Dataset Information

Prediction of Drug Side Effects with a Refined Negative Sample Selection Strategy.

ABSTRACT: Drugs are an important way to treat various diseases. However, they inevitably produce side effects, bringing great risks to human bodies and pharmaceutical companies. How to predict the side effects of drugs has become one of the essential problems in drug research. Designing efficient computational methods is an alternative way. Some studies paired the drug and side effect as a sample, thereby modeling the problem as a binary classification problem. However, the selection of negative samples is a key problem in this case. In this study, a novel negative sample selection strategy was designed for accessing high-quality negative samples. Such strategy applied the random walk with restart (RWR) algorithm on a chemical-chemical interaction network to select pairs of drugs and side effects, such that drugs were less likely to have corresponding side effects, as negative samples. Through several tests with a fixed feature extraction scheme and different machine-learning algorithms, models with selected negative samples produced high performance. The best model even yielded nearly perfect performance. These models had much higher performance than those without such strategy or with another selection strategy. Furthermore, it is not necessary to consider the balance of positive and negative samples under such a strategy.

SUBMITTER: Liang H

PROVIDER: S-EPMC7232712 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prediction of Drug Side Effects with a Refined Negative Sample Selection Strategy.

Liang Haiyan H Chen Lei L Zhao Xian X Zhang Xiaolin X

Computational and mathematical methods in medicine 20200509

Drugs are an important way to treat various diseases. However, they inevitably produce side effects, bringing great risks to human bodies and pharmaceutical companies. How to predict the side effects of drugs has become one of the essential problems in drug research. Designing efficient computational methods is an alternative way. Some studies paired the drug and side effect as a sample, thereby modeling the problem as a binary classification problem. However, the selection of negative samples i ...[more]

PMID: 32454877

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Project description:BACKGROUND:In silico prediction of potential drug side-effects is of crucial importance for drug development, since wet experimental identification of drug side-effects is expensive and time-consuming. Existing computational methods mainly focus on leveraging validated drug side-effect relations for the prediction. The performance is severely impeded by the lack of reliable negative training data. Thus, a method to select reliable negative samples becomes vital in the performance improvement. METHODS:Most of the existing computational prediction methods are essentially based on the assumption that similar drugs are inclined to share the same side-effects, which has given rise to remarkable performance. It is also rational to assume an inverse proposition that dissimilar drugs are less likely to share the same side-effects. Based on this inverse similarity hypothesis, we proposed a novel method to select highly-reliable negative samples for side-effect prediction. The first step of our method is to build a drug similarity integration framework to measure the similarity between drugs from different perspectives. This step integrates drug chemical structures, drug target proteins, drug substituents, and drug therapeutic information as features into a unified framework. Then, a similarity score between each candidate negative drug and validated positive drugs is calculated using the similarity integration framework. Those candidate negative drugs with lower similarity scores are preferentially selected as negative samples. Finally, both the validated positive drugs and the selected highly-reliable negative samples are used for predictions. RESULTS:The performance of the proposed method was evaluated on simulative side-effect prediction of 917 DrugBank drugs, comparing with four machine-learning algorithms. Extensive experiments show that the drug similarity integration framework has superior capability in capturing drug features, achieving much better performance than those based on a single type of drug property. Besides, the four machine-learning algorithms achieved significant improvement in macro-averaging F1-score (e.g., SVM from 0.655 to 0.898), macro-averaging precision (e.g., RBF from 0.592 to 0.828) and macro-averaging recall (e.g., KNN from 0.651 to 0.772) complimentarily attributed to the highly-reliable negative samples selected by the proposed method. CONCLUSIONS:The results suggest that the inverse similarity hypothesis and the integration of different drug properties are valuable for side-effect prediction. The selection of highly-reliable negative samples can also make significant contributions to the performance improvement.

Project description:Initial findings on genomic selection (GS) indicated substantial improvement for major traits, such as performance, and even successful selection for antagonistic traits. However, recent unofficial reports indicate an increased frequency of deterioration of secondary traits. This phenomenon may arise due to the mismatch between the accelerated selection process and resource allocation. Traits explicitly or implicitly accounted for by a selection index move toward the desired direction, whereas neglected traits change according to the genetic correlations with selected traits. Historically, the first stage of commercial genetic selection focused on production traits. After long-term selection, production traits improved, whereas fitness traits deteriorated, although this deterioration was partially compensated for by constantly improving management. Adding these fitness traits to the breeding objective and the used selection index also helped offset their decline while promoting long-term gains. Subsequently, the trend in observed fitness traits was a combination of a negative response due to genetic antagonism, positive response from inclusion in the selection index, and a positive effect of improving management. Under GS, the genetic trends accelerate, especially for well-recorded higher heritability traits, magnifying the negatively correlated responses for fitness traits. Then, the observed trend for fitness traits can become negative, especially because management modifications do not accelerate under GS. Additional deterioration can occur due to the rapid turnover of GS, as heritabilities for production traits can decline and the genetic antagonism between production and fitness traits can intensify. If the genetic parameters are not updated, the selection index will be inaccurate, and the intended gains will not occur. While the deterioration can accelerate for unrecorded or sparsely recorded fitness traits, GS can lead to an improvement for widely recorded fitness traits. In the context of GS, it is crucial to look for unexpected changes in relevant traits and take rapid steps to prevent further declines, especially in secondary traits. Changes can be anticipated by investigating the temporal dynamics of genetic parameters, especially genetic correlations. However, new methods are needed to estimate genetic parameters for the last generation with large amounts of genomic data.

Dataset Information

Prediction of Drug Side Effects with a Refined Negative Sample Selection Strategy.

Publications

Prediction of Drug Side Effects with a Refined Negative Sample Selection Strategy.

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