Wu Song, Yang Jie, Wu Rongling
Department of Statistics, University of Florida, Gainesville, FL 32611, USA.
Bioinformatics. 2007 Jul 1;23(13):i569-76. doi: 10.1093/bioinformatics/btm164.
Functional mapping has proven to be powerful for characterizing quantitative trait loci (QTL) that control complex dynamic traits. More recently, functional mapping has been extended to identify the host QTL responsible for HIV dynamics by incorporating a parametric bi-exponential function for earlier stages of viral load trajectories. However, existing functional mapping cannot be used to map long-term HIV dynamics because no mathematical functions are available for later stages of HIV dynamic changes.
We derived a statistical model for functional mapping of dynamic QTL through characterizing HIV load trajectories during a long-term period semiparametrically. The new model was constructed within the maximum likelihood framework and implemented with the EM-simplex algorithm. It allows for the test of differences in the genetic control of short- and long-term HIV dynamics and the characterization of the effects of viral-host genome interaction. Extensive simulation studies have been performed to test the statistical behavior of this model. The new model will provide an important tool for genetic and genomic studies of human complex diseases like HIV/AIDS and their pathological progression.
Available on request from the corresponding author.
功能图谱已被证明在表征控制复杂动态性状的数量性状基因座（QTL）方面很强大。最近，通过纳入病毒载量轨迹早期阶段的参数双指数函数，功能图谱已扩展到识别负责HIV动态变化的宿主QTL。然而，现有的功能图谱不能用于绘制长期HIV动态变化，因为没有适用于HIV动态变化后期阶段的数学函数。
我们通过半参数化表征长期HIV载量轨迹，推导了一个用于动态QTL功能图谱的统计模型。新模型在最大似然框架内构建，并通过EM - 单纯形算法实现。它允许测试短期和长期HIV动态变化的遗传控制差异，并表征病毒 - 宿主基因组相互作用的影响。已进行了广泛的模拟研究来测试该模型的统计行为。新模型将为HIV/AIDS等人类复杂疾病及其病理进展的遗传和基因组研究提供重要工具。
可应通讯作者要求提供。
