Nowadays,smart healthcare and biomedical research have marked a substantial growth rate in terms of their presence in the literature,computational approaches,and discoveries,owing to which a massive quantity of experi...Nowadays,smart healthcare and biomedical research have marked a substantial growth rate in terms of their presence in the literature,computational approaches,and discoveries,owing to which a massive quantity of experimental datasets was published and generated(Big Data)for describing and validating such novelties.Drug-drug interaction(DDI)significantly contributed to drug administration and development.It continues as the main obstacle in offering inexpensive and safe healthcare.It normally happens for patients with extensive medication,leading them to take many drugs simultaneously.DDI may cause side effects,either mild or severe health problems.This reduced victims’quality of life and increased hospital healthcare expenses by increasing their recovery time.Several efforts were made to formulate new methods for DDI prediction to overcome this issue.In this aspect,this study designs a new Spotted Hyena Optimizer Driven Deep Learning based Drug-Drug Interaction Prediction(SHODL-DDIP)model in a big data environment.In the presented SHODL-DDIP technique,the relativity and characteristics of the drugs can be identified from different sources for prediction.The input data is preprocessed at the primary level to improve its quality.Next,the salp swarm optimization algorithm(SSO)is used to select features.In this study,the deep belief network(DBN)model is exploited to predict the DDI accurately.The SHO algorithm is involved in improvising the DBN model’s predictive outcomes,showing the novelty of the work.The experimental result analysis of the SHODL-DDIP technique is tested using drug databases,and the results signified the improvements of the SHODLDDIP technique over other recent models in terms of different performance measures.展开更多
Recently,drug-drug cocrystal attracts more and more attention.It offers a low risk,low-cost but high reward route to new and better medicines and could improve the physiochemical and biopharmaceutical properties of a ...Recently,drug-drug cocrystal attracts more and more attention.It offers a low risk,low-cost but high reward route to new and better medicines and could improve the physiochemical and biopharmaceutical properties of a medicine by addition of a suitable therapeutically effective component without any chemical modification.Having so many advantages,to date,the reported drug-drug cocrystals are rare.Here we review the drug-drug cocrystals that reported in last decade and shed light on the opportunities and challenges for the development of drug-drug cocrystals.展开更多
BACKGROUND New direct-acting antivirals(DAAs)-based anti-hepatitis C virus(HCV)therapies are highly effective in patients with HCV infection.However,safety data are lacking regarding HCV treatment with DAAs and drugs ...BACKGROUND New direct-acting antivirals(DAAs)-based anti-hepatitis C virus(HCV)therapies are highly effective in patients with HCV infection.However,safety data are lacking regarding HCV treatment with DAAs and drugs for comorbidities.CASE SUMMARY Herein,we reported a case of HCV-infection in a 46-year-old man with benign prostatic hypertrophy.The patient received sofosbuvir/velpatasvir as well as methadone maintenance therapy for drug abuse.The viral load became negative at week 1 post treatment.He developed facial and bilateral lower extremity edema 48 h after starting receiving tamsulosin.Edema disappeared 10 d after treatment with oral furosemide and spironolactone.CONCLUSION In conclusion,this is the first case of an acute edema in the course of treatment with new DAAs,methadone and tamsulosin.These agents are useful in clinical management of patients with HCV infection,particularly in men with benign prostatic hypertrophy.Clinicians should be aware of potential drug-drug interactions in this subset of patients.展开更多
Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we anal...Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we analyzed all prescriptions (n = 1014) involving two or more drugs dispensed to the population (age range 4-85 years) from all pharmacies, clinics and hospitals. Data were stratified by age and sex, and frequency of common interacting drugs. Potential drug interactions were classified according to clinical relevance as significance of severity (types A: major, B: moderate, and C: minor) and documented evidence (types 1, 2, 3, and 4). Result and Discussion: The growing use of pharmacological agents means that drug interactions are of increasing interest for public health. Monitoring of potential drug interactions may improve the quality of drug prescribing and dispensing, and it might form a basis for education focused on appropriate prescribing. To make the manifestation of adverse interaction subside, management strategies must be exercised if two interacting drugs have to be taken with each other, involving: adjusting the dose of the object drug;spacing dosing times to avoid the interaction. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action they should take. Conclusion: It is unrealistic to expect clinicians to memorize the thousands of drug-drug interactions and their clinical significance, especially considering the rate of introduction of novel drugs and the escalating appreciation of the importance of pharmacogenomics. Reliable regularly updated decision support systems and information technology are necessary to help avert dangerous drug combinations.展开更多
Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP trans...Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP transporters. Several drug-drug interactions (DDIs) were noticed when protease inhibitors (PIs) coadministered with drugs metabolized by CYP3A4. The PIs are also potent mechanism based inhibitors, out which ritonavir is most potent. In the current study we evaluated in vitro (mouse and human liver microsomes) and in vivo DDIs of repaglinide with anti-HIV drugs. Out of the following tested drugs (Amprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Delavirdine, Maraviroc, Efavirenz, Nevirapine and Ketoconazole) Amprenavir (APV), Ritonavir (RTV) and Ketoconazole (KTZ) showed inhibition of OH-repaglinide formation in human and mouse liver microsomes. The positive reversible inhibitions were further tested for irreversible inhibitions where we didn’t observe any irreversible inhibitions. In vitro inhibitions were further evaluated in the in vivo pharmacokinetics (mouse) where repaglinide pharmacokinetics was altered by RTV and KTZ. The DDIs in both studies were very strong;the dose of repaglinide is reduced to 20 fold. In conclusion, there could be possible DDIs when RTV dosed with repaglinide;we have also demonstrated that mouse could be useful preclinical tool when used in conjunction with in vitro screening models for DDIs.展开更多
Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients ta...Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients take these agents simultaneously in the morning and the evening. The aim of this study was to examine the pharmacokinetics of sildenafil which was interfered with bosentan administration to ascertain whether these agents should be given concomitantly or separately. A two-way crossover study was conducted in 6 PAH patients with combination therapy of sildenafil and bosentan. Participants underwent the sequence of treatment phases: phase S (sildenafil administered 3 h before bosen-tan);phase B (bosentan administered 3 h before sildenafil);and phase C (administered concomitantly). Blood samples were collected on the last day of each phase. There was no significant difference in maximum plasma concentration or area under the plasma concentration-time curve (AUC0-8) between phase C and phase S (95.5 ± 24.8 vs. 72.9 ± 40.9 (p = 0.07), 209.7 ± 81.8 vs. 180.2 ± 126.4 (p = 0.24), respectively) or between phases C and B (87.8 ± 42.0 vs. 99.6 ± 33.9 (p = 0.59), 197.2 ± 88.2 vs. 240.7 ± 121.8 (p = 0.19), respectively) (ng/mL, mean ± standard deviation). Large intra-and inter-individual variability in sildenafil concentration was noted. The timing of administration of sildenafil and bosentan does not significantly influence the plasma concentration of sildenafil. Physicians do not need to be overly concerned about the timing of administration of these drugs to maximize the sildenafil concentration.展开更多
The direct acting antivirals(DAAs)are now the standard of care for hepatitis C virus(HCV)treatment with high and effective sustained virologic responserate(SVR)and great safety profile,including solid organ transplant...The direct acting antivirals(DAAs)are now the standard of care for hepatitis C virus(HCV)treatment with high and effective sustained virologic responserate(SVR)and great safety profile,including solid organ transplant patients.There are increasing reports showing DAAs are effective with high SVR rates and safety profile in kidney transplant recipients.There are reports on drug-drug interaction(DDI)between tacrolimus with DAAs.However,data remain lacking on potential DDIs between tacrolimus and DAA regimens and the management process.This case series reports three kidney transplant patients on tacrolimus who were successfully treated for HCV with multidisciplinary approach,although there was DDI between tacrolimus with sofosbuvir/velpatasvir and glecaprevir/pibrentasvir,which required tacrolimus dose adjustment to maintain therapeutic level during and after DAA treatment.Such DDIs should be aware of and closely monitored by pharmacist and physicians with tacrolimus dose adjustment as needed during and right after DAA treatment in post-kidney transplant patients.展开更多
AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical phar...AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.展开更多
The prediction of drug-drug interactions(DDIs)is a crucial task for drug safety research,and identifying potential DDIs helps us to explore the mechanism behind combinatorial therapy.Traditional wet chemical experimen...The prediction of drug-drug interactions(DDIs)is a crucial task for drug safety research,and identifying potential DDIs helps us to explore the mechanism behind combinatorial therapy.Traditional wet chemical experiments for DDI are cumbersome and time-consuming,and are too small in scale,limiting the efficiency of DDI predictions.Therefore,it is particularly crucial to develop improved computational methods for detecting drug interactions.With the development of deep learning,several computational models based on deep learning have been proposed for DDI prediction.In this review,we summarized the high-quality DDI prediction methods based on deep learning in recent years,and divided them into four categories:neural network-based methods,graph neural network-based methods,knowledge graph-based methods,and multimodal-based methods.Furthermore,we discuss the challenges of existing methods and future potential perspectives.This review reveals that deep learning can significantly improve DDI prediction performance compared to traditional machine learning.Deep learning models can scale to large-scale datasets and accept multiple data types as input,thus making DDI predictions more efficient and accurate.展开更多
Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact ...Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively,their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure.Methods:In this paper,we develop DeepDrug,a deep learning framework for overcoming the above limitation by using residual graph convolutional networks(Res-GCNs)and convolutional networks(CNNs)to learn the comprehensive structure-and sequence-based representations of drugs and proteins.Results:DeepDrug outperforms state-of-the-art methods in a series of systematic experiments,including binary-class DDIs,multi-class/multi-label DDIs,binary-class DTIs classification and DTIs regression tasks.Furthermore,we visualize the structural features learned by DeepDrug Res-GCN module,which displays compatible and accordant patterns in chemical properties and drug categories,providing additional evidence to support the strong predictive power of DeepDrug.Ultimately,we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2,where 7 out of 10 top-ranked drugs are reported to be repurposed to potentially treat coronavirus disease 2019(COVID-19).Conclusions:To sum up,we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations.展开更多
文摘Nowadays,smart healthcare and biomedical research have marked a substantial growth rate in terms of their presence in the literature,computational approaches,and discoveries,owing to which a massive quantity of experimental datasets was published and generated(Big Data)for describing and validating such novelties.Drug-drug interaction(DDI)significantly contributed to drug administration and development.It continues as the main obstacle in offering inexpensive and safe healthcare.It normally happens for patients with extensive medication,leading them to take many drugs simultaneously.DDI may cause side effects,either mild or severe health problems.This reduced victims’quality of life and increased hospital healthcare expenses by increasing their recovery time.Several efforts were made to formulate new methods for DDI prediction to overcome this issue.In this aspect,this study designs a new Spotted Hyena Optimizer Driven Deep Learning based Drug-Drug Interaction Prediction(SHODL-DDIP)model in a big data environment.In the presented SHODL-DDIP technique,the relativity and characteristics of the drugs can be identified from different sources for prediction.The input data is preprocessed at the primary level to improve its quality.Next,the salp swarm optimization algorithm(SSO)is used to select features.In this study,the deep belief network(DBN)model is exploited to predict the DDI accurately.The SHO algorithm is involved in improvising the DBN model’s predictive outcomes,showing the novelty of the work.The experimental result analysis of the SHODL-DDIP technique is tested using drug databases,and the results signified the improvements of the SHODLDDIP technique over other recent models in terms of different performance measures.
文摘Recently,drug-drug cocrystal attracts more and more attention.It offers a low risk,low-cost but high reward route to new and better medicines and could improve the physiochemical and biopharmaceutical properties of a medicine by addition of a suitable therapeutically effective component without any chemical modification.Having so many advantages,to date,the reported drug-drug cocrystals are rare.Here we review the drug-drug cocrystals that reported in last decade and shed light on the opportunities and challenges for the development of drug-drug cocrystals.
基金Supported by the National Natural Science Foundation of China,No.81701632Shanxi Province Social Development Project,No.2018SF-269.
文摘BACKGROUND New direct-acting antivirals(DAAs)-based anti-hepatitis C virus(HCV)therapies are highly effective in patients with HCV infection.However,safety data are lacking regarding HCV treatment with DAAs and drugs for comorbidities.CASE SUMMARY Herein,we reported a case of HCV-infection in a 46-year-old man with benign prostatic hypertrophy.The patient received sofosbuvir/velpatasvir as well as methadone maintenance therapy for drug abuse.The viral load became negative at week 1 post treatment.He developed facial and bilateral lower extremity edema 48 h after starting receiving tamsulosin.Edema disappeared 10 d after treatment with oral furosemide and spironolactone.CONCLUSION In conclusion,this is the first case of an acute edema in the course of treatment with new DAAs,methadone and tamsulosin.These agents are useful in clinical management of patients with HCV infection,particularly in men with benign prostatic hypertrophy.Clinicians should be aware of potential drug-drug interactions in this subset of patients.
