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A computational method for predicting nucleocapsid protein in retroviruses.

ABSTRACT: Nucleocapsid protein (NC) in the group-specific antigen (gag) of retrovirus is essential in the interactions of most retroviral gag proteins with RNAs. Computational method to predict NCs would benefit subsequent structure analysis and functional study on them. However, no computational method to predict the exact locations of NCs in retroviruses has been proposed yet. The wide range of length variation of NCs also increases the difficulties. In this paper, a computational method to identify NCs in retroviruses is proposed. All available retrovirus sequences with NC annotations were collected from NCBI. Models based on random forest (RF) and weighted support vector machine (WSVM) were built to predict initiation and termination sites of NCs. Factor analysis scales of generalized amino acid information along with position weight matrix were utilized to generate the feature space. Homology based gene prediction methods were also compared and integrated to bring out better predicting performance. Candidate initiation and termination sites predicted were then combined and screened according to their intervals, decision values and alignment scores. All available gag sequences without NC annotations were scanned with the model to detect putative NCs. Geometric means of sensitivity and specificity generated from prediction of initiation and termination sites under fivefold cross-validation are 0.9900 and 0.9548 respectively. 90.91% of all the collected retrovirus sequences with NC annotations could be predicted totally correct by the model combining WSVM, RF and simple alignment. The composite model performs better than the simplex ones. 235 putative NCs in unannotated gags were detected by the model. Our prediction method performs well on NC recognition and could also be expanded to solve other gene prediction problems, especially those whose training samples have large length variations.

SUBMITTER: Guo M

PROVIDER: S-EPMC8752852 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHuman T-cell leukemia viruses (HTLV) tend to induce some fatal human diseases like Adult T-cell Leukemia (ATL) by targeting human T lymphocytes. To indentify the protein-protein interactions (PPI) between HTLV viruses and Homo sapiens is one of the significant approaches to reveal the underlying mechanism of HTLV infection and host defence. At present, as biological experiments are labor-intensive and expensive, the identified part of the HTLV-human PPI networks is rather small. Although recent years have witnessed much progress in computational modeling for reconstructing pathogen-host PPI networks, data scarcity and data unavailability are two major challenges to be effectively addressed. To our knowledge, no computational method for proteome-wide HTLV-human PPI networks reconstruction has been reported.ResultsIn this work we develop Multi-instance Adaboost method to conduct homolog knowledge transfer for computationally reconstructing proteome-wide HTLV-human PPI networks. In this method, the homolog knowledge in the form of gene ontology (GO) is treated as auxiliary homolog instance to address the problems of data scarcity and data unavailability, while the potential negative knowledge transfer is automatically attenuated by AdaBoost instance reweighting. The cross validation experiments show that the homolog knowledge transfer in the form of independent homolog instances can effectively enrich the feature information and substitute for the missing GO information. Moreover, the independent tests show that the method can validate 70.3% of the recently curated interactions, significantly exceeding the 2.1% recognition rate by the HT-Y2H experiment. We have used the method to reconstruct the proteome-wide HTLV-human PPI networks and further conducted gene ontology based clustering of the predicted networks for further biomedical research. The gene ontology based clustering analysis of the predictions provides much biological insight into the pathogenesis of HTLV retroviruses.ConclusionsThe Multi-instance AdaBoost method can effectively address the problems of data scarcity and data unavailability for the proteome-wide HTLV-human PPI interaction networks reconstruction. The gene ontology based clustering analysis of the predictions reveals some important signaling pathways and biological modules that HTLV retroviruses are likely to target.

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A computational method for predicting nucleocapsid protein in retroviruses.

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