IMSLS_LAMBDAS, int n_lamdas, float lambdas[] (Input) An array of length n_lambdas containing the grid values on [0,1) used in the estimate of the null probability.
IMSLS_GAMMA_PARAM, float gamma (Input) Size of the rejection region (0 ≤gamma≤ 1.0) used in the calculation of the FDR and pFDR measures.
Default: gamma = 0.05
IMSLS_METHOD, int method (Input) Specifies the method used to remove the dependence of the null probability estimate on the lambda variable. method = 1 or method = 0: when method = 0, a bootstrap with n_samples is used; when method = 1, a cubic spline smoother is used.
Default: method = 0
IMSLS_SMOOTHING_PAR, float smoothing_par (Input) Smoothing parameter (0 ≤smoothing_par≤ 1.0) argument for the cubic spline smoother. Only used if method = 1.
Default: If method = 1 and this optional argument is not provided, the smoothing parameter is selected by cross‑validation.
IMSLS_N_SAMPLE, intn_samples (Input) Number of bootstrap samples to make for method = 0 or when estimating upper confidence limits when IMSLS_CONFIDENCE is present.
Default: n_samples = 100.
IMSLS_RANDOM_SEED, intrandom_seed (Input) The seed of the random number generator used in generating the bootstrap samples. If random_seed is 0, a value is computed using the system clock; hence, the results may be different between different calls with the same inputs.
IMSLS_NULL_PROB, float*pi0 (Output) The null probability estimate.
IMSLS_UPPER_LIMITS, float**upper_limits (Output) Address of a pointer to an array of length 2 containing the (confid)% upper bounds for pFDR and FDR.
IMSLS_UPPER_LIMITS_USER, float upper_limits[] (Output) Storage for array upper_limits is supplied by the user. See IMSLS_UPPER_LIMITS.
IMSLS_RETURN_USER, float qvalues[] (Output) Storage for the return value is supplied by the user.
Description
Let {p1, p2, ..., pm}be the p‑values associated with m independent tests of a statistical hypothesis. The following table summarizes the possible outcomes of the m tests. Note that the only known quantities in the table are W, R, and, m.
Hypothesis
Accept
Reject
Total
Null is true
U
V
m0
Alternative is true
T
S
m1
Total
W
R
m
In the above table, V is the number of false discoveries (and the number of type I errors). Whereas the type I error rate is the probability of rejecting at least one true null hypothesis, the false discovery rate (FDR) (Benjamini and Hochberg (1995)), is the expected proportion of falsely rejected true nulls. In other words, the FDR is the expected proportion of “false positives” among the tests that are deemed significant. Using the notations from the table,
The denominator R∨ 1 = max(R,1) avoids division by 0 in case there are no significant results (R = 0). The positive false discovery rate, or pFDR, defined in Storey (2001), is conditional on there being at least one significant test (R > 0):
From Theorem 1 in Storey (2001),
where π0 is the probability that an individual hypothesis is null, and Pr[P ≤γ∣H = 0] = γ is the probability an individual hypothesis is rejected given that it is null. The parameter γ is the predefined size of the rejection region. The denominator is the probability that a test is rejected, given γ. This relationship arises from Baye’s Theorem and the assumption that the p‑values are independent.
An estimator for m0, the number of true null hypotheses is
where λ is a significance level on the interval [0,1) and W(λ) is the number of tests that are accepted at level λ That is, W(λ) = #{ pi > λ}. An estimator for the probability of a null hypothesis π0 is then:
The parameter λ is a tuning parameter used to estimate the true null distribution. The rationale is that the p-values of the null hypotheses are uniformly distributed and most of the larger p‑values ( >λ) will be from the null distribution. See Storey and Tibshirani ( 2003) for further details.
Now using
Storey (2002) gives the following estimators for pFDR and FDR:
and
Note that 1‑(1 ‑γ)m is a lower bound for , the probability of at least one significant test, and
is a conservative estimate for the type I error, given that R > 0.
In imsls_f_false_discovery_rates, the estimates above are calculated on a grid of λ values on [0,1) and the minimizer is noted. The calculations are then repeated on B bootstrap samples of the p‑values. The dependence on λ is removed by one of two methods. In Algorithm 3 of Storey (2002), minimizes the mean squared error between the bootstrap estimates and the original minimum of the estimates over the grid of λ values. Then, . A second method, suggested by Storey and Tibshirani (2003), uses a cubic spline smoother on the set of values, . Then the smoothed value . Upper confidence bounds are determined by taking the (1 ‑α) quantile of the bootstrapped pFDR and FDR values, using the smoothed value obtained by either method above.
The q‑value, introduced in Storey (2001), is the pFDR analogue of the p‑value. For independent tests, the q‑value of the observed p‑value is
Whereas a p‑value is the minimum type I error rate that can occur while rejecting a test with a given value of the test statistic, the q‑value is the minimum pFDR that can occur while still rejecting the test. For more details see Storey (2001) and Storey (2002). To find the q‑values, imsls_f_false_discovery_rates implements the algorithm given in Storey and Tibshirani (2003).
Examples
Example 1
The p‑values are 20 independent realizations of a uniform (0,1) random variable. The null-probability estimate, q‑values, and upper confidence limits are returned.
This example applies the cubic spline smoothing method to get an estimate of the null probability. Note that the p‑values are the same as in Example 1, but the null probability estimate is larger in this case.
