Knowledge integration and decision support for accelerated discovery of antibiotic resistance genes.

Knowledge integration and decision support for accelerated discovery of antibiotic resistance genes.
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DOI:
10.1038/s41467-022-29993-z
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发表时间:
2022-04-29
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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我们提出了一个机器学习框架,通过知识图构建,不一致性解决和迭代链接预测来自动化知识发现。通过整合来自10个公开来源的知识,我们构建了一个大肠杆菌抗生素耐药性知识图,在解决了236组不一致性后,包含来自23种三联体类型的651,758个三联体。迭代地将链接预测应用于该图,并对生成的假设进行湿实验室验证,揭示了15种抗生素耐药的E。大肠杆菌基因,其中6个基因与任何微生物的抗生素耐药性无关。迭代链接预测导致性能改进和更多的发现。阳性结果的概率与实验验证的结果高度相关(R2 = 0.94)。我们还确定了肠道沙门氏菌中的5个同源物,这些同源物都被验证为对抗生素具有耐药性。这项工作展示了证据驱动的决策是如何以高信心和更快的速度自动化知识发现的一步,从而取代传统的耗时和昂贵的方法。在这里,作者介绍了KIDS,一个知识图集成和表型预测框架。当应用于抗生素数据时,它鉴定出6个新的抗生素耐药E.大肠杆菌基因,作者随后验证。
We present a machine learning framework to automate knowledge discovery through knowledge graph construction, inconsistency resolution, and iterative link prediction. By incorporating knowledge from 10 publicly available sources, we construct an Escherichia coli antibiotic resistance knowledge graph with 651,758 triples from 23 triple types after resolving 236 sets of inconsistencies. Iteratively applying link prediction to this graph and wet-lab validation of the generated hypotheses reveal 15 antibiotic resistant E. coli genes, with 6 of them never associated with antibiotic resistance for any microbe. Iterative link prediction leads to a performance improvement and more findings. The probability of positive findings highly correlates with experimentally validated findings (R2 = 0.94). We also identify 5 homologs in Salmonella enterica that are all validated to confer resistance to antibiotics. This work demonstrates how evidence-driven decisions are a step toward automating knowledge discovery with high confidence and accelerated pace, thereby substituting traditional time-consuming and expensive methods. Here the authors present KIDS, a knowledge graph integration and phenotypic prediction framework. When applied on antibiotic data, it identifies 6 novel antibiotic resistant E. coli genes that the authors subsequently validate.
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