The application of machine learning techniques to innovative antibacterial discovery and development.

INTRODUCTION: After the initial wave of antibiotic discovery, few novel classes of antibiotics have emerged, with the latest dating back to the 1980's. Furthermore, the pace of antibiotic drug discovery is unable to keep up with the increasing prevalence of antibiotic drug resistance. However, the increasing amount of available data promotes the use of machine learning techniques (MLT) in drug discovery projects (e.g. construction of regression/classification models and ranking/virtual screening of compounds). AREAS COVERED: In this review, the authors cover some of the applications of MLT in medicinal chemistry, focusing on the development of new antibiotics, the prediction of resistance and its mechanisms. The aim of this review is to illustrate the main advantages and disadvantages and the major trends from studies over the past 5 years. EXPERT OPINION: The application of MLT to antibacterial drug discovery can aid the selection of new and potent lead compounds, with desirable pharmacokinetic and toxic profiles for further optimization. The increasing volume of available data along with the constant improvement in computational power and algorithms has meant that we are experiencing a transition in the way we face modern issues such as drug resistance, where our decisions are data-driven and experiments can be focused by data-suggested hypotheses.

Advances with support vector machines for novel drug discovery.

INTRODUCTION: Novel drug discovery remains an enormous challenge, with various computer-aided drug design (CADD) approaches having been widely employed for this purpose. CADD, specifically the commonly used support vector machines (SVMs), can employ machine learning techniques. SVMs and their variations offer numerous drug discovery applications, which range from the classification of substances (as active or inactive) to the construction of regression models and the ranking/virtual screening of databased compounds. Areas covered: Herein, the authors consider some of the applications of SVMs in medicinal chemistry, illustrating their main advantages and disadvantages, as well as trends in their utilization, via the available published literature. The aim of this review is to provide an up-to-date review of the recent applications of SVMs in drug discovery as described by the literature, thereby highlighting their strengths, weaknesses, and future challenges. Expert opinion: Techniques based on SVMs are considered as powerful approaches in early drug discovery. The ability of SVMs to classify active or inactive compounds has enabled the prioritization of substances for virtual screening. Indeed, one of the main advantages of SVMs is related to their potential in the analysis of nonlinear problems. However, despite successes in employing SVMs, the challenges of improving accuracy remain.

Applying machine learning techniques for ADME-Tox prediction: a review.

INTRODUCTION: Pharmacokinetics involves the study of absorption, distribution, metabolism, excretion and toxicity of xenobiotics (ADME-Tox). In this sense, the ADME-Tox profile of a bioactive compound can impact its efficacy and safety. Moreover, efficacy and safety were considered some of the major causes of clinical failures in the development of new chemical entities. In this context, machine learning (ML) techniques have been often used in ADME-Tox studies due to the existence of compounds with known pharmacokinetic properties available for generating predictive models. AREAS COVERED: This review examines the growth in the use of some ML techniques in ADME-Tox studies, in particular supervised and unsupervised techniques. Also, some critical points (e.g., size of the data set and type of output variable) must be considered during the generation of models that relate ADME-Tox properties and biological activity. EXPERT OPINION: ML techniques have been successfully employed in pharmacokinetic studies, helping the complex process of designing new drug candidates from the use of reliable ML models. An application of this procedure would be the prediction of ADME-Tox properties from studies of quantitative structure-activity relationships or the discovery of new compounds from a virtual screening using filters based on results obtained from ML techniques.