Systematic reanalysis of genomic data improves quality of variant interpretation.
Systematic reanalysis of genomic data improves quality of variant interpretation.
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基因组数据的系统重新分析可提高变异解释的质量。
DOI：
10.1111/cge.13259
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发表时间：
2018-07
影响因子：
3.5
通讯作者：
Cooper GM
中科院分区：
文献类型：
--
作者：
Hiatt SM;Amaral MD;Bowling KM;Finnila CR;Thompson ML;Gray DE;Lawlor JMJ;Cochran JN;Bebin EM;Brothers KB;East KM;Kelley WV;Lamb NE;Levy SE;Lose EJ;Neu MB;Rich CA;Simmons S;Myers RM;Barsh GS;Cooper GM
随着基因组测序的扩展，我们对遗传变异与疾病之间联系的了解也在不断扩展。更深入的变异频率目录可以提高良性变异的识别，而对受影响的个体进行测序可以揭示与疾病相关的变异。因此，人类遗传数据的积累使重新分析成为最大化临床测序效益的一种手段。我们实施了流程来系统地重新评估 494 名发育障碍患者的测序数据。重新分析产生了最初未在 23 名个体（此处描述的 6 名）中报道的致病性或可能致病性 (P/LP) 变异，其中 P/LP 产量增加了 16%。由于更新的群体频率数据，我们还降低了 3 个 LP 和 6 个不确定意义变体 (VUS) 的评级。随着时间的推移，识别出新的 P/LP 变体的可能性逐渐增加，约 22% 的人在最初的分析中没有收到 P/LP 变体，但三年后就发现了。我们在此表明，重新分析和数据共享可以提高临床测序的诊断率和准确性。
As genomic sequencing expands, so does our knowledge of the link between genetic variation and disease. Deeper catalogs of variant frequencies improve identification of benign variants, while sequencing affected individuals reveals disease-associated variation. Accumulation of human genetic data thus makes reanalysis a means to maximize benefits of clinical sequencing. We implemented pipelines to systematically reassess sequencing data from 494 individuals with developmental disability. Reanalysis yielded pathogenic or likely pathogenic (P/LP) variants that were not initially reported in 23 individuals, 6 described here, comprising a 16% increase in P/LP yield. We also downgraded three LP and six variants of uncertain significance (VUS) due to updated population frequency data. The likelihood of identifying a new P/LP variant increased over time, as ~22% of individuals who did not receive a P/LP variant at their original analysis subsequently did after three years. We show here that reanalysis and data sharing increase the diagnostic yield and accuracy of clinical sequencing.
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影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
14.9
作者：
Tryka KA;Hao L;Sturcke A;Jin Y;Wang ZY;Ziyabari L;Lee M;Popova N;Sharopova N;Kimura M;Feolo M
通讯作者：
Feolo M
影响因子：
12.3
作者：
Eldomery MK;Coban-Akdemir Z;Harel T;Rosenfeld JA;Gambin T;Stray-Pedersen A;Küry S;Mercier S;Lessel D;Denecke J;Wiszniewski W;Penney S;Liu P;Bi W;Lalani SR;Schaaf CP;Wangler MF;Bacino CA;Lewis RA;Potocki L;Graham BH;Belmont JW;Scaglia F;Orange JS;Jhangiani SN;Chiang T;Doddapaneni H;Hu J;Muzny DM;Xia F;Beaudet AL;Boerwinkle E;Eng CM;Plon SE;Sutton VR;Gibbs RA;Posey JE;Yang Y;Lupski JR
通讯作者：
Lupski JR
影响因子：
7
作者：
King DA;Fitzgerald TW;Miller R;Canham N;Clayton-Smith J;Johnson D;Mansour S;Stewart F;Vasudevan P;Hurles ME;DDD Study
通讯作者：
DDD Study
影响因子：
12.3
作者：
Bowling KM;Thompson ML;Amaral MD;Finnila CR;Hiatt SM;Engel KL;Cochran JN;Brothers KB;East KM;Gray DE;Kelley WV;Lamb NE;Lose EJ;Rich CA;Simmons S;Whittle JS;Weaver BT;Nesmith AS;Myers RM;Barsh GS;Bebin EM;Cooper GM
通讯作者：
Cooper GM