论文标题

比例依赖推断

Scale Reliant Inference

论文作者

Nixon, Michelle Pistner, McGovern, Kyle C., Letourneau, Jeffrey, David, Lawrence A., Lazar, Nicole A., Mukherjee, Sayan, Silverman, Justin D.

论文摘要

许多科学领域,包括人类肠道微生物组科学,收集了多元计数数据,其中计数的总和与所测量的基础系统的规模无关(例如,在受试者的结肠中的总微生物负载)。这种断开连接使下游分析复杂化,例如病例对照研究中的差异分析。本文是由对体外人肠道微生物组模型的新研究进行的。分析这些数据的流行工具导致假阳性和假否定性的速率大大提高。为了了解这些失败,我们提供了正式的问题陈述,该声明构成了这些规模挑战,从经典的可识别性理论角度构成了这些挑战。我们将其称为规模重新推理(SRI)的问题。我们使用此公式来证明SRI对SRI的基本限制,例如一致性和I型误差控制。我们表明,现有方法的失败源于根本无法正确量化系统量表中的不确定性的基本失败。我们证明,一种称为贝叶斯部分鉴定的模型(PIM)的特定类型的贝叶斯模型可以正确量化SRI中的不确定性。我们引入了比例模拟随机变量(SSRV)作为指定和推断贝叶斯PIM的灵活和高效方法。在真实数据和模拟数据的背景下,我们发现SSRV大大降低了I型和II类误差率。

Many scientific fields, including human gut microbiome science, collect multivariate count data where the sum of the counts is unrelated to the scale of the underlying system being measured (e.g., total microbial load in a subject's colon). This disconnect complicates downstream analyses such as differential analysis in case-control studies. This article is motivated by a novel study of in vitro human gut microbiome models. Popular tools for analyzing these data led to dramatically elevated rates of both false positives and false negatives. To understand those failures, we provide a formal problem statement that frames these challenges of scale in terms of the classical theory of identifiability. We call this the problem of Scale Reliant Inference (SRI). We use this formulation to prove fundamental limits on SRI in terms of criteria such as consistency and type-I error control. We show that the failures of existing methods stem from a fundamental failure to properly quantify uncertainty in the system scale. We demonstrate that a particular type of Bayesian model called a Bayesian Partially Identified Model (PIMs) can correctly quantify uncertainty in SRI. We introduce Scale Simulation Random Variables (SSRVs) as a flexible and efficient approach to specifying and inferring Bayesian PIMs. In the context of both real and simulated data, we find SSRVs drastically decrease type-I and type-II error rates.

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