The Discovery of New Drug-Target Interactions for Breast Cancer Treatment.

Abstract

Drug-target interaction (DTIs) prediction plays a vital role in probing new targets for breast cancer research. Considering the multifaceted challenges associated with experimental methods identifying DTIs, the in silico prediction of such interactions merits exploration. In this study, we develop a feature-based method to infer unknown DTIs, called PsePDC-DTIs, which fuses information regarding protein sequences extracted by pseudo-position specific scoring matrix (PsePSSM), detrended cross-correlation analysis coefficient (DCCA coefficient), and an FP2 format molecular fingerprint descriptor of drug compounds. In addition, the synthetic minority oversampling technique (SMOTE) is employed for dealing with the imbalanced data after Lasso dimensionality reduction. Then, the processed feature vectors are put into a random forest classifier to perform DTIs predictions on four gold standard datasets, including nuclear receptors (NR), G-protein-coupled receptors (GPCR), ion channels (IC), and enzymes (E). Furthermore, we explore new targets for breast cancer treatment using its risk genes identified from large-scale genome-wide genetic studies using PsePDC-DTIs. Through five-fold cross-validation, the average values of accuracy in NR, GPCR, IC, and E datasets are 95.28%, 96.19%, 96.74%, and 98.22%, respectively. The PsePDC-DTIs model provides us with 10 potential DTIs for breast cancer treatment, among which erlotinib (DB00530) and FGFR2 (hsa2263), caffeine (DB00201) and KCNN4 (hsa3783), as well as afatinib (DB08916) and FGFR2 (hsa2263) are found with direct or inferred evidence. The PsePDC-DTIs model has achieved good prediction results, establishing the validity and superiority of the proposed method.

• Authors: Jiali Song, Zhenyi Xu, Lei Cao, Meng Wang, Yan Hou, Kang Li
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 26 Issue 24 (Dec 10 2021) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 34946556 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Enzymes
• Ion Channels
• Receptors, Cytoplasmic and Nuclear
• Receptors, G-Protein-Coupled

Topics

• Algorithms
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, genetics, metabolism)
• Drug Discovery
• Enzymes (genetics, metabolism)
• Female
• Humans
• Ion Channels (antagonists & inhibitors, genetics, metabolism)
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, genetics, metabolism)
• Receptors, G-Protein-Coupled (antagonists & inhibitors, genetics, metabolism)