Zhang Jinghui, Rowe William L, Struewing Jeffery P, Buetow Kenneth H
Laboratory of Population Genetics, National Cancer Institute/National Institutes of Health, 8424 Helgerman Court, Room 101, MSC 8302, Bethesda, MD 20892-8302, USA.
Nucleic Acids Res. 2002 Dec 1;30(23):5213-21. doi: 10.1093/nar/gkf654.
We have developed a software analysis package, HapScope, which includes a comprehensive analysis pipeline and a sophisticated visualization tool for analyzing functionally annotated haplotypes. The HapScope analysis pipeline supports: (i) computational haplotype construction with an expectation-maximization or Bayesian statistical algorithm; (ii) SNP classification by protein coding change, homology to model organisms or putative regulatory regions; and (iii) minimum SNP subset selection by either a Brute Force Algorithm or a Greedy Partition Algorithm. The HapScope viewer displays genomic structure with haplotype information in an integrated environment, providing eight alternative views for assessing genetic and functional correlation. It has a user-friendly interface for: (i) haplotype block visualization; (ii) SNP subset selection; (iii) haplotype consolidation with subset SNP markers; (iv) incorporation of both experimentally determined haplotypes and computational results; and (v) data export for additional analysis. Comparison of haplotypes constructed by the statistical algorithms with those determined experimentally shows variation in haplotype prediction accuracies in genomic regions with different levels of nucleotide diversity. We have applied HapScope in analyzing haplotypes for candidate genes and genomic regions with extensive SNP and genotype data. We envision that the systematic approach of integrating functional genomic analysis with population haplotypes, supported by HapScope, will greatly facilitate current genetic disease research.
我们开发了一个软件分析包HapScope，它包括一个用于分析功能注释单倍型的综合分析流程和一个复杂的可视化工具。HapScope分析流程支持：(i) 使用期望最大化或贝叶斯统计算法进行计算单倍型构建；(ii) 通过蛋白质编码变化、与模式生物的同源性或假定调控区域进行单核苷酸多态性（SNP）分类；以及(iii) 通过暴力算法或贪婪划分算法选择最小SNP子集。HapScope查看器在一个集成环境中显示带有单倍型信息的基因组结构，提供八种可供选择的视图来评估遗传和功能相关性。它具有一个用户友好的界面，用于：(i) 单倍型块可视化；(ii) SNP子集选择；(iii) 用子集SNP标记进行单倍型合并；(iv) 纳入实验确定的单倍型和计算结果；以及(v) 数据导出以进行进一步分析。将统计算法构建的单倍型与实验确定的单倍型进行比较，结果显示在具有不同核苷酸多样性水平的基因组区域中，单倍型预测准确性存在差异。我们已将HapScope应用于分析具有大量SNP和基因型数据的候选基因和基因组区域的单倍型。我们设想，在HapScope支持下，将功能基因组分析与群体单倍型相结合的系统方法将极大地促进当前的遗传疾病研究。
