ChimerDB 2.0—a knowledgebase for fusion genes updated

Abstract

Chromosome translocations and gene fusions are frequent events in the human genome and have been found to cause diverse types of tumor. ChimerDB is a knowledgebase of fusion genes identified from bioinformatics analysis of transcript sequences in the GenBank and various other public resources such as the Sanger cancer genome project (CGP), OMIM, PubMed and the Mitelman’s database. In this updated version, we significantly modified the algorithm of identifying fusion transcripts. Specifically, the new algorithm is more sensitive and has detected 2699 fusion transcripts with high confidence. Furthermore, it can identify interchromosomal translocations as well as the intrachromosomal deletions or inversions of large DNA segments. Importantly, results from the analysis of next-generation sequencing data in the short read archives are incorporated as well. We updated and integrated all contents (GenBank, Sanger CGP, OMIM, PubMed publications and the Mitelman’s database), and the user-interface has been improved to support diverse types of searches and to enhance the user convenience especially in browsing PubMed articles. We also developed a new alignment viewer that should facilitate examining reliability of fusion transcripts and inferring functional significance. We expect ChimerDB 2.0, available at http://ercsb.ewha.ac.kr/fusiongene, to be a valuable tool in identifying biomarkers and drug targets.

Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma

“…Our analyses uncovered a new fusion transcript between the genes BCAM and AKT2 in one HGSC cancer sample (patient S4; Table S1). This fusion transcript is novel and has not been reported (16)(17)(18)(19). The presence of this fusion transcript in patient S4 is supported by eight paired "chimeric" reads, with one read mapping to BCAM and the other to AKT2 (Fig.…”

Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

“…In fact, transcription-induced chimeric RNAs, generated in normal healthy cells, without corresponding genomic rearrangements have been well recognized in the field of genetic research (Akiva, 2005;Fang et al, 2012;Gingeras, 2009;Kim DS, et al, 2007;Kim DS, et al, 2012;Kim P, et al, 2010;Kim RN, et al, 2012;Li et al, 2008;Parra, 2005;Prakash et al, 2010;Thomson et al, 2000;Zhang et al, 2012). However, the existence of transcription-induced chimeric RNAs has not been well appreciated in the cancer research field, where fusion genes play an important role in disease development, progression, and treatment (Edwards, 2010;Mitelman et al, 2007).…”

“…Therefore, USP9Y-TTTY15 is a transcription-induced chimeric RNA (an RNA created in normal cells by combining exons from two or more distinctly known parental genes) (Akiva, 2005;Fang et al, 2012;Gingeras, 2009;Kannan et al, 2011;Kim DS et al, 2007Kim P et al, 2010;Kim RN et al, 2012;Li et al, 2008;Parra, 2005;Prakash et al, 2010;Thomson et al, 2000;Zhang et al, 2012). Linked to this finding, we also investigated the expression of another transcription-induced chimeric RNA previously studied in prostate cancer from Western countries, SLC45A3-ELK4, of which both partner genes lie on the same chromosome within a short genomic distance (1q32) (Maher et al, 2009;Rickman et al, 2009;Zhang et al, 2012).…”

Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency

“…In addition, chimeric RNA products with canonical splice sites and matching annotated exon boundaries are regarded as being less likely to be generated in vitro (Kim et al 2010;Al-Balool et al 2011). We found that the intragenic cases have a significantly higher percentage of candidates with canonical splice sites and matching annotated exon boundaries than the intergenic ones (P-value < 10 À13 ) (Supplemental Table 4).…”

“…Generally, trans-splicing is detected by comparing the reference genomes with ESTs/mRNAs (Shao et al 2006;Li et al 2009;Herai and Yamagishi 2010;Kim et al 2010) or by next-generation sequencing (NGS) of mRNAs (RNA-seq) (McManus et al 2010;Zhang et al 2010;Al-Balool et al 2011;Fang et al 2012). Transsplicing events detected by such means may, however, include a considerable number of false positives that arise from experimental artifacts, such as template switching (McManus et al 2010;Ozsolak and Milos 2011).…”