Barnacle: detecting and characterizing tandem duplications and fusions in transcriptome assemblies.
BACKGROUND
Chimeric transcripts, including partial and internal tandem duplications (PTDs, ITDs) and gene fusions, are important in the detection, prognosis, and treatment of human cancers.


RESULTS
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.


CONCLUSIONS
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.
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
Lucas
L
Swanson
Gordon
G
Robertson
Karen L
KL
Mungall
Yaron S
YS
Butterfield
Readman
R
Chiu
Richard D
RD
Corbett
T Roderick
TR
Docking
Donna
D
Hogge
Shaun D
SD
Jackman
Richard A
RA
Moore
Andrew J
AJ
Mungall
Ka Ming
KM
Nip
Jeremy D K
JD
Parker
Jenny Qing
JQ
Qian
Anthony
A
Raymond
Sandy
S
Sung
Angela
A
Tam
Nina
N
Thiessen
Richard
R
Varhol
Sherry
S
Wang
Deniz
D
Yorukoglu
Yongjun
Y
Zhao
Pamela A
PA
Hoodless
S Cenk
SC
Sahinalp
Aly
A
Karsan
Inanc
I
Birol
D001943:Breast Neoplasms / Q000235:genetics; D005091:Exons / Q000235:genetics; D020440:Gene Duplication / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D050939:Gene Fusion / Q000235:genetics*; D023281:Genomics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D058977:Molecular Sequence Annotation; D012333:RNA, Messenger / Q000235:genetics; D013223:Statistics as Topic
D012333:RNA, Messenger