TY - JOUR
T1 - Identifying simultaneous rearrangements in cancer genomes
AU - Oesper, Layla
AU - Dantas, Simone
AU - Raphael, Benjamin J.
N1 - Funding Information:
L.O. is supported by NSF CRII award [IIS-1657380], S.D. is supported by CAPES Project ID 18316-12-3, CNPq and FAPERJ and B.J.R. is supported by NSF CAREER Award [CCF-1053753] and US National Institutes of Health (NIH) grants [R01HG007069 and U24CA211000].
Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - Motivation The traditional view of cancer evolution states that a cancer genome accumulates a sequential ordering of mutations over a long period of time. However, in recent years it has been suggested that a cancer genome may instead undergo a one-Time catastrophic event, such as chromothripsis, where a large number of mutations instead occur simultaneously. A number of potential signatures of chromothripsis have been proposed. In this work, we provide a rigorous formulation and analysis of the â ability to walk the derivative chromosome' signature originally proposed by Korbel and Campbell. In particular, we show that this signature, as originally envisioned, may not always be present in a chromothripsis genome and we provide a precise quantification of under what circumstances it would be present. We also propose a variation on this signature, the H/T alternating fraction, which allows us to overcome some of the limitations of the original signature. Results We apply our measure to both simulated data and a previously analyzed real cancer dataset and find that the H/T alternating fraction may provide useful signal for distinguishing genomes having acquired mutations simultaneously from those acquired in a sequential fashion.
AB - Motivation The traditional view of cancer evolution states that a cancer genome accumulates a sequential ordering of mutations over a long period of time. However, in recent years it has been suggested that a cancer genome may instead undergo a one-Time catastrophic event, such as chromothripsis, where a large number of mutations instead occur simultaneously. A number of potential signatures of chromothripsis have been proposed. In this work, we provide a rigorous formulation and analysis of the â ability to walk the derivative chromosome' signature originally proposed by Korbel and Campbell. In particular, we show that this signature, as originally envisioned, may not always be present in a chromothripsis genome and we provide a precise quantification of under what circumstances it would be present. We also propose a variation on this signature, the H/T alternating fraction, which allows us to overcome some of the limitations of the original signature. Results We apply our measure to both simulated data and a previously analyzed real cancer dataset and find that the H/T alternating fraction may provide useful signal for distinguishing genomes having acquired mutations simultaneously from those acquired in a sequential fashion.
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U2 - 10.1093/bioinformatics/btx745
DO - 10.1093/bioinformatics/btx745
M3 - Article
C2 - 29186385
AN - SCOPUS:85040628188
SN - 1367-4803
VL - 34
SP - 346
EP - 352
JO - Bioinformatics
JF - Bioinformatics
IS - 2
ER -