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基于聚类相关性的 lncRNA-疾病关联预测方法。

Cluster correlation based method for lncRNA-disease association prediction.

机构信息

School of Computer Science and Technology, XIDIAN UNIVERSITY, Xi'an, Shaanxi, China.

出版信息

BMC Bioinformatics. 2020 May 11;21(1):180. doi: 10.1186/s12859-020-3496-8.

Abstract

BACKGROUND

In recent years, increasing evidences have indicated that long non-coding RNAs (lncRNAs) are deeply involved in a wide range of human biological pathways. The mutations and disorders of lncRNAs are closely associated with many human diseases. Therefore, it is of great importance to predict potential associations between lncRNAs and complex diseases for the diagnosis and cure of complex diseases. However, the functional mechanisms of the majority of lncRNAs are still remain unclear. As a result, it remains a great challenge to predict potential associations between lncRNAs and diseases.

RESULTS

Here, we proposed a new method to predict potential lncRNA-disease associations. First, we constructed a bipartite network based on known associations between diseases and lncRNAs/protein coding genes. Then the cluster association scores were calculated to evaluate the strength of the inner relationships between disease clusters and gene clusters. Finally, the gene-disease association scores are defined based on disease-gene cluster association scores and used to measure the strength for potential gene-disease associations.

CONCLUSIONS

Leave-One Out Cross Validation (LOOCV) and 5-fold cross validation tests were implemented to evaluate the performance of our method. As a result, our method achieved reliable performance in the LOOCV (AUCs of 0.8169 and 0.8410 based on Yang's dataset and Lnc2cancer 2.0 database, respectively), and 5-fold cross validation (AUCs of 0.7573 and 0.8198 based on Yang's dataset and Lnc2cancer 2.0 database, respectively), which were significantly higher than the other three comparative methods. Furthermore, our method is simple and efficient. Only the known gene-disease associations are exploited in a graph manner and further new gene-disease associations can be easily incorporated in our model. The results for melanoma and ovarian cancer have been verified by other researches. The case studies indicated that our method can provide informative clues for further investigation.

摘要

背景

近年来,越来越多的证据表明长非编码 RNA(lncRNA)广泛参与人类的各种生物学途径。lncRNA 的突变和紊乱与许多人类疾病密切相关。因此,预测 lncRNA 与复杂疾病之间的潜在关联对于复杂疾病的诊断和治疗具有重要意义。然而,大多数 lncRNA 的功能机制仍不清楚。因此,预测 lncRNA 与疾病之间的潜在关联仍然是一个巨大的挑战。

结果

在这里,我们提出了一种新的方法来预测潜在的 lncRNA-疾病关联。首先,我们基于疾病和 lncRNA/蛋白质编码基因之间的已知关联构建了一个二分网络。然后计算簇关联分数以评估疾病簇和基因簇之间的内部关系的强度。最后,基于疾病-基因簇关联分数定义基因-疾病关联分数,以衡量潜在基因-疾病关联的强度。

结论

进行了Leave-One Out Cross Validation(LOOCV)和 5 倍交叉验证测试以评估我们方法的性能。结果表明,我们的方法在 LOOCV(基于 Yang 数据集和 Lnc2cancer 2.0 数据库的 AUC 分别为 0.8169 和 0.8410)和 5 倍交叉验证(基于 Yang 数据集和 Lnc2cancer 2.0 数据库的 AUC 分别为 0.7573 和 0.8198)中均表现出可靠的性能,明显高于其他三种比较方法。此外,我们的方法简单有效。仅以图形方式利用已知的基因-疾病关联,并且可以很容易地将新的基因-疾病关联纳入我们的模型中。黑色素瘤和卵巢癌的案例研究已经被其他研究验证。案例研究表明,我们的方法可以为进一步的研究提供有价值的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/874a/7216352/aa3218ffaa32/12859_2020_3496_Fig1_HTML.jpg

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