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    • 5. 发明授权
    • Method for alignment of DNA sequences with enhanced accuracy and read length
    • DNA序列比对准确性和读取长度的方法
    • US06760668B1
    • 2004-07-06
    • US09536111
    • 2000-03-24
    • Alexandre IzmailovHenryk ZaleskiStephen Darasch
    • Alexandre IzmailovHenryk ZaleskiStephen Darasch
    • G06F1900
    • G06F19/22
    • In order to align DNA sequence data traces, an experimental data trace representing the positions of a first species of base within a target polynucleotide and a reference data trace representing the positions of a second species of base (which may be the same as or different from the first species) within a reference polynucleotide are obtained by separating appropriate sequencing fragments generated from the target and reference polynucleotides on an electrophoresis gel. For each reference data trace, a plurality of peaks corresponding to fragments having a size in the range of 40 to 1200 bases are selected. A base number is assigned to each of the selected peaks in the reference data trace, and a numerical “peak file” is created with information about the peak number and migration time (or distance). This peak file is analyzed to determine a set of polynomial coefficients which will allow substantial linearization of a plot of peak number versus separation between adjacent peaks and alignment of the traces with respect to each other. These coefficients are used to create a corrected time scale identifying where peaks should be located on a given experimental gel. This corrected time scale is used to guide the sampling of the experimental data, and for assignment of peaks within the data.
    • 为了校准DNA序列数据迹线,表示靶多核苷酸中第一种碱基的位置的实验数据迹线和表示第二种碱基的位置的参考数据迹线(其可以相同或不同于 通过在电泳凝胶上分离从靶标和参考多核苷酸产生的合适的测序片段获得参考多核苷酸内的第一种。 对于每个参考数据迹线,选择对应于尺寸在40至1200个碱基范围内的片段的多个峰。 基准号被分配给参考数据轨迹中的每个选定的峰,并且创建具有关于峰值和迁移时间(或距离)的信息的数值“峰值文件”。 分析该峰值文件以确定一组多项式系数,其将允许峰值数量对相邻峰值之间的分离和迹线相对于彼此的对准的实质线性化。 这些系数用于产生校正时间标度,以确定哪些峰应位于给定的实验凝胶上。 该校正时间标度用于指导实验数据的采样,以及数据中峰的分配。