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Identification of genetic markers with synergistic survival effect in cancer

BACKGROUND: Cancers are complex diseases arising from accumulated genetic mutations that disrupt intracellular signaling networks. While several predisposing genetic mutations have been found, these individual mutations account only for a small fraction of cancer incidence and mortality. With large-...

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Autores principales: Louhimo, Riku, Laakso, Marko, Heikkinen, Tuomas, Laitinen, Susanna, Manninen, Pekka, Rogojin, Vladimir, Miettinen, Minna, Blomqvist, Carl, Liu, Jianjun, Nevanlinna, Heli, Hautaniemi, Sampsa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750540/
https://www.ncbi.nlm.nih.gov/pubmed/24267921
http://dx.doi.org/10.1186/1752-0509-7-S1-S2
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author Louhimo, Riku
Laakso, Marko
Heikkinen, Tuomas
Laitinen, Susanna
Manninen, Pekka
Rogojin, Vladimir
Miettinen, Minna
Blomqvist, Carl
Liu, Jianjun
Nevanlinna, Heli
Hautaniemi, Sampsa
author_facet Louhimo, Riku
Laakso, Marko
Heikkinen, Tuomas
Laitinen, Susanna
Manninen, Pekka
Rogojin, Vladimir
Miettinen, Minna
Blomqvist, Carl
Liu, Jianjun
Nevanlinna, Heli
Hautaniemi, Sampsa
author_sort Louhimo, Riku
collection PubMed
description BACKGROUND: Cancers are complex diseases arising from accumulated genetic mutations that disrupt intracellular signaling networks. While several predisposing genetic mutations have been found, these individual mutations account only for a small fraction of cancer incidence and mortality. With large-scale measurement technologies, such as single nucleotide polymorphism (SNP) microarrays, it is now possible to identify combinatorial effects that have significant impact on cancer patient survival. RESULTS: The identification of synergetic functioning SNPs on genome-scale is a computationally daunting task and requires advanced algorithms. We introduce a novel algorithm, Geninter, to identify SNPs that have synergetic effect on survival of cancer patients. Using a large breast cancer cohort we generate a simulator that allows assessing reliability and accuracy of Geninter and logrank test, which is a standard statistical method to integrate genetic and survival data. CONCLUSIONS: Our results show that Geninter outperforms the logrank test and is able to identify SNP-pairs with synergetic impact on survival.
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spelling pubmed-37505402013-08-27 Identification of genetic markers with synergistic survival effect in cancer Louhimo, Riku Laakso, Marko Heikkinen, Tuomas Laitinen, Susanna Manninen, Pekka Rogojin, Vladimir Miettinen, Minna Blomqvist, Carl Liu, Jianjun Nevanlinna, Heli Hautaniemi, Sampsa BMC Syst Biol Research BACKGROUND: Cancers are complex diseases arising from accumulated genetic mutations that disrupt intracellular signaling networks. While several predisposing genetic mutations have been found, these individual mutations account only for a small fraction of cancer incidence and mortality. With large-scale measurement technologies, such as single nucleotide polymorphism (SNP) microarrays, it is now possible to identify combinatorial effects that have significant impact on cancer patient survival. RESULTS: The identification of synergetic functioning SNPs on genome-scale is a computationally daunting task and requires advanced algorithms. We introduce a novel algorithm, Geninter, to identify SNPs that have synergetic effect on survival of cancer patients. Using a large breast cancer cohort we generate a simulator that allows assessing reliability and accuracy of Geninter and logrank test, which is a standard statistical method to integrate genetic and survival data. CONCLUSIONS: Our results show that Geninter outperforms the logrank test and is able to identify SNP-pairs with synergetic impact on survival. BioMed Central 2013-08-12 /pmc/articles/PMC3750540/ /pubmed/24267921 http://dx.doi.org/10.1186/1752-0509-7-S1-S2 Text en Copyright © 2013 Louhimo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Louhimo, Riku
Laakso, Marko
Heikkinen, Tuomas
Laitinen, Susanna
Manninen, Pekka
Rogojin, Vladimir
Miettinen, Minna
Blomqvist, Carl
Liu, Jianjun
Nevanlinna, Heli
Hautaniemi, Sampsa
Identification of genetic markers with synergistic survival effect in cancer
title Identification of genetic markers with synergistic survival effect in cancer
title_full Identification of genetic markers with synergistic survival effect in cancer
title_fullStr Identification of genetic markers with synergistic survival effect in cancer
title_full_unstemmed Identification of genetic markers with synergistic survival effect in cancer
title_short Identification of genetic markers with synergistic survival effect in cancer
title_sort identification of genetic markers with synergistic survival effect in cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750540/
https://www.ncbi.nlm.nih.gov/pubmed/24267921
http://dx.doi.org/10.1186/1752-0509-7-S1-S2
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