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Chimeric RNA transcripts are formed when exons from two different genes are fused together, often due to chromosomal translocations, transcriptional errors or trans-splicing effect. While these chimeric RNAs only produce functional proteins in certain cases, they play a significant role in disease phenotyping and progression. ChiTaRS 5.0 is the latest and most comprehensive chimeric transcript repository, with 111 582 annotated entries from eight species, including 23,167 known human cancer breakpoints. The database includes unique information correlating chimeric breakpoints with 3D chromatin contact maps, generated from public datasets of chromosome conformation capture techniques (Hi–C).
Fusion proteins, comprising peptides derived from the translation of two parental genes, are produced in cancer patients due to chromosomal aberrations. These fusion proteins incorporate domains from both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11,528 cancer fusions (ChiTaRS-3.1). The server chimeric protein–protein interactions (ChiPPI), uses the domain–domain co-occurrence scores to identify preserved interactors of chimeric proteins. Mapping the influence of fusion proteins on cell metabolism and pathways reveals that ChiPPI networks often lose tumor suppressor proteins and gain oncoproteins.
Tailored therapy aims to treat cancer patients effectively and safely, by considering the complex interactions between patients' genomic features, disease pathology and drug metabolism. The growing body of scientific literature highlights the need for efficient data mining methods to improve the extraction of valuable information related to patients' genomic features. An important application of text mining to tailored cancer therapy encompasses the use of mutations and cancer fusion genes as moieties that change patients' cellular networks to develop cancer and affect drug metabolism. Fusion proteins, arising from the fusion of two parental genes, are produced in cancer due to chromosomal aberrations and trans-splicing. By knowing the parental proteins of predicted fusion proteins, we applied our previously developed method to identify chimeric protein–protein interactions (ChiPPIs) associated with these fusion proteins. Our validation approach involves predicting cellular network alterations through ChiPPI and confirming them using our new method, ProtFus, via online literature searches.
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