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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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8.5 Target Prediction Ensemble Analysis Results<br />

query were to start from a list containing g = 30 genes and n = 3 prediction<br />

algorithms were selected, then the Cumulative filter would range from one to<br />

30x3 = 90 and setting it on 56 would cause it to report only those microRNAs<br />

that target 56 genes as predicted by any combination <strong>of</strong> the prediction algo-<br />

rithms (Fig 8.3).<br />

While the Minimum and Cumulative filters operate on microRNAs, the possi-<br />

bility <strong>of</strong> selecting a subset <strong>of</strong> the eight prediction algorithms affords the user<br />

control over the number <strong>of</strong> algorithms required to report a given prediction,<br />

and thus define the criteria by which predictions are deemed accurate. For<br />

example, certain applications - such as experimental validation and cloning <strong>of</strong><br />

microRNAs involved in particular pathways <strong>of</strong> interest - involve a significant<br />

amount <strong>of</strong> effort to perform. If this is the ultimate goal <strong>of</strong> the investigation,<br />

then it is desirable to focus on a small set <strong>of</strong> highly-scoring microRNA targets<br />

unanimously reported by several algorithms. Other searches though, such as<br />

those performed for comparative genomic analyses, are limited only by com-<br />

putational feasibility and can therefore afford to include a greater number <strong>of</strong><br />

putative regulators whose involvement may only be predicted by one or two<br />

algorithms.<br />

Any combination <strong>of</strong> the above filtering methods is possible, keeping in mind<br />

that: (i) they are always applied to the original set <strong>of</strong> data, and that (ii) a<br />

given gene is included in the final results only if it passes the criteria imposed<br />

by each individual filter set by the user. Therefore, the utility <strong>of</strong> applying dif-<br />

ferent filter combinations depends on the relevance <strong>of</strong> the biological question<br />

they help to answer.<br />

8.5 Target Prediction Ensemble Analysis<br />

A question we wanted to ask was whether any prediction algorithm fared bet-<br />

ter than any other combination <strong>of</strong> prediction algorithms. Since the divergence<br />

between prediction results from any algorithm is large, finding whether any<br />

combination <strong>of</strong> a subset <strong>of</strong> these algorithms fares better than any algorithm<br />

alone, is a necessary step. Using our s<strong>of</strong>tware tool GenemiR we tried to eluci-<br />

date how different combinations <strong>of</strong> prediction algorithms fared with respect to<br />

the single algorithm, and thus address the hypothesis suggested by Alexiou et<br />

al [16] that combinations <strong>of</strong> algorithms predict more accurately than the single<br />

algorithm alone. The way we addressed this problem was using relevant ex-<br />

perimental data from exon arrays and microRNA microarrays generated from<br />

211

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