Highly active enhancer regions are thought to be important for the cell fate (Andersson et al. 2014, FANTOM5 consortium, Hnisz et al. 2013). Highly active enhancers regions have been selected in GM12878 cells. Similarity of ChIP-seq profiles has been tested using two histone post-transcriptional modifications linked to highly active enhancers H3K27ac (DCC accession: ENCFF000ASG) and H3K4me1 (DCC accession: ENCFF000ARY) from the Encyclopedia of DNA Elements (ENCODE) data (Dunham I et al. 2012). Accordingly with the literature, similarity between the profiles of these two histone marks has been identified.
First, the similaRpeak
package must be loaded.
library(similaRpeak)
A region, chr7:61968807-61969730, shows interesting profiles for both histones. Let's load the data for this region.
data(chr7Profiles) str(chr7Profiles)
H3K27ac and H3K4me1 profiles have those shapes:
plot(chr7Profiles$chr7.61968807.61969730$H3K27ac, type="l", col="blue", xlab="", ylab="", ylim=c(0, 700), main="chr7:61968807-61969730") par(new=TRUE) plot(chr7Profiles$chr7.61968807.61969730$H3K4me1, type="l", col="darkgreen", xlab="Position", ylab="Reads per million (RPM)", ylim=c(0, 700)) legend("topleft", c("H3K27ac","H3K4me1"), cex=1.2, col=c("blue","darkgreen"), lty=1)
Figure S8. H3K27ac profile versus H3K4me1 profile
The metrics are calculated using the similarity
function which takes as
arguments the two ChIP-Seq profiles vectors and the threshold values.
metrics <- similarity(chr7Profiles$chr7.61968807.61969730$H3K27ac, chr7Profiles$chr7.61968807.61969730$H3K4me1, ratioAreaThreshold=5, ratioMaxMaxThreshold=2, ratioIntersectThreshold=5, ratioNormalizedIntersectThreshold=2, diffPosMaxThresholdMinValue=10, diffPosMaxThresholdMaxDiff=100, diffPosMaxTolerance=0.01)
The similarity
function returns a list which contains the general
information about both ChIP-Seq profiles and a list of all calculated metrics.
metrics
Each specific information can be directly accessed. Some examples:
metrics$areaProfile1 metrics$areaProfile2 metrics$metrics$RATIO_INTERSECT
The RATIO_INTERSECT value of r round(metrics$metrics$RATIO_INTERSECT, 2)
and the RATIO_MAX_MAX value of r round(metrics$metrics$RATIO_MAX_MAX, 2)
are quite low. Both values can be explained by the large difference in
coverage between profiles. Those values could be interpreted as two profiles
with low level of similarity. However, the RATIO_NORMALIZED_INTERSECT of
r round(metrics$metrics$RATIO_NORMALIZED_INTERSECT, 2)
is much closer to 1.
It could be a sign that the profiles, once normalized, are quite similar.
This hypothesis can be validated by looking at a graph of the normalized
profiles :
plot(chr7Profiles$chr7.61968807.61969730$H3K27ac* length(chr7Profiles$chr7.61968807.61969730$H3K27ac)/ sum(chr7Profiles$chr7.61968807.61969730$H3K27ac, na.rm=TRUE), type="l", col="blue", xlab="", ylab="", ylim=c(0, 3.5)) par(new=TRUE) plot(chr7Profiles$chr7.61968807.61969730$H3K4me1* length(chr7Profiles$chr7.61968807.61969730$H3K4me1)/ sum(chr7Profiles$chr7.61968807.61969730$H3K4me1, na.rm=TRUE), type="l", col="darkgreen", xlab="Position", ylab="Normalized Coverage (Coverage/Mean Coverage)", ylim=c(0, 3.5)) legend("topleft", c("H3K27ac","H3K4me1"), cex=1.2, col=c("blue","darkgreen"), lty=1)
Figure S9. Normalized H3K27ac profile versus normlized H3K4me1 profile
Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, et al. (2014) An atlas of active enhancers across human cell types and tissues. Nature, 507(7493), 455-461.
Dunham I, Kundaje A, Aldred SF, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012 Sep 6;489(7414):57-74.
Forrest AR, Kawaji H, Rehli M, Baillie JK, de Hoon MJ, et al. (2014) A promoter-level mammalian expression atlas. Nature, 507(7493):462-470.
Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, et al. (2013) Super-enhancers in the control of cell identity and disease. Cell, 155(4), 934-947.
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