Prediction of gene-phenotype associations in humans, mice, and plants using phenologs.
Prediction of gene-phenotype associations in humans, mice, and plants using phenologs.
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DOI：
10.1186/1471-2105-14-203
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发表时间：
2013-06-21
影响因子：
3
通讯作者：
Marcotte EM
中科院分区：
文献类型：
--
作者：
Woods JO;Singh-Blom UM;Laurent JM;McGary KL;Marcotte EM
表型和疾病可能通过潜在基因的同源性与其他物种中看似不同的表型相关。这种“直向同源表型”或“表型”是深度同源性的实例，并且可以用于预测另外的候选疾病基因。在这项工作中，我们开发了一种无监督算法，通过整合k最近邻表型的预测，比较分类器和交叉验证的加权函数，对基于表型的候选疾病基因进行排名。我们还改进了原来的方法，将理论扩展到旁系同源表型。我们的算法利用了额外的表型数据-从鸡，斑马鱼，和E。大肠杆菌，以及新的数据集C. elegans -建立几种类型的注释可以被视为表型。我们展示了我们的算法的使用，以预测人类心房颤动（如HRH 2，ATP 4A，ATP 4 B和HOPX）和癫痫（例如，PAX 6和NKX 2 -1）。我们建议的候选基因药理学诱导的癫痫发作小鼠，完全基于从E。杆菌我们还探讨了植物基因-表型关联的预测，如拟南芥对春化表型的反应。我们能够对在线人类孟德尔遗传数据库中相当一部分疾病的基因预测进行排名。此外，我们的方法仅基于细菌表型和基因同源性提出哺乳动物癫痫发作的候选基因。我们表明，表型信息可能来自不同的来源，包括药物敏感性，基因本体生物过程，和原位杂交注释。最后，我们为各种人类疾病、植物性状和其他种类的表型提供了可测试的候选物。
Phenotypes and diseases may be related to seemingly dissimilar phenotypes in other species by means of the orthology of underlying genes. Such “orthologous phenotypes,” or “phenologs,” are examples of deep homology, and may be used to predict additional candidate disease genes. In this work, we develop an unsupervised algorithm for ranking phenolog-based candidate disease genes through the integration of predictions from the k nearest neighbor phenologs, comparing classifiers and weighting functions by cross-validation. We also improve upon the original method by extending the theory to paralogous phenotypes. Our algorithm makes use of additional phenotype data — from chicken, zebrafish, and E. coli, as well as new datasets for C. elegans — establishing that several types of annotations may be treated as phenotypes. We demonstrate the use of our algorithm to predict novel candidate genes for human atrial fibrillation (such as HRH2, ATP4A, ATP4B, and HOPX) and epilepsy (e.g., PAX6 and NKX2-1). We suggest gene candidates for pharmacologically-induced seizures in mouse, solely based on orthologous phenotypes from E. coli. We also explore the prediction of plant gene–phenotype associations, as for the Arabidopsis response to vernalization phenotype. We are able to rank gene predictions for a significant portion of the diseases in the Online Mendelian Inheritance in Man database. Additionally, our method suggests candidate genes for mammalian seizures based only on bacterial phenotypes and gene orthology. We demonstrate that phenotype information may come from diverse sources, including drug sensitivities, gene ontology biological processes, and in situ hybridization annotations. Finally, we offer testable candidates for a variety of human diseases, plant traits, and other classes of phenotypes across a wide array of species.
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影响因子：
4.6
作者：
Chanvivattana, Y;Bishopp, A;Goodrich, J
通讯作者：
Goodrich, J
影响因子：
2.5
作者：
DELORME, B;DAHL, E;THEVENIAU-RUISSY, M
通讯作者：
THEVENIAU-RUISSY, M
影响因子：
2.5
作者：
Bell, GW;Yatskievych, TA;Antin, PB
通讯作者：
Antin, PB
DOI：
10.1111/j.1600-0773.1992.tb00575.x
发表时间：
1992-12-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
BAGETTA, G;CORASANITI, MT;STEPHENSON, JD
通讯作者：
STEPHENSON, JD
影响因子：
5.7
作者：
He, Gonghao;Hu, Jing;Luo, Xiaoxing
通讯作者：
Luo, Xiaoxing