UMD-Predictor: A High-Throughput Sequencing Compliant System for Pathogenicity Prediction of any Human cDNA Substitution.
UMD-Predictor: A High-Throughput Sequencing Compliant System for Pathogenicity Prediction of any Human cDNA Substitution.
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DOI：
10.1002/humu.22965
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发表时间：
2016-05
期刊：
影响因子：
3.9
通讯作者：
Beroud, Christophe
中科院分区：
文献类型：
--
作者：
Salgado, David;Desvignes, Jean-Pierre;Rai, Ghadi;Blanchard, Arnaud;Miltgen, Morgane;Pinard, Amelie;Levy, Nicolas;Collod-Beroud, Gwenaelle;Beroud, Christophe
全外显子组测序技术越来越多地应用于人类疾病的研究和临床诊断。它通常会导致大量的基因变异。根据遗传模式的不同，只有一到两个对应于导致这种疾病的致病突变，并存在于受影响的个人中。因此，筛选出非致病变异，并将下游分析限制在少数候选突变上是至关重要的。我们开发了一个新的计算组合系统UMD-Predictor(http://umd-Predictor.eu)来有效地注释所有人类转录本的cdna替换，以确定它们的潜在致病性。它结合了生化特性、对剪接信号的影响、在蛋白质结构域中的定位、全球种群中的变异频率以及通过BLOSUM62全球替代矩阵的保守性和100个物种中的蛋白质特异性保守性。我们使用了最大的参考变异数据集，包括超过14万个带注释的变异，将其准确性与七种最常用和可靠的预测工具进行了比较。该系统一贯表现出更好的准确性、特异度、马修斯相关系数、诊断优势比、速度，并提供了WES候选突变的最短列表。WebServices允许它在任何生物信息学管道中实施，以进行下一代测序分析。它可以为从基因发现到临床诊断的广泛用户和应用程序带来好处。
Whole‐exome sequencing (WES) is increasingly applied to research and clinical diagnosis of human diseases. It typically results in large amounts of genetic variations. Depending on the mode of inheritance, only one or two correspond to pathogenic mutations responsible for the disease and present in affected individuals. Therefore, it is crucial to filter out nonpathogenic variants and limit downstream analysis to a handful of candidate mutations. We have developed a new computational combinatorial system UMD‐Predictor (http://umd‐predictor.eu) to efficiently annotate cDNA substitutions of all human transcripts for their potential pathogenicity. It combines biochemical properties, impact on splicing signals, localization in protein domains, variation frequency in the global population, and conservation through the BLOSUM62 global substitution matrix and a protein‐specific conservation among 100 species. We compared its accuracy with the seven most used and reliable prediction tools, using the largest reference variation datasets including more than 140,000 annotated variations. This system consistently demonstrated a better accuracy, specificity, Matthews correlation coefficient, diagnostic odds ratio, speed, and provided the shortest list of candidate mutations for WES. Webservices allow its implementation in any bioinformatics pipeline for next‐generation sequencing analysis. It could benefit to a wide range of users and applications varying from gene discovery to clinical diagnosis.
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影响因子：
4.3
作者：
Bendl J;Stourac J;Salanda O;Pavelka A;Wieben ED;Zendulka J;Brezovsky J;Damborsky J
通讯作者：
Damborsky J
影响因子：
3.1
作者：
Schatz MC;Langmead B
通讯作者：
Langmead B
影响因子：
9.5
作者：
Pabinger S;Dander A;Fischer M;Snajder R;Sperk M;Efremova M;Krabichler B;Speicher MR;Zschocke J;Trajanoski Z
通讯作者：
Trajanoski Z
影响因子：
14.9
作者：
Bromberg Y;Rost B
通讯作者：
Rost B
影响因子：
14.9
作者：
Rosenbloom KR;Armstrong J;Barber GP;Casper J;Clawson H;Diekhans M;Dreszer TR;Fujita PA;Guruvadoo L;Haeussler M;Harte RA;Heitner S;Hickey G;Hinrichs AS;Hubley R;Karolchik D;Learned K;Lee BT;Li CH;Miga KH;Nguyen N;Paten B;Raney BJ;Smit AF;Speir ML;Zweig AS;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