文摘Objective: To analyze the use of all subsidized prescription drugs including their use of drug combination generally accepted as carrying a risk of severe interactions. Methodology: In a cross sectional study, we analyzed all prescriptions (n = 1014) involving two or more drugs dispensed to the population (age range 4-85 years) from all pharmacies, clinics and hospitals. Data were stratified by age and sex, and frequency of common interacting drugs. Potential drug interactions were classified according to clinical relevance as significance of severity (types A: major, B: moderate, and C: minor) and documented evidence (types 1, 2, 3, and 4). Result and Discussion: The growing use of pharmacological agents means that drug interactions are of increasing interest for public health. Monitoring of potential drug interactions may improve the quality of drug prescribing and dispensing, and it might form a basis for education focused on appropriate prescribing. To make the manifestation of adverse interaction subside, management strategies must be exercised if two interacting drugs have to be taken with each other, involving: adjusting the dose of the object drug;spacing dosing times to avoid the interaction. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action they should take. Conclusion: It is unrealistic to expect clinicians to memorize the thousands of drug-drug interactions and their clinical significance, especially considering the rate of introduction of novel drugs and the escalating appreciation of the importance of pharmacogenomics. Reliable regularly updated decision support systems and information technology are necessary to help avert dangerous drug combinations.
文摘Repaglinide is type 2 short acting anti-diabetic drug which is primarily metabolized by CYP2C8 and CYP3A4 and is also a substrate of influx transporter OATP1B1. HIV drugs are potent inhibitors of CYP3A4 and OATP transporters. Several drug-drug interactions (DDIs) were noticed when protease inhibitors (PIs) coadministered with drugs metabolized by CYP3A4. The PIs are also potent mechanism based inhibitors, out which ritonavir is most potent. In the current study we evaluated in vitro (mouse and human liver microsomes) and in vivo DDIs of repaglinide with anti-HIV drugs. Out of the following tested drugs (Amprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Delavirdine, Maraviroc, Efavirenz, Nevirapine and Ketoconazole) Amprenavir (APV), Ritonavir (RTV) and Ketoconazole (KTZ) showed inhibition of OH-repaglinide formation in human and mouse liver microsomes. The positive reversible inhibitions were further tested for irreversible inhibitions where we didn’t observe any irreversible inhibitions. In vitro inhibitions were further evaluated in the in vivo pharmacokinetics (mouse) where repaglinide pharmacokinetics was altered by RTV and KTZ. The DDIs in both studies were very strong;the dose of repaglinide is reduced to 20 fold. In conclusion, there could be possible DDIs when RTV dosed with repaglinide;we have also demonstrated that mouse could be useful preclinical tool when used in conjunction with in vitro screening models for DDIs.
文摘Sildenafil and bosentan are often co-administered for pulmonary arterial hypertension (PAH) treatment. The plasma concentration of sildenafil can be decreased by half if co-administered with bosentan. Many patients take these agents simultaneously in the morning and the evening. The aim of this study was to examine the pharmacokinetics of sildenafil which was interfered with bosentan administration to ascertain whether these agents should be given concomitantly or separately. A two-way crossover study was conducted in 6 PAH patients with combination therapy of sildenafil and bosentan. Participants underwent the sequence of treatment phases: phase S (sildenafil administered 3 h before bosen-tan);phase B (bosentan administered 3 h before sildenafil);and phase C (administered concomitantly). Blood samples were collected on the last day of each phase. There was no significant difference in maximum plasma concentration or area under the plasma concentration-time curve (AUC0-8) between phase C and phase S (95.5 ± 24.8 vs. 72.9 ± 40.9 (p = 0.07), 209.7 ± 81.8 vs. 180.2 ± 126.4 (p = 0.24), respectively) or between phases C and B (87.8 ± 42.0 vs. 99.6 ± 33.9 (p = 0.59), 197.2 ± 88.2 vs. 240.7 ± 121.8 (p = 0.19), respectively) (ng/mL, mean ± standard deviation). Large intra-and inter-individual variability in sildenafil concentration was noted. The timing of administration of sildenafil and bosentan does not significantly influence the plasma concentration of sildenafil. Physicians do not need to be overly concerned about the timing of administration of these drugs to maximize the sildenafil concentration.
