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Multiplexed Isothermal Amplification Based Diagnostic Platform to Detect Zika, Chikungunya, and Dengue 1
Published on: March 13, 2018
Two-stage ML Classifier for Identifying Host Protein Targets of the Dengue Protease
Jacob T Stanley1, Alison R Gilchrist, Alex C Stabell
1Molecular, Cellular and Developmental Biology, BioFrontiers Institute, University of Colorado, Boulder, CO 80305, USA.
Abstract:
Flaviviruses such as dengue encode a protease that is essential for viral replication. The protease functions by cleaving well-conserved positions in the viral polyprotein. In addition to the viral polyprotein, the dengue protease cleaves at least one host protein involved in immune response. This raises the question, what other host proteins are targeted and cleaved? Here we present a new computational method for identifying putative host protein targets of the dengue virus protease. Our method relies on biochemical and secondary structure features at the known cleavage sites in the viral polyprotein in a two-stage classification process to identify putative cleavage targets. The accuracy of our predictions scaled inversely with evolutionary distance when we applied it to the known cleavage sites of several other flaviviruses-a good indication of the validity of our predictions. Ultimately, our classifier identified 257 human protein sites possessing both a similar target motif and accessible local structure. These proteins are promising candidates for further investigation. As the number of viral sequences expands, our method could be adopted to predict host targets of other flaviviruses.
Insights
Dengue virus protease cleaves viral and host proteins. A new computational method identifies 257 potential human protein targets for dengue protease, aiding future research into viral-host interactions.
Area of Science:
- Virology
- Computational Biology
- Biochemistry
Background:
- Flaviviruses, including dengue, utilize a protease crucial for viral replication.
- This protease cleaves viral polyproteins and at least one host immune protein.
- The full range of host proteins targeted by dengue protease remains largely unknown.
Purpose of the Study:
- To develop a computational method for identifying potential host protein targets of the dengue virus protease.
- To investigate host proteins susceptible to cleavage by the dengue protease.
Main Methods:
- A two-stage classification process was employed, utilizing biochemical and secondary structure features from known viral cleavage sites.
- The method was validated by assessing prediction accuracy against evolutionary distance across different flaviviruses.
- A computational classifier was developed to identify human protein sites with suitable target motifs and local structures.
Main Results:
- The prediction accuracy demonstrated an inverse correlation with evolutionary distance, supporting the method's validity.
- The computational classifier identified 257 potential human protein cleavage sites.
- These identified sites possess characteristics similar to known viral cleavage sites and accessible local structures.
Conclusions:
- The developed computational method effectively predicts host protein targets for dengue virus protease.
- The 257 identified human proteins represent promising candidates for further experimental investigation.
- This approach can be extended to predict host targets for other flaviviruses as more sequence data becomes available.
