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Identification of genetic markers with synergistic survival effect in cancer.

Louhimo R, Laakso M, Heikkinen T, Laitinen S, Manninen P, Rogojin V, Miettinen M, Blomqvist C, Liu J, Nevanlinna H, Hautaniemi S - BMC Syst Biol (2013)

Bottom Line: 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.Our results show that Geninter outperforms the logrank test and is able to identify SNP-pairs with synergetic impact on survival.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

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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Related in: MedlinePlus

Combinatorial genotypic survival effect. Combination of two markers reveals synergetic effect on survival. The panel inside each figure contains the genotypes and sample sizes. In the right hand survival image, the curve furthest apart (BB, BB) from the rest is for the first marker most distant from curve (BB, AA) and for the second marker from curve (AB, BB).
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Figure 3: Combinatorial genotypic survival effect. Combination of two markers reveals synergetic effect on survival. The panel inside each figure contains the genotypes and sample sizes. In the right hand survival image, the curve furthest apart (BB, BB) from the rest is for the first marker most distant from curve (BB, AA) and for the second marker from curve (AB, BB).

Mentions: For each attribute Mk, 1 ≤ k ≤ e we establish the equivalence relation between curves , as follows: if and only if . For example, the two allele combinations (BB, AA) and (BB, AB) share the feature BB in their attribute M1 for which we can define the equivalence relation (see Figures 3 and 2). Let be a set of equivalence classes for and let have lj equivalence classes (note that lj ≤ m). We can define the distance within an equivalence class with the cluster dendrogram.


Identification of genetic markers with synergistic survival effect in cancer.

Louhimo R, Laakso M, Heikkinen T, Laitinen S, Manninen P, Rogojin V, Miettinen M, Blomqvist C, Liu J, Nevanlinna H, Hautaniemi S - BMC Syst Biol (2013)

Combinatorial genotypic survival effect. Combination of two markers reveals synergetic effect on survival. The panel inside each figure contains the genotypes and sample sizes. In the right hand survival image, the curve furthest apart (BB, BB) from the rest is for the first marker most distant from curve (BB, AA) and for the second marker from curve (AB, BB).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750540&req=5

Figure 3: Combinatorial genotypic survival effect. Combination of two markers reveals synergetic effect on survival. The panel inside each figure contains the genotypes and sample sizes. In the right hand survival image, the curve furthest apart (BB, BB) from the rest is for the first marker most distant from curve (BB, AA) and for the second marker from curve (AB, BB).
Mentions: For each attribute Mk, 1 ≤ k ≤ e we establish the equivalence relation between curves , as follows: if and only if . For example, the two allele combinations (BB, AA) and (BB, AB) share the feature BB in their attribute M1 for which we can define the equivalence relation (see Figures 3 and 2). Let be a set of equivalence classes for and let have lj equivalence classes (note that lj ≤ m). We can define the distance within an equivalence class with the cluster dendrogram.

Bottom Line: 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.Our results show that Geninter outperforms the logrank test and is able to identify SNP-pairs with synergetic impact on survival.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus