TY - JOUR
T1 - A hidden Markov model-based approach to reconstructing double minute chromosome amplicons
AU - Mardugalliamov, Ruslan T.
AU - Al Nasr, Kamal
AU - Hayes, Matthew
N1 - Funding Information:
This publication was made possible by funding from the NIMHD-RCMI grant number 5G12MD007595 from the National Institute on Minority Health and Health Disparities and the NIGMS-BUILD grant number 8UL1GM118967. This publication was also made possible by the Louisiana Cancer Research Consortium. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIMHD
Publisher Copyright:
© 2020 Inderscience Enterprises Ltd.
PY - 2020
Y1 - 2020
N2 - Double minute chromosomes (DMs) are circular fragments of extrachromosomal DNA. They cause extreme gene amplification in the cells of malignant tumours. Their existence correlates with malignant tumour cell behaviour and drug resistance. Locating DMs is important for informing precision therapy to cancer treatment. Furthermore, accurate detection of double minutes requires precise reconstruction of their amplicons, which are the highly-amplified gene-carrying contiguous segments that adjoin to form DMs. This work presents AmpliconFinder - a Hidden-Markov Model-based approach to detect DM amplicons. To assess its efficacy, AmpliconFinder was used to augment an earlier framework for DM detection (DMFinder), thus improving its sensitivity and robustness to noisy sequence data. Experiments on simulated genomic data show that augmenting DMFinder with AmpliconFinder significantly increased the sensitivity of DMFinder on these data. Moreover, DMFinder with AmpliconFinder found all previously reported DMs in three pediatric medulloblastoma datasets, whereas the original DMFinder framework found none.
AB - Double minute chromosomes (DMs) are circular fragments of extrachromosomal DNA. They cause extreme gene amplification in the cells of malignant tumours. Their existence correlates with malignant tumour cell behaviour and drug resistance. Locating DMs is important for informing precision therapy to cancer treatment. Furthermore, accurate detection of double minutes requires precise reconstruction of their amplicons, which are the highly-amplified gene-carrying contiguous segments that adjoin to form DMs. This work presents AmpliconFinder - a Hidden-Markov Model-based approach to detect DM amplicons. To assess its efficacy, AmpliconFinder was used to augment an earlier framework for DM detection (DMFinder), thus improving its sensitivity and robustness to noisy sequence data. Experiments on simulated genomic data show that augmenting DMFinder with AmpliconFinder significantly increased the sensitivity of DMFinder on these data. Moreover, DMFinder with AmpliconFinder found all previously reported DMs in three pediatric medulloblastoma datasets, whereas the original DMFinder framework found none.
KW - Cancer
KW - Double minute
KW - Next generation sequencing
KW - Structural variation
KW - Tumour
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U2 - 10.1504/IJCBDD.2020.105096
DO - 10.1504/IJCBDD.2020.105096
M3 - Article
AN - SCOPUS:85079893833
SN - 1756-0756
VL - 13
SP - 5
EP - 20
JO - International Journal of Computational Biology and Drug Design
JF - International Journal of Computational Biology and Drug Design
IS - 1
ER -
