Evaluating the predictive accuracy of curated biological pathways in a public knowledgebase.
Evaluating the predictive accuracy of curated biological pathways in a public knowledgebase.
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评估公共知识库中策划的生物途径的预测准确性。
DOI：
10.1093/database/baac009
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发表时间：
2022-03-28
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Reactome是一个人类生物途径的数据库，由主要文献手工精选，并由专家同行评审。为了评估反应组途径在预测遗传扰动的功能后果方面的有效性，我们将基于反应组途径的扰动效应预测与已发表的经验观察结果进行了比较。选择了10条与癌症相关的反应组途径进行测试，这些途径代表了信号转导、细胞分裂、DNA修复和转录调控等不同的生物学过程。对于每条路径，定义了根输入节点和关键路径输出。然后，我们使用路径图衍生的逻辑图来预测，通过生物计算器的检查或使用一种新的算法MP-BioPath，单根输入的双向扰动(上调/激活或下调/抑制)对关键输出状态的影响。然后将这些预测与已发表的经验测试进行比较。总共分析了10条路径上的4968个测试案例，其中847个得到了已发表的经验研究结果的支持。在847个测试案例中，策展人的预测与实验证据一致的有670个，不一致的有177个，结果∼的总体准确率为81%。MP-BioPath的预测与625个测试案例的实验证据一致，而对222个测试案例的预测不一致，导致∼的总体准确率达到75%。随机猜测的预期准确率为33%。每条路径的准确率与路径边缘数和路径节点数无关，但在不同路径上存在差异，从56%(管理者)/44%(MP-BioPath)(有丝分裂G1期和G1/S转变)到100%(管理者)/94%(MP-BioPath)(RAF/MAP激酶级联)。这项研究强调了像Reactome这样的途径数据库在对遗传扰动进行建模、促进实验途径活动读数的标准化以及通过揭示尚未直接进行实验测试的途径输入和输出之间的关系来支持假说驱动的研究方面的潜力。Www.reactome.org
Reactome is a database of human biological pathways manually curated from the primary literature and peer-reviewed by experts. To evaluate the utility of Reactome pathways for predicting functional consequences of genetic perturbations, we compared predictions of perturbation effects based on Reactome pathways against published empirical observations. Ten cancer-relevant Reactome pathways, representing diverse biological processes such as signal transduction, cell division, DNA repair and transcriptional regulation, were selected for testing. For each pathway, root input nodes and key pathway outputs were defined. We then used pathway-diagram-derived logic graphs to predict, either by inspection by biocurators or using a novel algorithm MP-BioPath, the effects of bidirectional perturbations (upregulation/activation or downregulation/inhibition) of single root inputs on the status of key outputs. These predictions were then compared to published empirical tests. In total, 4968 test cases were analyzed across 10 pathways, of which 847 were supported by published empirical findings. Out of the 847 test cases, curators’ predictions agreed with the experimental evidence in 670 and disagreed in 177 cases, resulting in ∼81% overall accuracy. MP-BioPath predictions agreed with experimental evidence for 625 and disagreed for 222 test cases, resulting in ∼75% overall accuracy. The expected accuracy of random guessing was 33%. Per-pathway accuracy did not correlate with the number of pathway edges nor the number of pathway nodes but varied across pathways, ranging from 56% (curator)/44% (MP-BioPath) for ‘Mitotic G1 phase and G1/S transition’ to 100% (curator)/94% (MP-BioPath) for ‘RAF/MAP kinase cascade’. This study highlights the potential of pathway databases such as Reactome in modeling genetic perturbations, promoting standardization of experimental pathway activity readout and supporting hypothesis-driven research by revealing relationships between pathway inputs and outputs that have not yet been directly experimentally tested. www.reactome.org
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影响因子：
64.8
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影响因子：
48
作者：
Dey, Sucharita;Ritchie, David W.;Levy, Emmanuel D.
通讯作者：
Levy, Emmanuel D.
DOI：
10.1093/bioinformatics/btq182
发表时间：
2010-06-15
期刊：
Bioinformatics (Oxford, England)
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作者：
Vaske CJ;Benz SC;Sanborn JZ;Earl D;Szeto C;Zhu J;Haussler D;Stuart JM
通讯作者：
Stuart JM
DOI：
10.1007/978-1-4939-9004-7_5
发表时间：
2019-01-01
期刊：
TUMOR PROFILING: METHODS AND PROTOCOLS
影响因子：
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作者：
Fisch, Kathleen M.
通讯作者：
Fisch, Kathleen M.
影响因子：
64.5
作者：
Brewster RC;Weinert FM;Garcia HG;Song D;Rydenfelt M;Phillips R
通讯作者：
Phillips R