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Complexity and algorithms for copy-number evolution problems
Authors:Mohammed El-Kebir  Benjamin J Raphael  Ron Shamir  Roded Sharan  Simone Zaccaria  Meirav Zehavi  Ron Zeira
Institution:1.Department of Computer Science,Princeton University,Princeton,USA;2.Department of Computer Science, Center for Computational Molecular Biology,Brown University,Providence,USA;3.School of Computer Science,Tel Aviv University,Tel Aviv,Israel;4.Dipartimento di Informatica Sistemistica e Comunicazione (DISCo),Univ. degli Studi di Milano-Bicocca,Milan,Italy
Abstract:

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 \(\mathbf {a}\) to \(\mathbf {b}\) by the minimum number of events needed to transform \(\mathbf {a}\) into \(\mathbf {b}\). 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.
Keywords:
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