License: Creative Commons Attribution 4.0 International license (CC BY 4.0)
When quoting this document, please refer to the following
DOI: 10.4230/LIPIcs.WABI.2022.21
URN: urn:nbn:de:0030-drops-170552
URL: http://dagstuhl.sunsite.rwth-aachen.de/volltexte/2022/17055/
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Simonaitis, Pijus ; Raphael, Benjamin J.

A Maximum Parsimony Principle for Multichromosomal Complex Genome Rearrangements

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LIPIcs-WABI-2022-21.pdf (1.0 MB)

Abstract

Motivation. Complex genome rearrangements, such as chromothripsis and chromoplexy, are common in cancer and have also been reported in individuals with various developmental and neurological disorders. These mutations are proposed to involve simultaneous breakage of the genome at many loci and rejoining of these breaks that produce highly rearranged genomes. Since genome sequencing measures only the novel adjacencies present at the time of sequencing, determining whether a collection of novel adjacencies resulted from a complex rearrangement is a complicated and ill-posed problem. Current heuristics for this problem often result in the inference of complex rearrangements that affect many chromosomes.
Results. We introduce a model for complex rearrangements that builds upon the methods developed for analyzing simple genome rearrangements such as inversions and translocations. While nearly all of these existing methods use a maximum parsimony assumption of minimizing the number of rearrangements, we propose an alternative maximum parsimony principle based on minimizing the number of chromosomes involved in a rearrangement scenario. We show that our model leads to inference of more plausible sequences of rearrangements that better explain a complex congenital rearrangement in a human genome and chromothripsis events in 22 cancer genomes.

BibTeX - Entry

@InProceedings{simonaitis_et_al:LIPIcs.WABI.2022.21,
  author =	{Simonaitis, Pijus and Raphael, Benjamin J.},
  title =	{{A Maximum Parsimony Principle for Multichromosomal Complex Genome Rearrangements}},
  booktitle =	{22nd International Workshop on Algorithms in Bioinformatics (WABI 2022)},
  pages =	{21:1--21:22},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-243-3},
  ISSN =	{1868-8969},
  year =	{2022},
  volume =	{242},
  editor =	{Boucher, Christina and Rahmann, Sven},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/opus/volltexte/2022/17055},
  URN =		{urn:nbn:de:0030-drops-170552},
  doi =		{10.4230/LIPIcs.WABI.2022.21},
  annote =	{Keywords: Genome rearrangements, maximum parsimony, cancer evolution, chromothripsis, structural variation, affected chromosomes}
}

Keywords: Genome rearrangements, maximum parsimony, cancer evolution, chromothripsis, structural variation, affected chromosomes
Collection: 22nd International Workshop on Algorithms in Bioinformatics (WABI 2022)
Issue Date: 2022
Date of publication: 26.08.2022
Supplementary Material: Software: https://github.com/raphael-group/MICRO

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