功能成分预测因子的对数对比回归：早产儿肠道微生物组轨迹与神经行为结果的联系
Log-Contrast Regression with Functional Compositional Predictors: Linking Preterm Infant's Gut Microbiome Trajectories to Neurobehavioral Outcome
摘要：
新生儿重症监护室（NICU）的经验是众所周知的驱动早产儿的神经发育和健康结果的最关键的因素之一。据推测，极早产儿的应激早期生活经历是通过所谓的脑-肠轴的调节来印记肠道微生物组，因此，某些微生物组标志物可预测后期婴儿神经发育。为了研究，进行了一项早产儿研究;在婴儿出生后第一个月收集婴儿粪便样本，得到功能性组成微生物组数据，并在婴儿达到月经后36-38周时测量神经行为结果。为了识别潜在的微生物组标志物并估计出生后早期肠道微生物组组成的轨迹如何影响早产儿后期的神经行为结果，我们创新了具有功能组成预测因子的稀疏对数对比回归。函数的单纯形结构被严格保留，并且函数的组成预测因子被允许具有稀疏的、平滑变化的和累积的对结果的影响。通过一个务实的基础扩展步骤，问题归结为一个线性约束稀疏组回归，我们开发了一个有效的算法，并获得理论性能保证。我们的方法在早产儿研究中产生了有见地的结果。确定的微生物组标志物及其对神经行为结果影响的估计时间动态揭示了出生后早期阶段的压力积累与婴儿神经发育过程之间的联系。
英文摘要：
The neonatal intensive care unit (NICU) experience is known to be one of the most crucial factors that drive preterm infant's neurodevelopmental and health outcomes. It is hypothesized that stressful early life experience of very preterm neonate is imprinting gut microbiome by the regulation of the so-called brain-gut axis, and consequently, certain microbiome markers are predictive of later infant neurodevelopment. To investigate, a preterm infant study was conducted; infant fecal samples were collected during the infants' first month of postnatal age, resulting in functional compositional microbiome data, and neurobehavioral outcomes were measured when infants reached 36-38 weeks of post-menstrual age. To identify potential microbiome markers and estimate how the trajectories of gut microbiome compositions during early postnatal stage impact later neurobehavioral outcomes of the preterm infants, we innovate a sparse log-contrast regression with functional compositional predictors. The functional simplex structure is strictly preserved, and the functional compositional predictors are allowed to have sparse, smoothly varying, and accumulating effects on the outcome through time. Through a pragmatic basis expansion step, the problem boils down to a linearly constrained sparse group regression, for which we develop an efficient algorithm and obtain theoretical performance guarantees. Our approach yields insightful results in the preterm infant study. The identified microbiome markers and the estimated time dynamics of their impact on the neurobehavioral outcome shed light on the linkage between stress accumulation in early postnatal stage and neurodevelopmental process of infants.
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