ChiTaRS 8.0: the comprehensive database of chimeric transcripts and RNA-seq data with applications in liquid biopsy.

in Nucleic acids research by Dylan DSouza, Lihi Bik, Olawumi Giwa, Shahaf Cohen, Hilit Levy Barazany, Tali Siegal, Milana Frenkel-Morgenstern

TLDR

  • The study updates the Chimeric Transcripts and RNA-Sequencing database to include novel chimeras and gene fusions, with potential applications in disease diagnosis and therapy.

Abstract

Gene fusions are nucleotide sequences formed due to errors in replication and transcription control. These errors, resulting from chromosomal translocation, transcriptional errors or trans-splicing, vary from cell to cell. The identification of fusions has become critical as key biomarkers for disease diagnosis and therapy in various cancers, significantly influencing modern medicine. Chimeric Transcripts and RNA-Sequencing database version 8.0 (ChiTaRS 8.0; http://biosrv.org/chitars) is a specialized repository for human chimeric transcripts, containing 47 445 curated RNA transcripts and over 100 000 chimeric sequences in humans. This updated database provides unique information on 1055 chimeric breakpoints derived from public datasets using chromosome conformation capture techniques (the Hi-C datasets). It also includes an expanded list of gene fusions that are potential drug targets, and chimeric breakpoints across 934 cell lines, positioning ChiTaRS 8.0 as a valuable resource for testing personalized cancer therapies. By utilizing text mining on a curated selection of disease-specific RNA-sequencing data from public datasets, as well as patient blood and plasma samples, we have identified novel chimeras-particularly in diseases such as oral squamous cell carcinoma and glioblastoma-now catalogued in ChiTaRS. Thus, ChiTaRS 8.0 serves as an enhanced fusion transcript repository that incorporates insights into the functional landscape of chimeras in cancers and other complex diseases, based on liquid biopsy results.

Overview

  • The study focuses on identifying and cataloging chimeric transcripts and gene fusions in the human genome, with potential applications in disease diagnosis and therapy.
  • The Chimeric Transcripts and RNA-Sequencing database version 8.0 (ChiTaRS 8.0) is a repository containing 47,445 curated RNA transcripts and over 100,000 chimeric sequences in humans.
  • The study aims to provide insights into the functional landscape of chimeras in cancers and other complex diseases by analyzing liquid biopsy results and incorporating information on chimeric breakpoints derived from public datasets using chromosome conformation capture techniques (Hi-C datasets).

Comparative Analysis & Findings

  • The study identified novel chimeras-particularly in oral squamous cell carcinoma and glioblastoma-using text mining on a curated selection of disease-specific RNA-sequencing data from public datasets, as well as patient blood and plasma samples.
  • The database includes information on 1055 chimeric breakpoints derived from public datasets and expanded lists of gene fusions that are potential drug targets.
  • The study provides a valuable resource for testing personalized cancer therapies by including chimeric breakpoints across 934 cell lines in ChiTaRS 8.0.

Implications and Future Directions

  • The study's findings have significant implications for disease diagnosis and therapy, particularly in cancers where targeted therapies could be developed based on the identification of specific gene fusions.
  • Future directions could involve expanding the database to include additional disease-specific data and exploring the functional consequences of identified chimeras in cancer biology.
  • Liquid biopsy results could further aid in the detection and monitoring of chimeric transcripts and gene fusions, providing a non-invasive and real-time approach to disease diagnosis.
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