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Correction: A Likelihood Approach to Estimate the Number of Co-Infections

  • Kristan A. Schneider,
  • Ananias A. Escalante

The authors wish to acknowledge an error that was overseen in the proof of Result 1 in [1]. By carefully inspecting the authors’ proof, it becomes clear that an MLE cannot exist if Nk = N for at least one k. This is easily seen from the authors’ formula for in Result 1, where Nk = N implies , a contradiction since then . All results however remain valid as stated if their Assumption 1 is replaced by the following version.

Assumption 1 Assume that the sum over the lineages’ prevalences is larger than one, but no alleles is 100% prevalent. In other words, more than one lineage is found in at least one infection, i.e., and all lineages are not found in every infection, i.e., NkN for all k.

By replacing Assumption 1 with the version above in [1], the results hold without modifications. All other modifications that need to be made in the article are minor and obvious. However, the case Nk = N for at least one k was not properly addressed. This occurred because it was overseen that the proof of in Result 1 is not applicable then. What goes wrong in this case? The answer is somewhat subtle. Heuristically, this contradiction occurs because no point in the parameter space is a critical point, i.e., a point at which all derivatives of L vanish. However, for any fixed λ, L(λ, p|x) attains a maximum for some , with . The reason is that L(λ, p|x) = −∞ for (where denotes the n−1-dimensional simplex). For λ → 0, . Hence, is necessarily monotonically increasing in λ, implying that no MLE exists. In mathematical terms this can be formulated as follows:

Remark 1 Assume that at least one lineage is found in every sample, i.e.,Nk = N for at least one k, but not all are found in every sample, i.e.,NkN for at least one j. Then, the log-likelihood function does not attain a maximum. However, its smallest upper bound is

The supremum is reached in the limit of any sequence (λt, pt) with , if NkN and if Nk = N.

Proof. Because L(λ, p|x) is bounded by 0, the supremum exists. Furthermore, a sequence (λt, pt) exists with .

Without loss of generality let N1,…,Nm < N and Nm+1 = … = Nn = N. Hence, (1)

Let (λt) be any monotone sequence with . Moreover, let ck >0 for k = 1,…,m. Now let pt be a sequence satisfying for k = 1,…,m and for k = m + 1,…,n. Without loss of generality let for k = 1,…,m and for k = m + 1,…,n. For sufficiently large t this sequence is defined and . Hence,

Next define . Note that this definition is independent of the sequence (λt, pt), with λtpt →(c1,…,cm, ∞,…,∞) for t → ∞.

The next aim, is to identify potential maxima of f. Clearly, . Equating the partial derivatives to zero gives . The Hessian matrix is given by and clearly negative definite. Thus, f attains a global maximum at . Therefore .

If (λt, pt) is any sequence with for a k with 1 ≤ km, it is easily seen from (1) that . Moreover, if for 1 ≤ km and at least one k with m + 1 ≤ kn, without loss of generality for , (1) implies implying that this limit is less than the maximum of f. The above considerations imply that the supremum of the log-likelihood function must be the maximum of f. Deriving finishes the proof.

The case that Nk = N for all k is treated in [1]. Moreover, obviously in Remark 1 of [1] a misprint occurred. The expression needs to be replaced by , while the same expression needs to be replaced by in the paragraph below Result 2.

Reference

  1. 1. Schneider KA, Escalante AA (2014) A Likelihood Approach to Estimate the Number of Co-Infections. PLoS ONE 9(7): e97899. https://doi.org/10.1371/journal.pone.0097899 pmid:24988302