Detection of structural variations in densely-labelled optical DNA barcodes : A hidden Markov model approach
(2021) In PLoS ONE 16(11 November).- Abstract
Large-scale genomic alterations play an important role in disease, gene expression, and chromosome evolution. Optical DNA mapping (ODM), commonly categorized into sparsely-labelled ODM and densely-labelled ODM, provides sequence-specific continuous intensity profiles (DNA barcodes) along single DNA molecules and is a technique well-suited for detecting such alterations. For sparsely-labelled barcodes, the possibility to detect large genomic alterations has been investigated extensively, while densely-labelled barcodes have not received as much attention. In this work, we introduce HMMSV, a hidden Markov model (HMM) based algorithm for detecting structural variations (SVs) directly in densely-labelled barcodes without access to sequence... (More)
Large-scale genomic alterations play an important role in disease, gene expression, and chromosome evolution. Optical DNA mapping (ODM), commonly categorized into sparsely-labelled ODM and densely-labelled ODM, provides sequence-specific continuous intensity profiles (DNA barcodes) along single DNA molecules and is a technique well-suited for detecting such alterations. For sparsely-labelled barcodes, the possibility to detect large genomic alterations has been investigated extensively, while densely-labelled barcodes have not received as much attention. In this work, we introduce HMMSV, a hidden Markov model (HMM) based algorithm for detecting structural variations (SVs) directly in densely-labelled barcodes without access to sequence information. We evaluate our approach using simulated data-sets with 5 different types of SVs, and combinations thereof, and demonstrate that the method reaches a true positive rate greater than 80% for randomly generated barcodes with single variations of size 25 kilobases (kb). Increasing the length of the SV further leads to larger true positive rates. For a real data-set with experimental barcodes on bacterial plasmids, we successfully detect matching barcode pairs and SVs without any particular assumption of the types of SVs present. Instead, our method effectively goes through all possible combinations of SVs. Since ODM works on length scales typically not reachable with other techniques, our methodology is a promising tool for identifying arbitrary combinations of genomic alterations.
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- author
- Dvirnas, Albertas LU ; Stewart, Callum ; Müller, Vilhelm ; Bikkarolla, Santosh Kumar ; Frykholm, Karolin ; Sandegren, Linus ; Kristiansson, Erik ; Westerlund, Fredrik and Ambjörnsson, Tobias LU
- organization
- publishing date
- 2021-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 16
- issue
- 11 November
- article number
- e0259670
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:34739528
- scopus:85118993476
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0259670
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 Dvirnas et al.
- id
- 56ca934a-033c-4789-b9fe-8abda0c88a04
- date added to LUP
- 2021-12-03 14:28:10
- date last changed
- 2024-08-11 02:54:12
@article{56ca934a-033c-4789-b9fe-8abda0c88a04, abstract = {{<p>Large-scale genomic alterations play an important role in disease, gene expression, and chromosome evolution. Optical DNA mapping (ODM), commonly categorized into sparsely-labelled ODM and densely-labelled ODM, provides sequence-specific continuous intensity profiles (DNA barcodes) along single DNA molecules and is a technique well-suited for detecting such alterations. For sparsely-labelled barcodes, the possibility to detect large genomic alterations has been investigated extensively, while densely-labelled barcodes have not received as much attention. In this work, we introduce HMMSV, a hidden Markov model (HMM) based algorithm for detecting structural variations (SVs) directly in densely-labelled barcodes without access to sequence information. We evaluate our approach using simulated data-sets with 5 different types of SVs, and combinations thereof, and demonstrate that the method reaches a true positive rate greater than 80% for randomly generated barcodes with single variations of size 25 kilobases (kb). Increasing the length of the SV further leads to larger true positive rates. For a real data-set with experimental barcodes on bacterial plasmids, we successfully detect matching barcode pairs and SVs without any particular assumption of the types of SVs present. Instead, our method effectively goes through all possible combinations of SVs. Since ODM works on length scales typically not reachable with other techniques, our methodology is a promising tool for identifying arbitrary combinations of genomic alterations.</p>}}, author = {{Dvirnas, Albertas and Stewart, Callum and Müller, Vilhelm and Bikkarolla, Santosh Kumar and Frykholm, Karolin and Sandegren, Linus and Kristiansson, Erik and Westerlund, Fredrik and Ambjörnsson, Tobias}}, issn = {{1932-6203}}, language = {{eng}}, number = {{11 November}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{Detection of structural variations in densely-labelled optical DNA barcodes : A hidden Markov model approach}}, url = {{http://dx.doi.org/10.1371/journal.pone.0259670}}, doi = {{10.1371/journal.pone.0259670}}, volume = {{16}}, year = {{2021}}, }