Top-Down Crawl: a method for the ultra-rapid and motif-free alignment of sequences with associated binding metrics.

Top-Down Crawl: a method for the ultra-rapid and motif-free alignment of sequences with associated binding metrics.
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DOI:
10.1093/bioinformatics/btac653
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发表时间:
2022-11-15
期刊:
Bioinformatics (Oxford, England)
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目前可用的几种高通量蛋白质-DNA结合方法在k-mer水平上产生高度可重复的结合亲和力测量。然而,理解k聚体沿结合位点序列沿着定位的位置取决于比对。在这里,我们提出了自上而下的爬行(TDC),一个超快速的工具,设计的k-mer水平数据的排列依赖和位置权重矩阵(PWM)独立的方式对齐。由于框架仅取决于输入的等级,因此该方法可以接受来自许多类型的实验(蛋白质结合微阵列、SELEX-seq、SMiLE-seq等)的输入。而不需要专门的参数化。使用具有5重交叉验证的多元线性回归来测量对齐的性能,我们发现TDC的性能与计算昂贵的基于PWM的方法一样好或更好。TDC可以在https://topdowncrawl.usc.edu上在线运行,也可以通过pip在https://pypi.org/project/TopDownCrawl上以python包的形式在本地运行。 补充数据可在Bioinformatics在线获得。
Several high-throughput protein–DNA binding methods currently available produce highly reproducible measurements of binding affinity at the level of the k-mer. However, understanding where a k-mer is positioned along a binding site sequence depends on alignment. Here, we present Top-Down Crawl (TDC), an ultra-rapid tool designed for the alignment of k-mer level data in a rank-dependent and position weight matrix (PWM)-independent manner. As the framework only depends on the rank of the input, the method can accept input from many types of experiments (protein binding microarray, SELEX-seq, SMiLE-seq, etc.) without the need for specialized parameterization. Measuring the performance of the alignment using multiple linear regression with 5-fold cross-validation, we find TDC to perform as well as or better than computationally expensive PWM-based methods. TDC can be run online at https://topdowncrawl.usc.edu or locally as a python package available through pip at https://pypi.org/project/TopDownCrawl. Supplementary data are available at Bioinformatics online.
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