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'N-of-1-pathways' unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine.

Gardeux V, Achour I, Li J, Maienschein-Cline M, Li H, Pesce L, Parinandi G, Bahroos N, Winn R, Foster I, Garcia JG, Lussier YA - J Am Med Inform Assoc (2014)

Bottom Line: Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations.Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03).The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Bio5 Institute, UA Cancer Center, University of Arizona, Tucson, Arizona, USA Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA Department of Informatics, School of Engineering, EISTI (École Internationale des Sciences du Traitement de l'Information), Cergy-Pontoise, France Institute for Translational Health Informatics, University of Illinois at Chicago, Chicago, Illinois, USA.

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Comparison of the Gene Ontology annotations of Biological Process (GO-BP) terms predicted by N-of-1-pathways in the exploration dataset and their similarity to those of the external gold standard (combination of three validation studies). (A) Global comparison of the 55 patients’ results taken together. Overall, 92% of GO-BP terms of the external gold standard (GS) are found to be predicted by the N-of-1-pathways (0.7<ITS<1 and ITS=1). Conversely, 61% of the predicted and related GO-information theoretic similarity (GO-ITS) overlap with the GS (0.7<ITS<1 and ITS=1) and 10% of GO-BP terms remain unrelated (0.3<ITS) (see online supplementary tables S1 and S2 which provide a subset of results). (B) The level of similarity of individual deregulated mechanisms with the external GS (as a ratio) for each patient. The two diametric extreme prognosis phenotypes show significant differences in their shared GO-BP terms with the GS (in bold) (Wilcoxon test, p=0.03). The two diametric extreme survival phenotypes are annotated: ‘disease-free survival >5 years’ (blue) and ‘death of disease <1 yr’ (red) (figures 4C and 6C).
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AMIAJNL2013002519F5: Comparison of the Gene Ontology annotations of Biological Process (GO-BP) terms predicted by N-of-1-pathways in the exploration dataset and their similarity to those of the external gold standard (combination of three validation studies). (A) Global comparison of the 55 patients’ results taken together. Overall, 92% of GO-BP terms of the external gold standard (GS) are found to be predicted by the N-of-1-pathways (0.7<ITS<1 and ITS=1). Conversely, 61% of the predicted and related GO-information theoretic similarity (GO-ITS) overlap with the GS (0.7<ITS<1 and ITS=1) and 10% of GO-BP terms remain unrelated (0.3<ITS) (see online supplementary tables S1 and S2 which provide a subset of results). (B) The level of similarity of individual deregulated mechanisms with the external GS (as a ratio) for each patient. The two diametric extreme prognosis phenotypes show significant differences in their shared GO-BP terms with the GS (in bold) (Wilcoxon test, p=0.03). The two diametric extreme survival phenotypes are annotated: ‘disease-free survival >5 years’ (blue) and ‘death of disease <1 yr’ (red) (figures 4C and 6C).

Mentions: Since a gold standard (GS) for lung adenocarcinoma does not exist, we generated proxy GSs151718 in order to objectively assess the accuracy of the significantly deregulated mechanisms identified by N-of-1-pathways (see online supplementary methods and figures 2–5).


'N-of-1-pathways' unveils personal deregulated mechanisms from a single pair of RNA-Seq samples: towards precision medicine.

Gardeux V, Achour I, Li J, Maienschein-Cline M, Li H, Pesce L, Parinandi G, Bahroos N, Winn R, Foster I, Garcia JG, Lussier YA - J Am Med Inform Assoc (2014)

Comparison of the Gene Ontology annotations of Biological Process (GO-BP) terms predicted by N-of-1-pathways in the exploration dataset and their similarity to those of the external gold standard (combination of three validation studies). (A) Global comparison of the 55 patients’ results taken together. Overall, 92% of GO-BP terms of the external gold standard (GS) are found to be predicted by the N-of-1-pathways (0.7<ITS<1 and ITS=1). Conversely, 61% of the predicted and related GO-information theoretic similarity (GO-ITS) overlap with the GS (0.7<ITS<1 and ITS=1) and 10% of GO-BP terms remain unrelated (0.3<ITS) (see online supplementary tables S1 and S2 which provide a subset of results). (B) The level of similarity of individual deregulated mechanisms with the external GS (as a ratio) for each patient. The two diametric extreme prognosis phenotypes show significant differences in their shared GO-BP terms with the GS (in bold) (Wilcoxon test, p=0.03). The two diametric extreme survival phenotypes are annotated: ‘disease-free survival >5 years’ (blue) and ‘death of disease <1 yr’ (red) (figures 4C and 6C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215042&req=5

AMIAJNL2013002519F5: Comparison of the Gene Ontology annotations of Biological Process (GO-BP) terms predicted by N-of-1-pathways in the exploration dataset and their similarity to those of the external gold standard (combination of three validation studies). (A) Global comparison of the 55 patients’ results taken together. Overall, 92% of GO-BP terms of the external gold standard (GS) are found to be predicted by the N-of-1-pathways (0.7<ITS<1 and ITS=1). Conversely, 61% of the predicted and related GO-information theoretic similarity (GO-ITS) overlap with the GS (0.7<ITS<1 and ITS=1) and 10% of GO-BP terms remain unrelated (0.3<ITS) (see online supplementary tables S1 and S2 which provide a subset of results). (B) The level of similarity of individual deregulated mechanisms with the external GS (as a ratio) for each patient. The two diametric extreme prognosis phenotypes show significant differences in their shared GO-BP terms with the GS (in bold) (Wilcoxon test, p=0.03). The two diametric extreme survival phenotypes are annotated: ‘disease-free survival >5 years’ (blue) and ‘death of disease <1 yr’ (red) (figures 4C and 6C).
Mentions: Since a gold standard (GS) for lung adenocarcinoma does not exist, we generated proxy GSs151718 in order to objectively assess the accuracy of the significantly deregulated mechanisms identified by N-of-1-pathways (see online supplementary methods and figures 2–5).

Bottom Line: Cross-patient N-of-1-pathways obtains comparable results with conventional genesets enrichment analysis (GSEA) and differentially expressed gene (DEG) enrichment, validated in three external evaluations.Patients were ranked based on the similarity of their deregulated mechanisms to those of an independent gold standard, generating unsupervised clusters of diametric extreme survival phenotypes (p=0.03).The N-of-1-pathways framework provides a robust statistical and relevant biological interpretation of individual disease-free survival that is often overlooked in conventional cross-patient studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Bio5 Institute, UA Cancer Center, University of Arizona, Tucson, Arizona, USA Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA Department of Informatics, School of Engineering, EISTI (École Internationale des Sciences du Traitement de l'Information), Cergy-Pontoise, France Institute for Translational Health Informatics, University of Illinois at Chicago, Chicago, Illinois, USA.

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Related in: MedlinePlus