Functional characterization of disease/comorbidity-associated lncRNA

Abstract

Background: Functional characterization of the long noncoding RNAs (lncRNAs) in disease attracts great attention, which results in a limited number of experimentally characterized lncRNAs. The major problems underlying the lack of experimental verifications are considered to come from the significant false-positive assignments and extensive genetic-heterogeneity of disease. These problems are even worse when it comes to the functional characterization in comorbidity (simultaneous/sequential presence of multiple diseases in a patient, and showing much wider prevalence, poorer treatment-response and longer illness-course than a single disease).

Methods: Herein, FCCLnc was developed to characterize lncRNA function by (1) integrating diverse SNPs that were associated with 193 diseases standardized by International Classification of Diseases (ICD-11), (2) condition-specific expression of lncRNAs, (3) weighted correlation network of lncRNAs and protein-coding neighboring genes.

Results: FCCLnc can characterize lncRNA function in both disease and comorbidity by not only controlling false discovery but also tolerating their disease heterogeneity. Moreover, FCCLnc can provide interactive visualization and full download of lncRNA-centered co-expression network.

Conclusion: In summary, FCCLnc is unique in characterizing lncRNA function in diverse diseases and comorbidities and is highly expected to emerge to be an indispensable complement to other available tools. FCCLnc is accessible at https://idrblab.org/fcclnc/.

Author summary

Functional characterization of the long noncoding RNAs (lncRNAs) in disease attracts great attention, but has significant false-positive assignments and extensive genetic-heterogeneity of disease especially in comorbidity. Herein, FCCLnc was developed to characterize lncRNA function in diverse diseases and comorbidities, which can be expected to be an indispensable complement to other available tools.

Graphical abstract

Keywords

comorbidity / long noncoding RNA / functional characterization / disease-associated SNPs / guilt-by-association

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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at https://doi.org/10.15302/J-QB-021-0247.

AUTHOR CONTRIBUTIONS

F.Z. conceived the idea, supervised the work and wrote the manuscript. J.T., Y.W. and J.F. performed the research. J.T., Y.W. and J.F. constructed the web-server and wrote the scripts. J.T., Y.W., J.F., X.W., Z.H., C.W., M.G., Y.W., Y.D. and B.Y. prepared and analyzed the data. All authors reviewed and approved the final version of the manuscript.

ACKNOWLEDGEMENTS

This work was funded by the National Natural Science Foundation of China (81872798 & U1909208), Natural Science Foundation of Zhejiang Province (LR21H300001), National Key R&D Program of China (2018YFC0910500), Leading Talent of the “Ten Thousand Plan” ‒ National High-Level Talents Special Support Plan of China; Fundamental Research Fund for Central Universities (2018QNA7023), “Double Top-Class” University Project (181201*194232101), and Key R&D Program of Zhejiang Province (2020C03010). This work was supported by Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare; Alibaba Cloud; Information Technology Center of Zhejiang University.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Jing Tang, Yongheng Wang, Jianbo Fu, Xianglu Wu, Zhijie Han, Chuan Wang, Maiyuan Guo, Yingxiong Wang, Yubin Ding, Bo Yang and Feng Zhu declare that they have no conflict of interests or financial conflicts to disclose.

All procedures performed in studies were in accordance with the ethical standards of the institution or practice at which the studies were conducted, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

OPEN ACCESS

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