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BACKGROUND: Next-generation sequencing (NGS) tests are integral to oncology care. To address the need for clinical and NGS data management, interpretation, and reporting, we developed iCatalog for the multi-institutional Individualized Cancer Therapy 2/Genomic Assessment Informs Novel Therapy Consortium (GAIN) pediatric precision oncology (PO) study.METHODS: We designed iCatalog as a secure, web-based clinical decision support application that stores and integrates clinical, specimen, and molecular data from multiple sources at the patient level. The knowledge base (KB) and centralized patient/test database are intended to manage information for the 825 patients expected to enroll in the GAIN study. User permissions and access are controlled. Gene- and variant-level interpretation is facilitated through linked external resources and an internal KB that can be updated during application use. iCatalog generates editable, study-specific patient reports for each molecular test.RESULTS: Launched to support the GAIN study, iCatalog integrates genomic data from eight NGS platforms, generates 1002 clinical interpretation reports, and stores data for 1194 tests involving 777 patients with pediatric solid tumors across 133 diagnoses. The KB contains pediatric cancer-specific curations, authored by the research team, spanning 581 genes and 2659 variants (including 2146 single-nucleotide variants and insertions-deletions, 235 copy-number variants, 278 structural variants).CONCLUSIONS: iCatalog is a robust tool designed and proven to support a PO study. It integrates clinical and genomic data to facilitate the clinical interpretation and reporting of variants identified through NGS testing while maintaining a pediatric-specific KB generated during the study. As a scalable, modular platform, iCatalog can accelerate clinical decision-making and elevate PO insights across studies.