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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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8.5 Target Prediction Ensemble Analysis Results<br />

summarised in figure 8.4. We first run the method on the predictions from<br />

each algorithm alone and then extended it to all combinations <strong>of</strong> prediction<br />

algorithm results. The score E reflecting the accuracy <strong>of</strong> each prediction or<br />

combination <strong>of</strong> predictions, ranges between 0 and 1 (0 > E > 1), with 1 re-<br />

flecting a perfectly matching set <strong>of</strong> predictions between the algorithm being<br />

evaluated and our experimental data. The score is calculated following these<br />

successive steps:<br />

1. filter out, for each prediction algorithm and for each microRNA exper-<br />

imentally observed to be up-regulated, the genes that are predicted to<br />

be target by that microRNA but are not present in the gene background<br />

list;<br />

2. generate a union list from the genes filtered in step 1 for the entire cohort<br />

<strong>of</strong> up-regulated microRNAs, for each prediction algorithm;<br />

3. iterate over each gene in the union list and increase a cumulative counter<br />

every time the gene is predicted to be targeted by one <strong>of</strong> the up-regulated<br />

microRNAs, for each prediction algorithm. This counter is normalised<br />

to the number <strong>of</strong> microRNAs that the prediction contains from the list<br />

<strong>of</strong> 258 experimentally measured microRNAs;<br />

4. sort the union gene list by the count calculated in step 3 to generate a<br />

"hit" list, representative <strong>of</strong> each prediction algorithm;<br />

5. iterate over the hit list summing in a cumulative counter C1, the counts<br />

associated to all the genes in the list, which have been predicted by the<br />

prediction algorithm ;<br />

6. iterate over the hit list summing in a cumulative counter C2, the counts<br />

associated to the genes that are experimentally observed to be down-<br />

regulated in our exon array data;<br />

7. generate a score value by dividing the cumulative counters C1 and C2,<br />

representing a measure <strong>of</strong> how well a prediction algorithm fared based<br />

on how many genes it correctly predicted to be targeted in our GNS cell<br />

lines, considering the same cell line expression pr<strong>of</strong>ile as a background<br />

for calculations.<br />

Scores for each single prediction algorithm are listed in table 8.2 below. To<br />

evaluate whether combinations <strong>of</strong> different algorithms were more accurate at<br />

213

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