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Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

Zhao F, Guo X, Wang Y, Liu J, Lee WH, Zhang Y - PLoS ONE (2014)

Bottom Line: The discovery of new drugs requires the development of improved animal models for drug testing.The Chinese tree shrew is considered to be a realistic candidate model.Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, PR China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, PR China.

ABSTRACT
The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

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Performance of drug targets in the tree shrew.(A) ROC curves for predicted drug targets indicating high performance. (B) Comparison of tree shrew drug scores to those of human and mouse orthologs. The plot depicts the top 100 tree shrew drug scores.
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pone-0104191-g004: Performance of drug targets in the tree shrew.(A) ROC curves for predicted drug targets indicating high performance. (B) Comparison of tree shrew drug scores to those of human and mouse orthologs. The plot depicts the top 100 tree shrew drug scores.

Mentions: To evaluate our predictions, the predictor performance was measured using a receiver operating curve (ROC). Drug Bank targets were treated as the reference standard. As shown in Figure 4A, the AUC (area under the ROC curve) was attained for more than 80% of the potential drug targets in the tree shrew. Comparisons were then performed between the drug scores of these drug targets and the scores of their human and mouse orthologs (Table S9 in File S1). The top 100 ranked drug targets are shown in Figure 4B. Many of the tree shrew drug targets had higher scores than their mouse orthologs, which were approximately equal to those of their human orthologs (Figure 4B). Among the predicted drug targets in the tree shrew, approximately 57.5% of proteins had higher drug scores than their mouse orthologs. In addition, more than 17% of drug targets in the tree shrew had drug scores comparable to those of their mouse orthologs. These results indicate the similar suitability of the tree shrew and the mouse as drug testing models for depression and various cancers.


Drug target mining and analysis of the Chinese tree shrew for pharmacological testing.

Zhao F, Guo X, Wang Y, Liu J, Lee WH, Zhang Y - PLoS ONE (2014)

Performance of drug targets in the tree shrew.(A) ROC curves for predicted drug targets indicating high performance. (B) Comparison of tree shrew drug scores to those of human and mouse orthologs. The plot depicts the top 100 tree shrew drug scores.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126716&req=5

pone-0104191-g004: Performance of drug targets in the tree shrew.(A) ROC curves for predicted drug targets indicating high performance. (B) Comparison of tree shrew drug scores to those of human and mouse orthologs. The plot depicts the top 100 tree shrew drug scores.
Mentions: To evaluate our predictions, the predictor performance was measured using a receiver operating curve (ROC). Drug Bank targets were treated as the reference standard. As shown in Figure 4A, the AUC (area under the ROC curve) was attained for more than 80% of the potential drug targets in the tree shrew. Comparisons were then performed between the drug scores of these drug targets and the scores of their human and mouse orthologs (Table S9 in File S1). The top 100 ranked drug targets are shown in Figure 4B. Many of the tree shrew drug targets had higher scores than their mouse orthologs, which were approximately equal to those of their human orthologs (Figure 4B). Among the predicted drug targets in the tree shrew, approximately 57.5% of proteins had higher drug scores than their mouse orthologs. In addition, more than 17% of drug targets in the tree shrew had drug scores comparable to those of their mouse orthologs. These results indicate the similar suitability of the tree shrew and the mouse as drug testing models for depression and various cancers.

Bottom Line: The discovery of new drugs requires the development of improved animal models for drug testing.The Chinese tree shrew is considered to be a realistic candidate model.Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, PR China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, PR China.

ABSTRACT
The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.

Show MeSH
Related in: MedlinePlus