Double trouble: Predicting new variant counts across two heterogeneous populations.

Collecting genomics data across multiple heterogeneous populations (e.g., across different cancer types) has the potential to improve our understanding of disease. Despite sequencing advances, though, resources often remain a constraint when gathering data. So it would be useful for experimental design if experimenters with access to a pilot study could predict the number of new variants they might expect to find in a follow-up study: both the number of new variants shared between the populations and the total across the populations. While many authors have developed prediction methods for the single-population case, we show that these predictions can fare poorly across multiple populations that are heterogeneous. We prove that, surprisingly, a natural extension of a state-of-the-art single-population predictor to multiple populations fails for fundamental reasons. We provide the first predictor for the number of new shared variants and new total variants that can handle heterogeneity in multiple populations. We show that our proposed method works well empirically using real cancer and population genetics data.

Scaled Process Priors for Bayesian Nonparametric Estimation of the Unseen Genetic Variation.

There is a growing interest in the estimation of the number of unseen features, mostly driven by biological applications. A recent work brought out a peculiar property of the popular completely random measures (CRMs) as prior models in Bayesian nonparametric (BNP) inference for the unseen-features problem: for fixed prior's parameters, they all lead to a Poisson posterior distribution for the number of unseen features, which depends on the sampling information only through the sample size. CRMs are thus not a flexible prior model for the unseen-features problem and, while the Poisson posterior distribution may be appealing for analytical tractability and ease of interpretability, its independence from the sampling information makes the BNP approach a questionable oversimplification, with posterior inferences being completely determined by the estimation of unknown prior's parameters. In this article, we introduce the stable-Beta scaled process (SB-SP) prior, and we show that it allows to enrich the posterior distribution of the number of unseen features arising under CRM priors, while maintaining its analytical tractability and interpretability. That is, the SB-SP prior leads to a negative Binomial posterior distribution, which depends on the sampling information through the sample size and the number of distinct features, with corresponding estimates being simple, linear in the sampling information and computationally efficient. We apply our BNP approach to synthetic data and to real cancer genomic data, showing that: (i) it outperforms the most popular parametric and nonparametric competitors in terms of estimation accuracy; (ii) it provides improved coverage for the estimation with respect to a BNP approach under CRM priors. Supplementary materials for this article are available online.