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Inter-species inference of gene set enrichment in lung epithelial cells from proteomic and large transcriptomic datasets.

Hormoz S, Bhanot G, Biehl M, Bilal E, Meyer P, Norel R, Rhrissorrakrai K, Dayarian A - Bioinformatics (2014)

Bottom Line: Translating findings in rodent models to human models has been a cornerstone of modern biology and drug development.However, in many cases, a naive 'extrapolation' between the two species has not succeeded.In spite of this difference, we were able to develop a robust algorithm to predict gene set activation in NHBE with high accuracy using simple analytical methods.

View Article: PubMed Central - PubMed

Affiliation: Kavli Institute for Theoretical Physics, Kohn Hall, University of California, Santa Barbara, CA 93106, USA, Department of Physics, Department of Molecular Biology and Biochemistry, Busch Campus, Rutgers University, Piscataway, NJ 08854, USA, Johann Bernoulli Institute for Mathematics and Computer Science, University of Groningen, 9700 AK Groningen, The Netherlands and IBM T.J. Watson Research Center, Computational Biology, Yorktown Heights, NY 10003, USA.

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Comparing the correlation between gene sets of human and rat. (A) The rat versus human FDR scores of a given gene set are shown for the 26 stimuli in set A (blue dots). Stimuli with expression levels significantly different from those in control are marked with green squares for rat and red circles for human. When the two markers overlap, that particular stimulus results in a similar response in the two species. The highest MI is surprisingly between gene sets that are negatively correlated. In general, the correlation is lower than the intra-species gene and phosphorylation or the inter-species phosphorylation patterns. The legend above each subplot shows the inter-species MI I and the Pearson correlation coefficient ρ. The gene sets shown are M1017, DNA replication; M852, NFκB activation by TAK1 through phosphorylation and IKKs complex; M940, NFκB activation by TRAF6; M63, osteopontin-mediated events (Subramanian et al., 2005). (B) The first two gene sets, with the additional 26 stimuli of the test set also, shown (triangles). M1017 remains the gene set with the highest inter-species MI through anticorrelation. Although MI is lower, the statistical significance is not diminished
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btu569-F4: Comparing the correlation between gene sets of human and rat. (A) The rat versus human FDR scores of a given gene set are shown for the 26 stimuli in set A (blue dots). Stimuli with expression levels significantly different from those in control are marked with green squares for rat and red circles for human. When the two markers overlap, that particular stimulus results in a similar response in the two species. The highest MI is surprisingly between gene sets that are negatively correlated. In general, the correlation is lower than the intra-species gene and phosphorylation or the inter-species phosphorylation patterns. The legend above each subplot shows the inter-species MI I and the Pearson correlation coefficient ρ. The gene sets shown are M1017, DNA replication; M852, NFκB activation by TAK1 through phosphorylation and IKKs complex; M940, NFκB activation by TRAF6; M63, osteopontin-mediated events (Subramanian et al., 2005). (B) The first two gene sets, with the additional 26 stimuli of the test set also, shown (triangles). M1017 remains the gene set with the highest inter-species MI through anticorrelation. Although MI is lower, the statistical significance is not diminished

Mentions: Figure 4 shows the top four gene set pairs between human and rat with the highest MI. We observed some interesting features in the inter-species correlations among gene sets. First, the computed inter-species gene set MI and correlation coefficients are low compared with their values in inter-species phosphorylation level (Biehl et al., 2014) and intra-species gene–phospho pairs (Dayarian et al., 2014). A concrete manifestation of this discrepancy can be observed in the cumulative number of gene set activations, where the total number of ON events (FDR < 0.25) for the rat gene sets is three times those of the human gene sets for the 26 known stimuli (set A).Fig. 4.


Inter-species inference of gene set enrichment in lung epithelial cells from proteomic and large transcriptomic datasets.

Hormoz S, Bhanot G, Biehl M, Bilal E, Meyer P, Norel R, Rhrissorrakrai K, Dayarian A - Bioinformatics (2014)

Comparing the correlation between gene sets of human and rat. (A) The rat versus human FDR scores of a given gene set are shown for the 26 stimuli in set A (blue dots). Stimuli with expression levels significantly different from those in control are marked with green squares for rat and red circles for human. When the two markers overlap, that particular stimulus results in a similar response in the two species. The highest MI is surprisingly between gene sets that are negatively correlated. In general, the correlation is lower than the intra-species gene and phosphorylation or the inter-species phosphorylation patterns. The legend above each subplot shows the inter-species MI I and the Pearson correlation coefficient ρ. The gene sets shown are M1017, DNA replication; M852, NFκB activation by TAK1 through phosphorylation and IKKs complex; M940, NFκB activation by TRAF6; M63, osteopontin-mediated events (Subramanian et al., 2005). (B) The first two gene sets, with the additional 26 stimuli of the test set also, shown (triangles). M1017 remains the gene set with the highest inter-species MI through anticorrelation. Although MI is lower, the statistical significance is not diminished
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4325538&req=5

btu569-F4: Comparing the correlation between gene sets of human and rat. (A) The rat versus human FDR scores of a given gene set are shown for the 26 stimuli in set A (blue dots). Stimuli with expression levels significantly different from those in control are marked with green squares for rat and red circles for human. When the two markers overlap, that particular stimulus results in a similar response in the two species. The highest MI is surprisingly between gene sets that are negatively correlated. In general, the correlation is lower than the intra-species gene and phosphorylation or the inter-species phosphorylation patterns. The legend above each subplot shows the inter-species MI I and the Pearson correlation coefficient ρ. The gene sets shown are M1017, DNA replication; M852, NFκB activation by TAK1 through phosphorylation and IKKs complex; M940, NFκB activation by TRAF6; M63, osteopontin-mediated events (Subramanian et al., 2005). (B) The first two gene sets, with the additional 26 stimuli of the test set also, shown (triangles). M1017 remains the gene set with the highest inter-species MI through anticorrelation. Although MI is lower, the statistical significance is not diminished
Mentions: Figure 4 shows the top four gene set pairs between human and rat with the highest MI. We observed some interesting features in the inter-species correlations among gene sets. First, the computed inter-species gene set MI and correlation coefficients are low compared with their values in inter-species phosphorylation level (Biehl et al., 2014) and intra-species gene–phospho pairs (Dayarian et al., 2014). A concrete manifestation of this discrepancy can be observed in the cumulative number of gene set activations, where the total number of ON events (FDR < 0.25) for the rat gene sets is three times those of the human gene sets for the 26 known stimuli (set A).Fig. 4.

Bottom Line: Translating findings in rodent models to human models has been a cornerstone of modern biology and drug development.However, in many cases, a naive 'extrapolation' between the two species has not succeeded.In spite of this difference, we were able to develop a robust algorithm to predict gene set activation in NHBE with high accuracy using simple analytical methods.

View Article: PubMed Central - PubMed

Affiliation: Kavli Institute for Theoretical Physics, Kohn Hall, University of California, Santa Barbara, CA 93106, USA, Department of Physics, Department of Molecular Biology and Biochemistry, Busch Campus, Rutgers University, Piscataway, NJ 08854, USA, Johann Bernoulli Institute for Mathematics and Computer Science, University of Groningen, 9700 AK Groningen, The Netherlands and IBM T.J. Watson Research Center, Computational Biology, Yorktown Heights, NY 10003, USA.

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Related in: MedlinePlus