Evidence map›Paper›PMID 24475110›Full record

ArticlePloS one2014

A new mathematical model for the interpretation of translational research evaluating six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon.

Petr Pancoska, John M Kirkwood, Spyros Bouros, Maria Spyropoulou-Vlachou, Eirini Pectasides, Dimosthenis Tsoutsos, Aristidis Polyzos, Christos Markopoulos, Petros Panagiotou, Ourania Castana and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed, 3 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Petr PancoskaDepartment of Medicine, Center for Clinical Pharmacology, Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
John M KirkwoodDepartment of Medicine, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of America.
Spyros Bouros1st Department of Medicine, Medical School, University of Athens, Athens, Greece.
Maria Spyropoulou-VlachouDepartment of Immunology, National Tissue Typing Center, General Hospital of Athens, Athens, Greece.
Eirini Pectasides1st Department of Medicine, Medical School, University of Athens, Athens, Greece.
Dimosthenis TsoutsosDepartment of Plastic Surgery and Microsurgery, G. Gennimatas General Hospital of Athens, Athens, Greece.
Aristidis Polyzos1st Department of Medicine, Medical School, University of Athens, Athens, Greece.
Christos Markopoulos1st Department of Medicine, Medical School, University of Athens, Athens, Greece.
Petros PanagiotouDepartment of Plastic Surgery and Microsurgery, G. Gennimatas General Hospital of Athens, Athens, Greece.
Ourania CastanaDepartment of Plastic Surgery, Evangelismos General Hospital of Athens, Athens, Greece.
Dimitrios BafaloukosHellenic Cooperative Oncology Group, Data Office, Athens, Greece.
George FountzilasHellenic Cooperative Oncology Group, Data Office, Athens, Greece.
Helen Gogas1st Department of Medicine, Medical School, University of Athens, Athens, Greece.
National and Kapodistrian University of Athens · GRGeneral Hospital of Athens G. Genimatas · GRHellenic Cooperative Oncology Group · GREvangelismos Hospital · GRUniversity of Pittsburgh · USUPMC Hillman Cancer Center · US

Funding

Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECICH, MICHAEL JOHN · 2008 to 2018
$22.9M
NCI NIH HHS P50 CA121973NCI NIH HHS P50CA121973
6 · The paper itself

Abstract

Adjuvant therapy of stage IIB/III melanoma with interferon reduces relapse and mortality by up to 33% but is accompanied by toxicity-related complications. Polymorphisms of the CTLA-4 gene associated with autoimmune diseases could help in identifying interferon treatment benefits. We previously genotyped 286 melanoma patients and 288 healthy (unrelated) individuals for six CTLA-4 polymorphisms (SNP). Previous analyses found no significant differences between the distributions of CTLA-4 polymorphisms in the melanoma population vs. controls, no significant difference in relapse free and overall survivals among patients and no correlation between autoimmunity and specific alleles. We report new analysis of these CTLA-4 genetic profiles, using Network Phenotyping Strategy (NPS). It is graph-theory based method, analyzing the SNP patterns. Application of NPS on CTLA-4 polymorphism captures allele relationship pattern for every patient into 6-partite mathematical graph P. Graphs P are combined into weighted 6-partite graph S, which subsequently decomposed into reference relationship profiles (RRP). Finally, every individual CTLA-4 genotype pattern is characterized by the graph distances of P from eight identified RRP's. RRP's are subgraphs of S, collecting equally frequent binary allele co-occurrences in all studied loci. If S topology represents the genetic "dominant model", the RRP's and their characteristic frequencies are identical to expectation-maximization derived haplotypes and maximal likelihood estimates of their frequencies. The graph-representation allows showing that patient CTLA-4 haplotypes are uniquely different from the controls by absence of specific SNP combinations. New function-related insight is derived when the 6-partite graph reflects allelic state of CTLA-4. We found that we can use differences between individual P and specific RRPs to identify patient subpopulations with clearly different polymorphic patterns relatively to controls as well as to identify patients with significantly different survival.

Indexed as

Models, BiologicalChemotherapy, AdjuvantGenotypeHaplotypesHumansInterferonsLikelihood FunctionsMelanomaMembrane Transport ProteinsPolymorphism, Single NucleotideSoftwareTranslational Research, BiomedicalInterferonsMembrane Transport ProteinsSLC44A4 protein, human

Identifiers

PMID24475110
PMCPMC3903519
OpenAlexW1996573911

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.