ArticleBMC bioinformatics2009
Mechanism-anchored profiling derived from epigenetic networks predicts outcome in acute lymphoblastic leukemia.
Article in BMC bioinformatics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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.
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Who cites it
4 citing papers in PubMed, 11 citations in OpenAlex.
- Identification of epigenetic modifications that contribute to pathogenesis in therapy-related AML: Effective integration of genome-wide histone modification with transcriptional profiles.BMC medical genomics · 2015Article
- Connecting the dots in translational bioinformatics: TBC 2014 collection.BMC medical genomics · 2015Article
- COPD Hospitalization Risk Increased with Distinct Patterns of Multiple Systems Comorbidities Unveiled by Network Modeling.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2014Article
- Selected proceedings of the 2009 Summit on Translational Bioinformatics.BMC bioinformatics · 2009Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCurrent outcome predictors based on "molecular profiling" rely on gene lists selected without consideration for their molecular mechanisms. This study was designed to demonstrate that we could learn about genes related to a specific mechanism and further use this knowledge to predict outcome in patients - a paradigm shift towards accurate "mechanism-anchored profiling". We propose a novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network associated to epigenetic regulation consisting of phenotypes, genes and mechanisms. Genes termed as GEMs in this network meet all of the following criteria: (i) they are co-expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype.
resultsThis proof-of-concept study, which focuses on epigenetic mechanisms, was conducted in a well-studied set of 132 acute lymphoblastic leukemia (ALL) microarrays annotated with nine distinct phenotypes and three measures of response to therapy. We used established parametric and non parametric statistics to derive the PGnet tripartite network that consisted of 10 phenotypes and 33 significant clusters of GEMs comprising 535 distinct genes. The significance of PGnet was estimated from empirical p-values, and a robust subnetwork derived from ALL outcome data was produced by repeated random sampling. The evaluation of derived robust network to predict outcome (relapse of ALL) was significant (p = 3%), using one hundred three-fold cross-validations and the shrunken centroids classifier.
conclusionTo our knowledge, this is the first method predicting co-expression networks of genes associated with epigenetic mechanisms and to demonstrate its inherent capability to predict therapeutic outcome. This PGnet approach can be applied to any regulatory mechanisms including transcriptional or microRNA regulation in order to derive predictive molecular profiles that are mechanistically anchored. The implementation of PGnet in R is freely available at http://Lussierlab.org/publication/PGnet.
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Registered trials
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.