Title: A hidden Markov model-based approach to reconstructing double minute chromosome amplicons

Authors: Ruslan T. Mardugalliamov; Kamal Al Nasr; Matthew Hayes

Addresses: Department of Computer Science, Tennessee State University, Nashville, 37209, TN, USA ' Department of Computer Science, Tennessee State University, Nashville, 37209, TN, USA ' Department of Physics and Computer Science, Xavier University of Louisiana, New Orleans, Louisiana, 70125, USA

Abstract: 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.

Keywords: double minute; tumour; next generation sequencing; structural variation; cancer.

DOI: 10.1504/IJCBDD.2020.105096

International Journal of Computational Biology and Drug Design, 2020 Vol.13 No.1, pp.5 - 20

Received: 11 Jun 2018
Accepted: 19 Sep 2018

Published online: 13 Feb 2020 *

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