Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection.
Flexible Mixture Model Approaches That Accommodate Footprint Size Variability for Robust Detection of Balancing Selection.
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DOI：
10.1093/molbev/msaa134
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发表时间：
2020-11-01
影响因子：
10.7
通讯作者：
DeGiorgio M
中科院分区：
文献类型：
--
作者：
Cheng X;DeGiorgio M
长期平衡选择通常留下增加的遗传多样性的狭窄足迹，并且因此大多数检测方法仅在足够小的基因组区域（即，窗口）进行检查。这样的方法对窗口大小敏感，并且当窗口较大时遭受功率的显著损失。在这里，我们采用混合模型来构造一组五个复合似然比检验统计量，我们统称为B统计量。这些统计信息与窗口大小无关，可以对不同形式的输入数据进行操作。通过模拟，我们表明，他们表现出相当的权力，目前表现最好的方法，并保持相当高的功率，无论窗口大小。它们还显示出对高突变率和不均匀重组景观以及一系列其他常见混淆情况的相当强的鲁棒性。此外，我们将特定版本的B统计量（称为B2）应用于人类群体基因组数据集，并从先前的研究中恢复了许多顶级候选者，包括当时未表征的STPG 2和CCDC 169-SOHLH 2，两者都与配子功能有关。我们进一步将B2应用于倭黑猩猩种群基因组数据集。除了MHC-DQ基因，我们还发现了几个新的候选基因，如参与病毒防御的KLRD 1和与疼痛感知相关的SCN 9A。最后，我们表明，我们的方法可以扩展到多等位基因平衡选择，并将一组统计数据集成到名为BalLeRMix的开源软件中，供科学界将来应用。
Long-term balancing selection typically leaves narrow footprints of increased genetic diversity, and therefore most detection approaches only achieve optimal performances when sufficiently small genomic regions (i.e., windows) are examined. Such methods are sensitive to window sizes and suffer substantial losses in power when windows are large. Here, we employ mixture models to construct a set of five composite likelihood ratio test statistics, which we collectively term B statistics. These statistics are agnostic to window sizes and can operate on diverse forms of input data. Through simulations, we show that they exhibit comparable power to the best-performing current methods, and retain substantially high power regardless of window sizes. They also display considerable robustness to high mutation rates and uneven recombination landscapes, as well as an array of other common confounding scenarios. Moreover, we applied a specific version of the B statistics, termed B2, to a human population-genomic data set and recovered many top candidates from prior studies, including the then-uncharacterized STPG2 and CCDC169–SOHLH2, both of which are related to gamete functions. We further applied B2 on a bonobo population-genomic data set. In addition to the MHC-DQ genes, we uncovered several novel candidate genes, such as KLRD1, involved in viral defense, and SCN9A, associated with pain perception. Finally, we show that our methods can be extended to account for multiallelic balancing selection and integrated the set of statistics into open-source software named BalLeRMix for future applications by the scientific community.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
3.2
作者：
de Groot, Natasja G.;Heijmans, Corrine M. C.;Bontrop, Ronald E.
通讯作者：
Bontrop, Ronald E.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.3
作者：
Bitarello BD;de Filippo C;Teixeira JC;Schmidt JM;Kleinert P;Meyer D;Andrés AM
通讯作者：
Andrés AM
DOI：
10.1126/science.aag2602
发表时间：
2016-10-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Manuel M;Kuhlwilm M;Frandsen P;Sousa VC;Desai T;Prado-Martinez J;Hernandez-Rodriguez J;Dupanloup I;Lao O;Hallast P;Schmidt JM;Heredia-Genestar JM;Benazzo A;Barbujani G;Peter BM;Kuderna LF;Casals F;Angedakin S;Arandjelovic M;Boesch C;Kühl H;Vigilant L;Langergraber K;Novembre J;Gut M;Gut I;Navarro A;Carlsen F;Andrés AM;Siegismund HR;Scally A;Excoffier L;Tyler-Smith C;Castellano S;Xue Y;Hvilsom C;Marques-Bonet T
通讯作者：
Marques-Bonet T