/calabrialab/InCliniGene
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