Abstract 1070: siderGrimoire: a database of retroCNVs in human tumors and populations

Abstract Background: Retrocopies, also known as processed pseudogenes, are structural variations resulting from the duplication of protein-coding genes via the reverse transcription of their mature messenger RNA by the LINE-1 enzymatic machinery. These retrocopies can be fixed, present in all genomes of a given species, or unfixed—classified here as retroCNVs—when they are polymorphic, either germline or somatic. While fixed retrocopies have been extensively studied, the understanding of retroCNVs remains limited due to the lack of specialized bioinformatics tools for their detection and annotation in DNA sequencing data, as well as curated databases to share findings with the scientific community. Objective: To address this gap, we developed the sideRETRO, a robust computational tool for the identification and annotation of retroCNVs in whole-genome and exome sequencing data. The results of this tool will be made accessible through siderGrimoire, an online, curated database integrating retroCNVs from human populations and cancer samples. Methods: The sideRETRO pipeline, published in Bioinformatics, offers a dedicated approach to detecting non-fixed retroCNVs. Using datasets from the 1000 Genomes Project and The Cancer Genome Atlas (TCGA), siderGrimoire curates retroCNVs across human populations and tumor samples, providing detailed annotations and a user-friendly interface. Results: Initial analyses reveal a comprehensive landscape of retroCNVs, uncovering their prevalence and patterns of events in diverse human populations and cancer types. This resource bridges a critical gap in the availability of retroCNV-specific data for the research community. Conclusion: The siderGrimoire database represents a significant advancement in retroCNV research, providing a valuable tool for studying the role of retrocopies in genetic variation and cancer biology. By integrating large-scale data from key genomic projects, this platform enables new insights into the genomic impacts of retroCNVs, fostering further exploration in human genetics and oncology. Citation Format: Thiago Luiz Miller, Helena Beatriz da Conceição, Pedro Alexandre Galante. siderGrimoire: a database of retroCNVs in human tumors and populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1070.