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Complexity and algorithms for copy-number evolution problems

BACKGROUND: Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along...

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Detalles Bibliográficos
Autores principales: El-Kebir, Mohammed, Raphael, Benjamin J., Shamir, Ron, Sharan, Roded, Zaccaria, Simone, Zehavi, Meirav, Zeira, Ron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433102/
https://www.ncbi.nlm.nih.gov/pubmed/28515774
http://dx.doi.org/10.1186/s13015-017-0103-2
Descripción
Sumario:BACKGROUND: Cancer is an evolutionary process characterized by the accumulation of somatic mutations in a population of cells that form a tumor. One frequent type of mutations is copy number aberrations, which alter the number of copies of genomic regions. The number of copies of each position along a chromosome constitutes the chromosome’s copy-number profile. Understanding how such profiles evolve in cancer can assist in both diagnosis and prognosis. RESULTS: We model the evolution of a tumor by segmental deletions and amplifications, and gauge distance from profile [Formula: see text] to [Formula: see text] by the minimum number of events needed to transform [Formula: see text] into [Formula: see text] . Given two profiles, our first problem aims to find a parental profile that minimizes the sum of distances to its children. Given k profiles, the second, more general problem, seeks a phylogenetic tree, whose k leaves are labeled by the k given profiles and whose internal vertices are labeled by ancestral profiles such that the sum of edge distances is minimum. CONCLUSIONS: For the former problem we give a pseudo-polynomial dynamic programming algorithm that is linear in the profile length, and an integer linear program formulation. For the latter problem we show it is NP-hard and give an integer linear program formulation that scales to practical problem instance sizes. We assess the efficiency and quality of our algorithms on simulated instances. AVAILABILITY: https://github.com/raphael-group/CNT-ILP ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13015-017-0103-2) contains supplementary material, which is available to authorized users.