Dataset Information

Identification of Novel Antibacterials Using Machine Learning Techniques.

ABSTRACT: Many pharmaceutical companies are avoiding the development of novel antibacterials due to a range of rational reasons and the high risk of failure. However, there is an urgent need for novel antibiotics especially against resistant bacterial strains. Available in silico models suffer from many drawbacks and, therefore, are not applicable for scoring novel molecules with high structural diversity by their antibacterial potency. Considering this, the overall aim of this study was to develop an efficient in silico model able to find compounds that have plenty of chances to exhibit antibacterial activity. Based on a proprietary screening campaign, we have accumulated a representative dataset of more than 140,000 molecules with antibacterial activity against Escherichia coli assessed in the same assay and under the same conditions. This intriguing set has no analogue in the scientific literature. We applied six in silico techniques to mine these data. For external validation, we used 5,000 compounds with low similarity towards training samples. The antibacterial activity of the selected molecules against E. coli was assessed using a comprehensive biological study. Kohonen-based nonlinear mapping was used for the first time and provided the best predictive power (av. 75.5%). Several compounds showed an outstanding antibacterial potency and were identified as translation machinery inhibitors in vitro and in vivo. For the best compounds, MIC and CC50 values were determined to allow us to estimate a selectivity index (SI). Many active compounds have a robust IP position.

SUBMITTER: Ivanenkov YA

PROVIDER: S-EPMC6719509 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of Novel Antibacterials Using Machine Learning Techniques.

Ivanenkov Yan A YA Zhavoronkov Alex A Yamidanov Renat S RS Osterman Ilya A IA Sergiev Petr V PV Aladinskiy Vladimir A VA Aladinskaya Anastasia V AV Terentiev Victor A VA Veselov Mark S MS Ayginin Andrey A AA Kartsev Victor G VG Skvortsov Dmitry A DA Chemeris Alexey V AV Baimiev Alexey Kh AK Sofronova Alina A AA Malyshev Alexander S AS Filkov Gleb I GI Bezrukov Dmitry S DS Zagribelnyy Bogdan A BA Putin Evgeny O EO Puchinina Maria M MM Dontsova Olga A OA

Frontiers in pharmacology 20190827

Many pharmaceutical companies are avoiding the development of novel antibacterials due to a range of rational reasons and the high risk of failure. However, there is an urgent need for novel antibiotics especially against resistant bacterial strains. Available <i>in silico</i> models suffer from many drawbacks and, therefore, are not applicable for scoring novel molecules with high structural diversity by their antibacterial potency. Considering this, the overall aim of this study was to develop ...[more]

PMID: 31507413

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Project description:BACKGROUND:With the global spread of multidrug resistance in pathogenic microbes, infectious diseases emerge as a key public health concern of the recent time. Identification of host genes associated with infectious diseases will improve our understanding about the mechanisms behind their development and help to identify novel therapeutic targets. RESULTS:We developed a machine learning techniques-based classification approach to identify infectious disease-associated host genes by integrating sequence and protein interaction network features. Among different methods, Deep Neural Networks (DNN) model with 16 selected features for pseudo-amino acid composition (PAAC) and network properties achieved the highest accuracy of 86.33% with sensitivity of 85.61% and specificity of 86.57%. The DNN classifier also attained an accuracy of 83.33% on a blind dataset and a sensitivity of 83.1% on an independent dataset. Furthermore, to predict unknown infectious disease-associated host genes, we applied the proposed DNN model to all reviewed proteins from the database. Seventy-six out of 100 highly-predicted infectious disease-associated genes from our study were also found in experimentally-verified human-pathogen protein-protein interactions (PPIs). Finally, we validated the highly-predicted infectious disease-associated genes by disease and gene ontology enrichment analysis and found that many of them are shared by one or more of the other diseases, such as cancer, metabolic and immune related diseases. CONCLUSIONS:To the best of our knowledge, this is the first computational method to identify infectious disease-associated host genes. The proposed method will help large-scale prediction of host genes associated with infectious-diseases. However, our results indicated that for small datasets, advanced DNN-based method does not offer significant advantage over the simpler supervised machine learning techniques, such as Support Vector Machine (SVM) or Random Forest (RF) for the prediction of infectious disease-associated host genes. Significant overlap of infectious disease with cancer and metabolic disease on disease and gene ontology enrichment analysis suggests that these diseases perturb the functions of the same cellular signaling pathways and may be treated by drugs that tend to reverse these perturbations. Moreover, identification of novel candidate genes associated with infectious diseases would help us to explain disease pathogenesis further and develop novel therapeutics.

Project description:ImportanceCompetence in cataract surgery is a public health necessity, and videos of cataract surgery are routinely available to educators and trainees but currently are of limited use in training. Machine learning and deep learning techniques can yield tools that efficiently segment videos of cataract surgery into constituent phases for subsequent automated skill assessment and feedback.ObjectiveTo evaluate machine learning and deep learning algorithms for automated phase classification of manually presegmented phases in videos of cataract surgery.Design, setting, and participantsThis was a cross-sectional study using a data set of videos from a convenience sample of 100 cataract procedures performed by faculty and trainee surgeons in an ophthalmology residency program from July 2011 to December 2017. Demographic characteristics for surgeons and patients were not captured. Ten standard labels in the procedure and 14 instruments used during surgery were manually annotated, which served as the ground truth.ExposuresFive algorithms with different input data: (1) a support vector machine input with cross-sectional instrument label data; (2) a recurrent neural network (RNN) input with a time series of instrument labels; (3) a convolutional neural network (CNN) input with cross-sectional image data; (4) a CNN-RNN input with a time series of images; and (5) a CNN-RNN input with time series of images and instrument labels. Each algorithm was evaluated with 5-fold cross-validation.Main outcomes and measuresAccuracy, area under the receiver operating characteristic curve, sensitivity, specificity, and precision.ResultsUnweighted accuracy for the 5 algorithms ranged between 0.915 and 0.959. Area under the receiver operating characteristic curve for the 5 algorithms ranged between 0.712 and 0.773, with small differences among them. The area under the receiver operating characteristic curve for the image-only CNN-RNN (0.752) was significantly greater than that of the CNN with cross-sectional image data (0.712) (difference, -0.040; 95% CI, -0.049 to -0.033) and the CNN-RNN with images and instrument labels (0.737) (difference, 0.016; 95% CI, 0.014 to 0.018). While specificity was uniformly high for all phases with all 5 algorithms (range, 0.877 to 0.999), sensitivity ranged between 0.005 (95% CI, 0.000 to 0.015) for the support vector machine for wound closure (corneal hydration) and 0.974 (95% CI, 0.957 to 0.991) for the RNN for main incision. Precision ranged between 0.283 and 0.963.Conclusions and relevanceTime series modeling of instrument labels and video images using deep learning techniques may yield potentially useful tools for the automated detection of phases in cataract surgery procedures.

Dataset Information

Identification of Novel Antibacterials Using Machine Learning Techniques.

Publications

Identification of Novel Antibacterials Using Machine Learning Techniques.

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