利用稀释实验和深度病毒测序量化HIV病毒库
Quantifying the HIV reservoir with dilution assays and deep viral sequencing
AI总结：
本文提出结合QVOA稀释实验与UDSA深度病毒测序数据的统计方法，用于在部分测序数据缺失、灵敏度和特异性不完美及小样本情况下更准确地估计HIV病毒库大小（IUPM），并已在R包SLDeepAssay中实现。
摘要：
接受抗逆转录病毒治疗的人类免疫缺陷病毒（HIV）感染者，通过标准检测方法通常检测不到病毒水平，但“潜伏”的HIV仍持续存在于病毒库中。清除这些病毒库是HIV治愈研究的目标。定量病毒生长实验（QVOA）常用于估计病毒库大小，即HIV持续存在的静息CD4+ T细胞中每百万细胞的感染单位数（IUPM）。最近开发了QVOA的一种新变体，即生长病毒的Ultra Deep Sequencing Assay（UDSA，超深度测序实验），可进一步量化受感染孔子集内的病毒谱系数量。对孔的子集执行UDSA可提供额外信息，从而改善IUPM估计。本文考虑了结合稀释实验（QVOA）和深度病毒测序（UDSA）数据对IUPM进行统计推断的问题，即使部分深度测序数据缺失。提出了可适应在多个稀释水平下测序的孔以及灵敏度和特异性不完美的实验的方法，并包含一种针对小样本的新型偏差校正估计量。所提出的方法在模拟研究中进行了评估，应用于北卡罗来纳大学HIV治愈中心的数据，并在开源R包SLDeepAssay中实现。
英文摘要：
People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative viral outgrowth assay (QVOA) is commonly used to estimate the reservoir size, i.e., the infectious units per million (IUPM) of HIV-persistent resting CD4+ T cells. A new variation of the QVOA, the Ultra Deep Sequencing Assay of the outgrowth virus (UDSA), was recently developed that further quantifies the number of viral lineages within a subset of infected wells. Performing the UDSA on a subset of wells provides additional information that can improve IUPM estimation. This paper considers statistical inference about the IUPM from combined dilution assay (QVOA) and deep viral sequencing (UDSA) data, even when some deep sequencing data are missing. Methods are proposed to accommodate assays with wells sequenced at multiple dilution levels and with imperfect sensitivity and specificity, and a novel bias-corrected estimator is included for small samples. The proposed methods are evaluated in a simulation study, applied to data from the University of North Carolina HIV Cure Center, and implemented in the open-source R package SLDeepAssay.
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