Automated splicing mutation analysis by information theory
Automated splicing mutation analysis by information theory
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DOI：
10.1002/humu.20151
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发表时间：
2005-01-01
期刊：
影响因子：
3.9
通讯作者：
Rogan, PK
中科院分区：
文献类型：
--
作者：
Nalla, VK;Rogan, PK
基于信息理论的软件工具在解释非编码序列变异的功能序列元素（如剪接位点）方面非常有用。个体信息分析检测激活的隐剪接位点和相关的剪接调控位点，并能够区分零和部分功能等位基因。我们提供了一个服务器（https://splice.cmh.edu），用于分析人类基因、基因组、映射mrna、用户定义序列或dbSNP条目中结合位点的剪接突变。标准的hugo批准的基因符号和hgvs批准的系统突变命名法（或dbSNP格式）通过web门户输入。在验证输入变量的准确性后，从人类基因组或用户提供的参考序列中检索周围区间。然后，服务器计算参考序列和变异序列中所有潜在的构成和/或调节剪接位点的信息内容（R-i）。信息内容的变化以颜色编码、制表和可视化的方式显示为序列行走器，它显示具有参考序列的结合位点。该软件通过分析来自Human Mutation的1300个类似的突变以及来自dbSNP的8个被指定为剪接位点变异的映射snp来验证。所有的剪接突变和变异体都会影响剪接位点的强度或激活隐剪接位点。该服务器还检测到一些误义突变，这些突变出乎意料地预测对剪接有伴随影响，或者似乎激活了隐剪接。(c) 2005 Wiley Liss, Inc。
Information theory-based software tools have been useful in interpreting noncoding sequence variation within functional sequence elements such as splice sites. Individual information analysis detects activated cryptic splice sites and associated splicing regulatory sites and is capable of distinguishing null from partially functional alleles. We present a server (https://splice.cmh.edu) designed to analyze splicing mutations in binding sites in either human genes, genome,mapped mRNAs, user-defined sequences, or dbSNP entries. Standard HUGO-approved gene symbols and HGVS-approved systematic mutation nomenclature (or dbSNP format) are entered via a web portal. After verifying the accuracy of input variant(s), the surrounding interval is retrieved from the human genome or user-supplied reference sequence. The server then computes the information contents (R-i) of all potential constitutive and/or regulatory splice sites in both the reference and variant sequences. Changes in information content are color-coded, tabulated, and visualized as sequence walkers, which display the binding sites with the reference sequence. The software was validated by analyzing similar to 1,300 mutations from Human Mutation as well as eight mapped SNPs from dbSNP designated as splice site variants. All of the splicing mutations and variants affected splice site strength or activated cryptic splice sites. The server also detected several missense mutations that were unexpectedly predicted to have concomitant effects on splicing or appeared to activate cryptic splicing. (c) 2005 Wiley Liss, Inc.