文摘The direct acting antivirals(DAAs)are now the standard of care for hepatitis C virus(HCV)treatment with high and effective sustained virologic responserate(SVR)and great safety profile,including solid organ transplant patients.There are increasing reports showing DAAs are effective with high SVR rates and safety profile in kidney transplant recipients.There are reports on drug-drug interaction(DDI)between tacrolimus with DAAs.However,data remain lacking on potential DDIs between tacrolimus and DAA regimens and the management process.This case series reports three kidney transplant patients on tacrolimus who were successfully treated for HCV with multidisciplinary approach,although there was DDI between tacrolimus with sofosbuvir/velpatasvir and glecaprevir/pibrentasvir,which required tacrolimus dose adjustment to maintain therapeutic level during and after DAA treatment.Such DDIs should be aware of and closely monitored by pharmacist and physicians with tacrolimus dose adjustment as needed during and right after DAA treatment in post-kidney transplant patients.
文摘AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.
基金National Natural Science Foundationof China,Grant/Award Number:62102158Fundamental Research Fundsforthe Central Universities,Grant/Award Number:2662022JC004+1 种基金2021 Foshan Support Project for Promoting the Development of University Scientific and Technological Achievements ServiceIndustry,Grant/Award Number:2021DZXX05Huazhong Agricultural University Scientific Technological Selfinnovation Foundation。
文摘The prediction of drug-drug interactions(DDIs)is a crucial task for drug safety research,and identifying potential DDIs helps us to explore the mechanism behind combinatorial therapy.Traditional wet chemical experiments for DDI are cumbersome and time-consuming,and are too small in scale,limiting the efficiency of DDI predictions.Therefore,it is particularly crucial to develop improved computational methods for detecting drug interactions.With the development of deep learning,several computational models based on deep learning have been proposed for DDI prediction.In this review,we summarized the high-quality DDI prediction methods based on deep learning in recent years,and divided them into four categories:neural network-based methods,graph neural network-based methods,knowledge graph-based methods,and multimodal-based methods.Furthermore,we discuss the challenges of existing methods and future potential perspectives.This review reveals that deep learning can significantly improve DDI prediction performance compared to traditional machine learning.Deep learning models can scale to large-scale datasets and accept multiple data types as input,thus making DDI predictions more efficient and accurate.
基金fundings from National Key Research and Development Program of China(Nos.2021YFF1200902 and 2020YFA0712402)National Natural Science Foundation of China(Nos.62273194,61873141,61721003 and 62003178).
文摘Background:Computational approaches for accurate prediction of drug interactions,such as drug-drug interactions(DDIs)and drug-target interactions(DTIs),are highly demanded for biochemical researchers.Despite the fact that many methods have been proposed and developed to predict DDIs and DTIs respectively,their success is still limited due to a lack of systematic evaluation of the intrinsic properties embedded in the corresponding chemical structure.Methods:In this paper,we develop DeepDrug,a deep learning framework for overcoming the above limitation by using residual graph convolutional networks(Res-GCNs)and convolutional networks(CNNs)to learn the comprehensive structure-and sequence-based representations of drugs and proteins.Results:DeepDrug outperforms state-of-the-art methods in a series of systematic experiments,including binary-class DDIs,multi-class/multi-label DDIs,binary-class DTIs classification and DTIs regression tasks.Furthermore,we visualize the structural features learned by DeepDrug Res-GCN module,which displays compatible and accordant patterns in chemical properties and drug categories,providing additional evidence to support the strong predictive power of DeepDrug.Ultimately,we apply DeepDrug to perform drug repositioning on the whole DrugBank database to discover the potential drug candidates against SARS-CoV-2,where 7 out of 10 top-ranked drugs are reported to be repurposed to potentially treat coronavirus disease 2019(COVID-19).Conclusions:To sum up,we believe that DeepDrug is an efficient tool in accurate prediction of DDIs and DTIs and provides a promising insight in understanding the underlying mechanism of these biochemical relations.