Pay attention to the application of genetic mutation site pathogenicity prediction software in ophthalmology

doi:10.3877/cma.j.issn.2095-2007.2018.06.001

Abstract

Abstract:

With the rapid development of high-throughput sequencing technology, a large number of gene mutation sites related to disease pathogenesis have been found. Pathogenicity prediction of mutation sites can provide an important reference for follow-up functional analysis. Since 2003, a variety of software for predicting the pathogenicity of gene mutation sites has been developed and continuously improved to improve the predictive effect and accuracy. In this paper, the development and characteristics of gene sequencing technology are briefly described. Thirteen pieces of single algorithm pathogenicity prediction software and six pieces of integrated prediction software with integrated algorithm are listed. Four commonly used single algorithm prediction software (SIFT, PolyPhen-2, PROVEAN and Mutation Taster) and a prediction software with integrated algorithm (CADD) were introduced. Their operation principle and application in ophthalmology are explained in order to provide theoretical and practical reference for ophthalmologists to select and use the software for predicting the pathogenicity of gene mutation sites reasonably and effectively.

Key words: Gene mutation, Pathogenicity prediction, Bioinformatics, Ophthalmology

Zhenyu Wang, Chen Huang, Xuemin Li. Pay attention to the application of genetic mutation site pathogenicity prediction software in ophthalmology[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2018, 08(06): 241-248.

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References 40

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软件名称	创建年份	输入序列类型	输出结果种类	参考数据库	优势	劣势
SIFT	2009	NCBI蛋白质ID及单个氨基酸的替换、插入及缺失突变信息	突变预测得分及致病性判断	SWISS－PROT TREMBL	设计独立致病性预测算法、包含权威数据库分析	可分析突变范围较窄，不包含剪切突变、内含子替换以及跨越内含子－外显子交界的突变
PolyPhen－2	2010	蛋白质名称或氨基酸FASTA格式、单个氨基酸替换信息	突变预测得分及致病性判断；3D结构图；基于机械学习方法的预测分类	UniRef100 SWISS－PROT	设计独立致病性预测算法、权威数据库分析及蛋白质结构功能分析，使用3D结构图直观展示蛋白质结构变异	仅能分析单个氨基酸的替换突变
PROVEAN	2012	NCBI蛋白质ID及单个氨基酸的替换、插入和缺失突变信息	突变预测得分及致病性判断	HGMD 1000 Genomes Project Uniprot UniProtKB Swiss－Prot	设计独立致病性算法、包含权威数据库分析	可分析突变范围较窄，不包含剪切突变、内含子替换以及跨越内含子－外显子交界的突变
Mutation Taster	2014	基因名称(通过GeneSidtiller联想)、单个或多个碱基替换、插入及缺失，内含子替换以及跨越内含子－外显子交界的突变信息	突变预测得分及致病性判断；phastCons和phyloP分数及不同种属	保守性数据来源： ENCODE project JASPAR 致病性数据来源： 100 Genomes Project ClinVar3 HGMD Public HapMap NNSplice	可分析突变种类广，覆盖的基因序列分析范围包括：单个或多个碱基替换、插入及缺失，内含子替换以及跨越内含子－外显子交界的突变类型；设计保守性预测算法	只检索现有权威数据库的判断，寻找已存在的突变信息

软件名称	创建年份	输入序列类型	输出结果种类	参考数据库	优势	劣势
SIFT	2009	NCBI蛋白质ID及单个氨基酸的替换、插入及缺失突变信息	突变预测得分及致病性判断	SWISS－PROT TREMBL	设计独立致病性预测算法、包含权威数据库分析	可分析突变范围较窄，不包含剪切突变、内含子替换以及跨越内含子－外显子交界的突变
PolyPhen－2	2010	蛋白质名称或氨基酸FASTA格式、单个氨基酸替换信息	突变预测得分及致病性判断；3D结构图；基于机械学习方法的预测分类	UniRef100 SWISS－PROT	设计独立致病性预测算法、权威数据库分析及蛋白质结构功能分析，使用3D结构图直观展示蛋白质结构变异	仅能分析单个氨基酸的替换突变
PROVEAN	2012	NCBI蛋白质ID及单个氨基酸的替换、插入和缺失突变信息	突变预测得分及致病性判断	HGMD 1000 Genomes Project Uniprot UniProtKB Swiss－Prot	设计独立致病性算法、包含权威数据库分析	可分析突变范围较窄，不包含剪切突变、内含子替换以及跨越内含子－外显子交界的突变
Mutation Taster	2014	基因名称(通过GeneSidtiller联想)、单个或多个碱基替换、插入及缺失，内含子替换以及跨越内含子－外显子交界的突变信息	突变预测得分及致病性判断；phastCons和phyloP分数及不同种属	保守性数据来源： ENCODE project JASPAR 致病性数据来源： 100 Genomes Project ClinVar3 HGMD Public HapMap NNSplice	可分析突变种类广，覆盖的基因序列分析范围包括：单个或多个碱基替换、插入及缺失，内含子替换以及跨越内含子－外显子交界的突变类型；设计保守性预测算法	只检索现有权威数据库的判断，寻找已存在的突变信息

软件名称	创建年份	整合软件及算法名称
Condel	2011	Logre算法，MAPP，Mutation Assessor，Polyphen－2，SIFT
CAROL	2012	PolyPhen－2，SIFT
CoVEC	2013	SIFT，Polyphen－2，SNPs&GO, Mutation Assessor
CADD	2014	四种运算模型：保守性模型(GERP，Mutation Taster，phastCons和phyloP算法))、调节信息模型、转录信息模型以及蛋白水平分数模型(Grantham评分，SIFT，PolyPhen－2)
IMHOTEP	2017	PhyloP；Grantham评分；PolyPhen－2；SNPs&GO；MutPred；SIFT；Mutation Taster；Mutation Assessor；FATHMM

软件名称	创建年份	整合软件及算法名称
Condel	2011	Logre算法，MAPP，Mutation Assessor，Polyphen－2，SIFT
CAROL	2012	PolyPhen－2，SIFT
CoVEC	2013	SIFT，Polyphen－2，SNPs&GO, Mutation Assessor
CADD	2014	四种运算模型：保守性模型(GERP，Mutation Taster，phastCons和phyloP算法))、调节信息模型、转录信息模型以及蛋白水平分数模型(Grantham评分，SIFT，PolyPhen－2)
IMHOTEP	2017	PhyloP；Grantham评分；PolyPhen－2；SNPs&GO；MutPred；SIFT；Mutation Taster；Mutation Assessor；FATHMM

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