背景:环状RNA(circularRNAs)已被证实在疾病的发生和发展中起着至关重要的作用。探索circRNAs与疾病之间的关系对于研究病因和治疗疾病具有深远的意义。为此,基于我们以前的工作GMNN2CD中构造的图马尔可夫神经网络算法(GMNN),我们进一步考虑了影响circRNA与疾病之间关联的多源生物学数据,并基于人类肝细胞癌(HCC)组织数据开发了一个更新的网络服务器CircDA,以验证CircDA的预测结果.
结果:CircDA建立在基于Tumarkov的深度学习框架之上。该算法将生物分子视为节点,将分子之间的相互作用视为边缘,合理地抽象多组学数据,并将它们建模为异质生物分子缔合网络,可以反映不同生物分子之间的复杂关系。使用HCC的文献资料进行案例研究,子宫颈,和胃癌表明CircDA预测因子可以识别已知的circRNAs和疾病之间缺失的关联,并采用实时荧光定量PCR(RT-qPCR)实验,发现五个circRNAs显著差异表达,这证明CircDA可以预测与新的circRNAs相关的疾病。
结论:这种具有足够反馈的有效计算预测和案例分析使我们能够识别circRNA相关疾病和疾病相关circRNAs。我们的工作提供了一种预测circRNA相关疾病的方法,并且可以为疾病与某些circRNA的关联提供指导。为了便于使用,在线预测服务器(http://server。malab.cn/CircDA)提供,代码是开源的(https://github.com/nmt315320/CircDA。git)以方便算法改进。
BACKGROUND: Circular RNAs (circRNAs) have been confirmed to play a vital role in the occurrence and development of diseases. Exploring the relationship between circRNAs and diseases is of far-reaching significance for studying etiopathogenesis and treating diseases. To this end, based on the graph Markov neural network algorithm (GMNN) constructed in our previous work GMNN2CD, we further considered the multisource biological data that affects the association between circRNA and disease and developed an updated web server CircDA and based on the human hepatocellular carcinoma (HCC) tissue data to verify the prediction results of CircDA.
RESULTS: CircDA is built on a Tumarkov-based deep learning framework. The algorithm regards biomolecules as nodes and the interactions between molecules as edges, reasonably abstracts multiomics data, and models them as a heterogeneous biomolecular association network, which can reflect the complex relationship between different biomolecules.
Case studies using literature data from HCC, cervical, and gastric cancers demonstrate that the CircDA predictor can identify missing associations between known circRNAs and diseases, and using the quantitative real-time PCR (RT-qPCR) experiment of HCC in human tissue samples, it was found that five circRNAs were significantly differentially expressed, which proved that CircDA can predict diseases related to new circRNAs.
CONCLUSIONS: This efficient computational prediction and
case analysis with sufficient feedback allows us to identify circRNA-associated diseases and disease-associated circRNAs. Our work provides a method to predict circRNA-associated diseases and can provide guidance for the association of diseases with certain circRNAs. For ease of use, an online prediction server ( http://server.malab.cn/CircDA ) is provided, and the code is open-sourced ( https://github.com/nmt315320/CircDA.git ) for the convenience of algorithm improvement.