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Bayesian inference of interactions in biological problems.

机译:生物问题相互作用的贝叶斯推断。

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摘要

Recent development of bio-technologies such as microarrays and high-throughput sequencing has greatly accelerated the pace of genetics experimentation and discoveries. As a result, large amounts of high-dimensional genomic data are available in population genetics and medical genetics. With millions of biomarkers, it is a very challenging problem to search for the disease-associated or treatment-associated markers, and infer the complicated interaction (correlation) patterns among these markers.;In this dissertation, I address Bayesian inference of interactions in two biological research areas: whole-genome association studies of common diseases, and HIV drug resistance studies.;For whole-genome association studies, we have developed a Bayesian model for simultaneously inferring haplotype-blocks and selecting SNPs within blocks that are associated with the disease, either individually, or through epistatic interactions with others. Simulation results show that this approach is uniformly more powerful than other epistasis mapping methods. When applied to type 1 diabetes case-control data, we found novel features of interaction patterns in MHC region on chromosome 6.;For HIV drug resistance studies, by probabilistically modeling mutations in the HIV-1 proteases isolated from drug-treated patients, we have derived a statistical procedure that first detects potentially complicated mutation combinations and then infers detailed interacting structures of these mutations.;Finally, the idea of recursively exploring the dependence structure of interactions in the above two research studies can be generalized to infer the structure of Directed Acyclic Graphs. It can be shown that if the generative distribution is DAG-perfect, then asymptotically the algorithm will find the perfect map with probability 1.
机译:诸如微阵列和高通量测序等生物技术的最新发展极大地加快了遗传学实验和发现的步伐。结果,在群体遗传学和医学遗传学中可获得大量的高维基因组数据。拥有数以百万计的生物标志物,寻找与疾病相关或与治疗有关的标志物,并推断这些标志物之间复杂的相互作用(相关性)模式是一个非常具有挑战性的问题。生物学研究领域:常见疾病的全基因组关联研究和HIV耐药性研究;对于全基因组关联研究,我们开发了一种贝叶斯模型,用于同时推断单倍型基因组并在与疾病相关的基因组中选择SNP ,无论是单独还是通过与其他人的上位互动。仿真结果表明,该方法比其他上位制图方法具有更强大的功能。当应用于1型糖尿病病例对照数据时,我们发现了6号染色体MHC区相互作用模式的新特征;对于HIV药物耐药性研究,通过从药物治疗患者中分离出的HIV-1蛋白酶的突变概率模型,我们得出了一种统计方法,该方法首先检测潜在的复杂突变组合,然后推断这些突变的详细相互作用结构。最后,可以将上述两个研究中递归探索相互作用的依赖性结构的思想概括为推断有向结构的结构非循环图。可以证明,如果生成分布是DAG完美的,则渐近算法会找到概率为1的理想映射。

著录项

  • 作者

    Zhang, Jing.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Biology Biostatistics.;Statistics.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 148 p.
  • 总页数 148
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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