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Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experiments.


ABSTRACT: Characterizing functions of long noncoding RNAs (lncRNAs) remains a major challenge, mostly due to the lack of lncRNA-involved regulatory relationships. A wide array of genome-wide expression profiles generated by gene perturbation have been widely used to capture causal links between perturbed genes and response genes. Through annotating >600 gene perturbation profiles, over 354,000 causal relationships between perturbed genes and lncRNAs were identified. This large-scale resource of causal relations inspired us to develop a novel computational approach LnCAR for inferring lncRNAs' functions, which showed a higher accuracy than the co-expression based approach. By application of LnCAR to the cancer hallmark processes, we identified 38 lncRNAs involved in distinct carcinogenic processes. The "activating invasion & metastasis" related lncRNAs were strongly associated with metastatic progression in various cancer types and could act as a predictor of cancer metastasis. Meanwhile, the "evading immune destruction" related lncRNAs showed significant associations with immune infiltration of various immune cells and, importantly, can predict response to anti-PD-1 immunotherapy, suggesting their potential roles as biomarkers for immune therapy. Taken together, our approach provides a novel way to systematically reveal functions of lncRNAs, which will be helpful for further experimental exploration and clinical translational research of lncRNAs.

SUBMITTER: Xu J 

PROVIDER: S-EPMC6156711 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experiments.

Xu Jinyuan J   Shi Aiai A   Long Zhilin Z   Xu Liwen L   Liao Gaoming G   Deng Chunyu C   Yan Min M   Xie Aiming A   Luo Tao T   Huang Jian J   Xiao Yun Y   Li Xia X  

EBioMedicine 20180901


Characterizing functions of long noncoding RNAs (lncRNAs) remains a major challenge, mostly due to the lack of lncRNA-involved regulatory relationships. A wide array of genome-wide expression profiles generated by gene perturbation have been widely used to capture causal links between perturbed genes and response genes. Through annotating >600 gene perturbation profiles, over 354,000 causal relationships between perturbed genes and lncRNAs were identified. This large-scale resource of causal rel  ...[more]

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