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Computational detection of significant variation in binding affinity across two sets of sequences with application to the analysis of replication origins in yeast.

作者信息

Keich Uri, Gao Hong, Garretson Jeffrey S, Bhaskar Anand, Liachko Ivan, Donato Justin, Tye Bik K

机构信息

Department of Computer Science, Cornell University, Ithaca, NY 14853, USA.

出版信息

BMC Bioinformatics. 2008 Sep 12;9:372. doi: 10.1186/1471-2105-9-372.

DOI:10.1186/1471-2105-9-372
PMID:18786274
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2566582/
Abstract

BACKGROUND

In analyzing the stability of DNA replication origins in Saccharomyces cerevisiae we faced the question whether one set of sequences is significantly enriched in the number and/or the quality of the matches of a particular position weight matrix relative to another set.

RESULTS

We present SADMAMA, a computational solution to a address this problem. SADMAMA implements two types of statistical tests to answer this question: one type is based on simplified models, while the other relies on bootstrapping, and as such might be preferable to users who are averse to such models. The bootstrap approach incorporates a novel "site-protected" resampling procedure which solves a problem we identify with naive resampling.

CONCLUSION

SADMAMA's utility is demonstrated here by offering a plausible explanation to the differential ARS activity observed in our previous mcm1-1 mutant experiments 1, by suggesting the relevance of multiple weak ACS matches to efficient replication origin function in Saccharomyces cerevisiae, and by suggesting an explanation to the observed negative effect FKH2 has on chromatin silencing 2. SADMAMA is available for download from http://www.cs.cornell.edu/~keich/.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/592c38225716/1471-2105-9-372-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/5ad4e71ddae4/1471-2105-9-372-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/5fba2af2bf96/1471-2105-9-372-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/592c38225716/1471-2105-9-372-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/5ad4e71ddae4/1471-2105-9-372-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/5fba2af2bf96/1471-2105-9-372-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b58a/2566582/592c38225716/1471-2105-9-372-3.jpg

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本文引用的文献

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Using TESS to predict transcription factor binding sites in DNA sequence.使用TESS预测DNA序列中的转录因子结合位点。
Curr Protoc Bioinformatics. 2008 Mar;Chapter 2:Unit 2.6. doi: 10.1002/0471250953.bi0206s21.
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Cell cycle regulation of DNA replication.DNA复制的细胞周期调控
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Connecting protein structure with predictions of regulatory sites.将蛋白质结构与调控位点预测相联系。
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Statistical tests to compare motif count exceptionalities.用于比较基序计数异常情况的统计检验。
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Computing exact P-values for DNA motifs.计算DNA基序的精确P值。
Bioinformatics. 2007 Mar 1;23(5):531-7. doi: 10.1093/bioinformatics/btl662. Epub 2007 Jan 18.
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OriDB: a DNA replication origin database.OriDB:一个DNA复制起点数据库。
Nucleic Acids Res. 2007 Jan;35(Database issue):D40-6. doi: 10.1093/nar/gkl758. Epub 2006 Oct 25.
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The spatial arrangement of ORC binding modules determines the functionality of replication origins in budding yeast.ORC结合模块的空间排列决定了芽殖酵母中复制起点的功能。
Nucleic Acids Res. 2006;34(18):5069-80. doi: 10.1093/nar/gkl661. Epub 2006 Sep 19.
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Genome-wide hierarchy of replication origin usage in Saccharomyces cerevisiae.酿酒酵母中复制起点使用的全基因组层次结构。
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