Dataset Information

Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies.

ABSTRACT: Chimeric transcripts, including partial and internal tandem duplications (PTDs, ITDs) and gene fusions, are important in the detection, prognosis, and treatment of human cancers.We describe Barnacle, a production-grade analysis tool that detects such chimeras in de novo assemblies of RNA-seq data, and supports prioritizing them for review and validation by reporting the relative coverage of co-occurring chimeric and wild-type transcripts. We demonstrate applications in large-scale disease studies, by identifying PTDs in MLL, ITDs in FLT3, and reciprocal fusions between PML and RARA, in two deeply sequenced acute myeloid leukemia (AML) RNA-seq datasets.Our analyses of real and simulated data sets show that, with appropriate filter settings, Barnacle makes highly specific predictions for three types of chimeric transcripts that are important in a range of cancers: PTDs, ITDs, and fusions. High specificity makes manual review and validation efficient, which is necessary in large-scale disease studies. Characterizing an extended range of chimera types will help generate insights into progression, treatment, and outcomes for complex diseases.

SUBMITTER: Swanson L

PROVIDER: S-EPMC3751903 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies.

Swanson Lucas L Robertson Gordon G Mungall Karen L KL Butterfield Yaron S YS Chiu Readman R Corbett Richard D RD Docking T Roderick TR Hogge Donna D Jackman Shaun D SD Moore Richard A RA Mungall Andrew J AJ Nip Ka Ming KM Parker Jeremy D K JD Qian Jenny Qing JQ Raymond Anthony A Sung Sandy S Tam Angela A Thiessen Nina N Varhol Richard R Wang Sherry S Yorukoglu Deniz D Zhao Yongjun Y Hoodless Pamela A PA Sahinalp S Cenk SC Karsan Aly A Birol Inanc I

BMC genomics 20130814

<h4>Background</h4>Chimeric transcripts, including partial and internal tandem duplications (PTDs, ITDs) and gene fusions, are important in the detection, prognosis, and treatment of human cancers.<h4>Results</h4>We describe Barnacle, a production-grade analysis tool that detects such chimeras in de novo assemblies of RNA-seq data, and supports prioritizing them for review and validation by reporting the relative coverage of co-occurring chimeric and wild-type transcripts. We demonstrate applica ...[more]

PMID: 23941359

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Project description:BackgroundEscherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular) proteins consist of two or more components (modules) encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes.ResultsMultimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused) proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes.ConclusionThe deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes it possible to generate protein groups related by both sequence and function, avoiding mixing of unrelated sequences. Organisms differ in sizes of groups of sequence-related proteins. A sample comparison of orthologs to selected E. coli paralogous groups correlates with known physiological and taxonomic relationships between the organisms.

Dataset Information

Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies.

Publications

Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies.

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