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Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs
Published on: June 12, 2018
A pseudotemporal causality approach to identifying miRNA-mRNA interactions during biological processes
Andres M Cifuentes-Bernal1, Vu Vh Pham1, Xiaomei Li1
1UniSA STEM, University of South Australia, Adelaide, South Australia, 5095 Mawson Lakes, Australia.
Motivation:
microRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA-mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process. The recent development of single cell data and the booming of the exploration of cell trajectories using 'pseudotime' concept have inspired us to develop a pseudotime-based method to infer the miRNA-mRNA relationships characterizing a biological process by taking into account the temporal aspect of the process.
Results:
We have developed a novel approach, called pseudotime causality, to find the causal relationships between miRNAs and mRNAs during a biological process. We have applied the proposed method to both single cell and bulk sequencing datasets for Epithelia to Mesenchymal Transition, a key process in cancer metastasis. The evaluation results show that our method significantly outperforms existing methods in finding miRNA-mRNA interactions in both single cell and bulk data. The results suggest that utilizing the pseudotemporal information from the data helps reveal the gene regulation in a biological process much better than using the static information.
Availability And Implementation:
R scripts and datasets can be found at https://github.com/AndresMCB/PTC.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
Insights
We developed pseudotime causality, a new method to uncover microRNA-mRNA interactions in biological processes. This approach significantly improves upon existing methods by incorporating temporal dynamics, offering better insights into gene regulation.
Area of Science:
- Genomics
- Computational Biology
- Molecular Biology
Background:
- microRNAs (miRNAs) are key gene regulators involved in biological processes, including cancer progression.
- Accurate identification of miRNA-mRNA interactions is crucial for understanding gene regulation.
- Existing computational methods often overlook the dynamic nature of biological processes, relying on static data snapshots.
Purpose of the Study:
- To develop a novel computational method for inferring miRNA-mRNA relationships that accounts for the temporal dynamics of biological processes.
- To leverage single-cell data and the concept of 'pseudotime' for a more accurate understanding of gene regulation.
Main Methods:
- Developed a pseudotime-based method named 'pseudotime causality' to infer causal miRNA-mRNA relationships.
- Applied the method to both single-cell and bulk sequencing datasets.
- Utilized Epithelial-to-Mesenchymal Transition (EMT) as a model biological process, a key event in cancer metastasis.
Main Results:
- The pseudotime causality method significantly outperforms existing approaches in identifying miRNA-mRNA interactions.
- The method demonstrated superior performance on both single-cell and bulk sequencing data.
- Incorporating pseudotemporal information enhances the revelation of gene regulatory mechanisms during biological processes.
Conclusions:
- Pseudotime causality offers a powerful new approach for understanding dynamic gene regulation.
- The method's ability to utilize temporal data provides a more comprehensive view of miRNA-mRNA interactions compared to static methods.
- This approach has significant implications for cancer research and understanding other dynamic biological processes.
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