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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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Histogram of the MI for gene set pairs (A) and ortholog genes (B) in bits. (A) The blue dots with error bars are the mean and standard deviation of counts (of 246 gene sets) obtained from computing MI over randomized datasets. The MI of the actual gene sets at 0.24 and 0.32 (refer to Fig. 4) exceeds the values expected by chance at (P < 0.05). (B) Histogram of the MI of ortholog genes (counts are out of 13 841 genes). The ortholog genes do not exhibit a significantly higher MI compared with the gene sets. In fact, because of high number of genes compared with gene sets, it is more likely that high MI in ortholog genes is due to chance
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btu569-F6: Histogram of the MI for gene set pairs (A) and ortholog genes (B) in bits. (A) The blue dots with error bars are the mean and standard deviation of counts (of 246 gene sets) obtained from computing MI over randomized datasets. The MI of the actual gene sets at 0.24 and 0.32 (refer to Fig. 4) exceeds the values expected by chance at (P < 0.05). (B) Histogram of the MI of ortholog genes (counts are out of 13 841 genes). The ortholog genes do not exhibit a significantly higher MI compared with the gene sets. In fact, because of high number of genes compared with gene sets, it is more likely that high MI in ortholog genes is due to chance

Mentions: We computed the statistical significance of the MI of the gene sets by repeating the above analysis on randomized datasets obtained by randomly permuting the stimuli. This generates a distribution for MI expected from chance alone, which can be used to infer the P-value of the measured MI. The top four gene sets shown in Figure 4 were found to be statistically significant (P < 0.05). We find that (Fig. 6A) a MI value < 0.15 bits is no longer statistically significant.Fig. 6.


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)

Histogram of the MI for gene set pairs (A) and ortholog genes (B) in bits. (A) The blue dots with error bars are the mean and standard deviation of counts (of 246 gene sets) obtained from computing MI over randomized datasets. The MI of the actual gene sets at 0.24 and 0.32 (refer to Fig. 4) exceeds the values expected by chance at (P < 0.05). (B) Histogram of the MI of ortholog genes (counts are out of 13 841 genes). The ortholog genes do not exhibit a significantly higher MI compared with the gene sets. In fact, because of high number of genes compared with gene sets, it is more likely that high MI in ortholog genes is due to chance
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

btu569-F6: Histogram of the MI for gene set pairs (A) and ortholog genes (B) in bits. (A) The blue dots with error bars are the mean and standard deviation of counts (of 246 gene sets) obtained from computing MI over randomized datasets. The MI of the actual gene sets at 0.24 and 0.32 (refer to Fig. 4) exceeds the values expected by chance at (P < 0.05). (B) Histogram of the MI of ortholog genes (counts are out of 13 841 genes). The ortholog genes do not exhibit a significantly higher MI compared with the gene sets. In fact, because of high number of genes compared with gene sets, it is more likely that high MI in ortholog genes is due to chance
Mentions: We computed the statistical significance of the MI of the gene sets by repeating the above analysis on randomized datasets obtained by randomly permuting the stimuli. This generates a distribution for MI expected from chance alone, which can be used to infer the P-value of the measured MI. The top four gene sets shown in Figure 4 were found to be statistically significant (P < 0.05). We find that (Fig. 6A) a MI value < 0.15 bits is no longer statistically significant.Fig. 6.

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