ChiTaRS-3.1-the enhanced chimeric transcripts and RNA-seq database matched with protein-protein interactions

Abstract

Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints. In this latest version, we have included multiple cross-references to GeneCards, iHop, PubMed, NCBI, Ensembl, OMIM, RefSeq and the Mitelman collection for every entry in the 'Full Collection'. In addition, for every chimera, we have added a predicted Chimeric Protein-Protein Interaction (ChiPPI) network, which allows for easy visualization of protein partners of both parental and fusion proteins for all human chimeras. The database contains a comprehensive annotation for 34 922: chimeric transcripts from eight organisms, and includes the manual annotation of 200 sense-antiSense (SaS) chimeras. The current improvements in the content and functionality to the ChiTaRS database make it a central resource for the study of chimeric transcripts and fusion proteins.

Figure 1.

Improved ChiTaRS-3.1 interface. The improved interface of ChiTaRS-3.1 displays information about fusion proteins, their annotations, cross-links to GeneCards, Splice graphs and ‘ChiPPI predicted’ networks.

Figure 2.

The ChiPPI protein–protein Interaction network for the AFF1/KMT2A fusion protein. (A) The initial PPI networks of parental proteins (AFF1 and KMT2A). (B) The ChiPPI network for the AFF1/KMT2A fusion (chimeraID: AM050775, ‘Full Collection’ and ‘Breakpoints’). The onco-proteins, parental proteins, potential onco-proteins, tumor suppressors and normal proteins are shown in dark-orange, light-orange, yellow, blue and green colors correspondingly. (C) All the missing interactors are shown on the network. The interactions of KMT2A with the tumor suppressors MEN1, SMARCB1 and CBFB and also the interactions of AFF1 with the tumor suppressors EAF1 and SIAH1 are lost upon the fusion. (D) The network of the ‘affected’ interactions, e.g. those changed upon the fusion event. (E) All the interactions that stay unchanged upon the fusion event.