Choice of transcripts and software has a large effect on variant annotation.
Choice of transcripts and software has a large effect on variant annotation.
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DOI：
10.1186/gm543
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发表时间：
2014
期刊：
影响因子：
12.3
通讯作者：
Donnelly P
中科院分区：
文献类型：
--
作者：
McCarthy DJ;Humburg P;Kanapin A;Rivas MA;Gaulton K;Cazier JB;Donnelly P
变异注释是基因组测序数据分析中的关键步骤。功能注释结果对疾病研究的最终结论有很大的影响。不正确或不完整的注释可能会导致研究人员忽视潜在的疾病相关的DNA变异，并在假阳性池中稀释有趣的变异。研究人员普遍意识到这些问题，但最终结果对用于注释的转录本和软件的选择的依赖程度尚未详细量化。本文量化了全基因组测序研究中8000万个变体注释的差异程度。我们使用RefSeq和Ensembl转录本集作为变异注释的基础，使用Annovar软件比较结果，并且还比较了使用Ensembl转录本时来自两个注释软件包Annovar和VEP（Ensembl的变异效应预测器）的结果。我们发现，当使用RefSeq和Ensembl转录本集作为Annovar注释的基础时，推定的功能丧失变体的注释只有44%的一致性。功能丧失和非同义变体的注释匹配率为79%，所有外显子变体的注释匹配率为83%。当使用Ensembl转录本比较Annovar和VEP的结果时，仅在65%的功能丧失变体和87%的所有外显子变体中观察到匹配的注释，剪接变体显示为差异最大的类别。使用这些比较，我们的特点是由Annovar和VEP的明显错误的类型，并讨论其对基因组测序研究中的DNA变异分析的影响。变体注释是一个尚未解决的问题。转录本集的选择可能对全基因组测序研究中获得的最终变体注释有很大影响。注释软件的选择也会产生实质性的影响。因此，必须仔细考虑基因组测序研究分析中的注释步骤，并有意识地选择使用哪种转录本集和软件进行注释。
Variant annotation is a crucial step in the analysis of genome sequencing data. Functional annotation results can have a strong influence on the ultimate conclusions of disease studies. Incorrect or incomplete annotations can cause researchers both to overlook potentially disease-relevant DNA variants and to dilute interesting variants in a pool of false positives. Researchers are aware of these issues in general, but the extent of the dependency of final results on the choice of transcripts and software used for annotation has not been quantified in detail. This paper quantifies the extent of differences in annotation of 80 million variants from a whole-genome sequencing study. We compare results using the RefSeq and Ensembl transcript sets as the basis for variant annotation with the software Annovar, and also compare the results from two annotation software packages, Annovar and VEP (Ensembl’s Variant Effect Predictor), when using Ensembl transcripts. We found only 44% agreement in annotations for putative loss-of-function variants when using the RefSeq and Ensembl transcript sets as the basis for annotation with Annovar. The rate of matching annotations for loss-of-function and nonsynonymous variants combined was 79% and for all exonic variants it was 83%. When comparing results from Annovar and VEP using Ensembl transcripts, matching annotations were seen for only 65% of loss-of-function variants and 87% of all exonic variants, with splicing variants revealed as the category with the greatest discrepancy. Using these comparisons, we characterised the types of apparent errors made by Annovar and VEP and discuss their impact on the analysis of DNA variants in genome sequencing studies. Variant annotation is not yet a solved problem. Choice of transcript set can have a large effect on the ultimate variant annotations obtained in a whole-genome sequencing study. Choice of annotation software can also have a substantial effect. The annotation step in the analysis of a genome sequencing study must therefore be considered carefully, and a conscious choice made as to which transcript set and software are used for annotation.
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影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
14.9
作者：
Fujita PA;Rhead B;Zweig AS;Hinrichs AS;Karolchik D;Cline MS;Goldman M;Barber GP;Clawson H;Coelho A;Diekhans M;Dreszer TR;Giardine BM;Harte RA;Hillman-Jackson J;Hsu F;Kirkup V;Kuhn RM;Learned K;Li CH;Meyer LR;Pohl A;Raney BJ;Rosenbloom KR;Smith KE;Haussler D;Kent WJ
通讯作者：
Kent WJ
影响因子：
5.8
作者：
Danecek, Petr;Auton, Adam;Durbin, Richard
通讯作者：
Durbin, Richard
DOI：
10.1038/ejhg.2011.28
发表时间：
2011-07
期刊：
European journal of human genetics : EJHG
影响因子：
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作者：
通讯作者：
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