On the Analysis of Optical Mapping Data - University of Wisconsin ...
On the Analysis of Optical Mapping Data - University of Wisconsin ...
On the Analysis of Optical Mapping Data - University of Wisconsin ...
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65<br />
and rate parameters<br />
Λ i = E(N i ) =<br />
Λ 0i<br />
∫ bi<br />
a i<br />
∫ bi<br />
= κ λ 0 (t) dt<br />
a i<br />
λ(t) dt<br />
In terms <strong>of</strong> <strong>the</strong>se parameters, lack <strong>of</strong> CNP in G i corresponds to <strong>the</strong> null hypo<strong>the</strong>sis H i : Λ i =<br />
Λ 0i . N i ∼ Poisson (Λ 0i ) under H i , forming <strong>the</strong> basis for a test for each H i . Under departures<br />
from H i , N i ∼ Poisson (Λ i ), with power given by<br />
β(Λ i |Λ 0i ) = P Λi (H i rejected)<br />
Figure 4.1 shows that <strong>the</strong> power to detect a given copy number change depends on <strong>the</strong><br />
choice <strong>of</strong> Λ 0i , providing us a prescription for <strong>the</strong> choice <strong>of</strong> <strong>the</strong> intervals G i . Specifically, to<br />
obtain tests with a common desired power, obtain <strong>the</strong> corresponding value <strong>of</strong> Λ 0 and choose<br />
G i = (a i , b i ] so that Λ 0i = Λ 0 . In o<strong>the</strong>r words, <strong>the</strong> intervals are chosen to have constant<br />
expected counts under <strong>the</strong> null <strong>of</strong> no CNP. The non-homogeneity <strong>of</strong> λ 0 implies that <strong>the</strong><br />
G i ’s have variable length. The choice <strong>of</strong> Λ 0 , <strong>the</strong> expected number <strong>of</strong> Y i ∈ G i under <strong>the</strong><br />
null, represents a trade-<strong>of</strong>f that is fairly intuitive, namely, <strong>the</strong> more data (number <strong>of</strong> aligned<br />
optical maps) we have, <strong>the</strong> shorter <strong>the</strong> intervals and hence higher <strong>the</strong> resolution with which<br />
we can detect copy number changes with a given power. An implicit assumption here is that<br />
copy number does not change within an interval. Long intervals give more power to detect<br />
CNP, but only if <strong>the</strong> alteration holds throughout <strong>the</strong> interval.<br />
Negative binomial: To determine intervals G i that all have Λ 0 expected hits under H i ,<br />
we need to know λ 0 (·). In practice, we only have control data {X k } that are event times <strong>of</strong><br />
one realization <strong>of</strong> a NHPP with intensity λ 0 (·). To address <strong>the</strong> problem, define quantities<br />
M i = ∑ k I {a i