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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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Highly correlated gene orthologs between rat and human. The linearized signal (expression level) of the rat gene is plotted versus its ortholog gene in human for the 26 known stimuli. Marker coloring is same as Figure 4; a significant change in expression in rat is marked with a green square and in human with a red circle. The highest MI occurs for a set of ortholog genes that are negatively correlated. I is the MI between the gene orthologs in bits
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btu569-F7: Highly correlated gene orthologs between rat and human. The linearized signal (expression level) of the rat gene is plotted versus its ortholog gene in human for the 26 known stimuli. Marker coloring is same as Figure 4; a significant change in expression in rat is marked with a green square and in human with a red circle. The highest MI occurs for a set of ortholog genes that are negatively correlated. I is the MI between the gene orthologs in bits

Mentions: Figure 7 shows the ortholog pairs with the highest MI. The linearized signal is used to display the expression level of a given gene under a particular stimulus (see Section 2 above). Surprisingly, in agreement with the results from gene set orthologs, the highest MI corresponds to ortholog pairs that are negatively correlated (Rat Gene: 10121 and Human Gene: 16100, DPP4). Here, negative correlation means that when the human gene is over-expressed compared with its control under some stimulus, its rat ortholog is under-expressed compared with its control subject to same stimulus. This suggests that the negative correlation between inter-species gene sets is potentially a consequence of the underlying biology (see Discussion), and not an artifact of the GSEA algorithm.Fig. 7.


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)

Highly correlated gene orthologs between rat and human. The linearized signal (expression level) of the rat gene is plotted versus its ortholog gene in human for the 26 known stimuli. Marker coloring is same as Figure 4; a significant change in expression in rat is marked with a green square and in human with a red circle. The highest MI occurs for a set of ortholog genes that are negatively correlated. I is the MI between the gene orthologs in bits
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325538&req=5

btu569-F7: Highly correlated gene orthologs between rat and human. The linearized signal (expression level) of the rat gene is plotted versus its ortholog gene in human for the 26 known stimuli. Marker coloring is same as Figure 4; a significant change in expression in rat is marked with a green square and in human with a red circle. The highest MI occurs for a set of ortholog genes that are negatively correlated. I is the MI between the gene orthologs in bits
Mentions: Figure 7 shows the ortholog pairs with the highest MI. The linearized signal is used to display the expression level of a given gene under a particular stimulus (see Section 2 above). Surprisingly, in agreement with the results from gene set orthologs, the highest MI corresponds to ortholog pairs that are negatively correlated (Rat Gene: 10121 and Human Gene: 16100, DPP4). Here, negative correlation means that when the human gene is over-expressed compared with its control under some stimulus, its rat ortholog is under-expressed compared with its control subject to same stimulus. This suggests that the negative correlation between inter-species gene sets is potentially a consequence of the underlying biology (see Discussion), and not an artifact of the GSEA algorithm.Fig. 7.

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.

Show MeSH
Related in: MedlinePlus