Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges.
Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges.
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DOI：
10.1002/humu.23265
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发表时间：
2017-09
期刊：
影响因子：
3.9
通讯作者：
Mooney SD
中科院分区：
文献类型：
--
作者：
Cai B;Li B;Kiga N;Thusberg J;Bergquist T;Chen YC;Niknafs N;Carter H;Tokheim C;Beleva-Guthrie V;Douville C;Bhattacharya R;Yeo HTG;Fan J;Sengupta S;Kim D;Cline M;Turner T;Diekhans M;Zaucha J;Pal LR;Cao C;Yu CH;Yin Y;Carraro M;Giollo M;Ferrari C;Leonardi E;Tosatto SCE;Bobe J;Ball M;Hoskins RA;Repo S;Church G;Brenner SE;Moult J;Gough J;Stanke M;Karchin R;Mooney SD
下一代测序技术的出现大大降低了全基因组测序的成本，并增加了其在研究和临床护理中应用的可行性。个人基因组计划（PGP）提供了对个人基因组及其相关表型的不受限制的访问。该资源使基因组解释的关键评估（CAGI）能够创建一个社区挑战，以评估生物信息学社区从整个基因组预测性状的能力。在CAGI PGP挑战赛中，研究人员被要求根据整个基因组预测一个人是否具有特定的特征或特征。使用了几种方法来评估提交的数据，包括ROC AUC（受试者工作特征曲线下面积）、概率排名、正确预测的数量和统计学显著性模拟。总的来说，我们发现预测个体特征是困难的，依赖于对一般人群中特征频率的深入了解，而将基因组与特征谱相匹配在很大程度上依赖于少数常见特征，包括祖先，血型和眼睛颜色。当存在罕见遗传疾病时，当鉴定出一种或多种致病性变体时，可以匹配谱。在过去的6年里，由于方法的改进和对特征的更好理解，预测准确性大大提高。
The advent of next-generation sequencing has dramatically decreased the cost for whole-genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community’s ability to predict traits from whole genomes. In the CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome. Several approaches were used to assess submissions, including ROC AUC (area under receiver operating characteristic curve), probability rankings, the number of correct predictions, and statistical significance simulations. Overall, we found that prediction of individual traits is difficult, relying on a strong knowledge of trait frequency within the general population, whereas matching genomes to trait profiles relies heavily upon a small number of common traits including ancestry, blood type, and eye color. When a rare genetic disorder is present, profiles can be matched when one or more pathogenic variants are identified. Prediction accuracy has improved substantially over the last 6 years due to improved methodology and a better understanding of features.
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DOI：
10.1126/science.1219240
发表时间：
2012-07-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tennessen JA;Bigham AW;O'Connor TD;Fu W;Kenny EE;Gravel S;McGee S;Do R;Liu X;Jun G;Kang HM;Jordan D;Leal SM;Gabriel S;Rieder MJ;Abecasis G;Altshuler D;Nickerson DA;Boerwinkle E;Sunyaev S;Bustamante CD;Bamshad MJ;Akey JM;Broad GO;Seattle GO;NHLBI Exome Sequencing Project
通讯作者：
NHLBI Exome Sequencing Project
影响因子：
3.9
作者：
Shihab, Hashem A.;Gough, Julian;Cooper, David N.;Stenson, Peter D.;Barker, Gary L. A.;Edwards, Keith J.;Day, Ian N. M.;Gaunt, Tom R.
通讯作者：
Gaunt, Tom R.
影响因子：
14.9
作者：
Fang H;Gough J
通讯作者：
Gough J
影响因子：
4.4
作者：
Carter H;Douville C;Stenson PD;Cooper DN;Karchin R
通讯作者：
Karchin R
影响因子：
3.9
作者：
Douville, Christopher;Masica, David L.;Stenson, Peter D.;Cooper, David N.;Gygax, Derek M.;Kim, Rick;Ryan, Michael;Karchin, Rachel
通讯作者：
Karchin, Rachel