Multi-label classification and features investigation of antimicrobial peptides with various functional classes.

The challenge of drug-resistant bacteria to global public health has led to increased attention on antimicrobial peptides (AMPs) as a targeted therapeutic alternative with a lower risk of resistance. However, high production costs and limitations in functional class prediction have hindered progress in this field. In this study, we used multi-label classifiers with binary relevance and algorithm adaptation techniques to predict different functions of AMPs across a wide range of pathogen categories, including bacteria, mammalian cells, fungi, viruses, and cancer cells. Our classifiers attained promising AUC scores varying from 0.8492 to 0.9126 on independent testing data. Forward feature selection identified sequence order and charge as critical, with specific amino acids (C and E) as discriminative. These findings provide valuable insights for the design of antimicrobial peptides (AMPs) with multiple functionalities, thus contributing to the broader effort to combat drug-resistant pathogens.

A risk assessment framework for multidrug-resistant Staphylococcus aureus using machine learning and mass spectrometry technology.

The emergence of multidrug-resistant bacteria is a critical global crisis that poses a serious threat to public health, particularly with the rise of multidrug-resistant Staphylococcus aureus. Accurate assessment of drug resistance is essential for appropriate treatment and prevention of transmission of these deadly pathogens. Early detection of drug resistance in patients is critical for providing timely treatment and reducing the spread of multidrug-resistant bacteria. This study aims to develop a novel risk assessment framework for S. aureus that can accurately determine the resistance to multiple antibiotics. The comprehensive 7-year study involved ˃20 000 isolates with susceptibility testing profiles of six antibiotics. By incorporating mass spectrometry and machine learning, the study was able to predict the susceptibility to four different antibiotics with high accuracy. To validate the accuracy of our models, we externally tested on an independent cohort and achieved impressive results with an area under the receiver operating characteristic curve of 0. 94, 0.90, 0.86 and 0.91, and an area under the precision-recall curve of 0.93, 0.87, 0.87 and 0.81, respectively, for oxacillin, clindamycin, erythromycin and trimethoprim-sulfamethoxazole. In addition, the framework evaluated the level of multidrug resistance of the isolates by using the predicted drug resistance probabilities, interpreting them in the context of a multidrug resistance risk score and analyzing the performance contribution of different sample groups. The results of this study provide an efficient method for early antibiotic decision-making and a better understanding of the multidrug resistance risk of S. aureus.

Data-Driven Two-Stage Framework for Identification and Characterization of Different Antibiotic-Resistant Escherichia coli Isolates Based on Mass Spectrometry Data.

In clinical microbiology, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is frequently employed for rapid microbial identification. However, rapid identification of antimicrobial resistance (AMR) in Escherichia coli based on a large amount of MALDI-TOF MS data has not yet been reported. This may be because building a prediction model to cover all E. coli isolates would be challenging given the high diversity of the E. coli population. This study aimed to develop a MALDI-TOF MS-based, data-driven, two-stage framework for characterizing different AMRs in E. coli. Specifically, amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM) were used. In the first stage, we split the data into two groups based on informative peaks according to the importance of the random forest. In the second stage, prediction models were constructed using four different machine learning algorithms-logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). The findings demonstrate that XGBoost outperformed the other four machine learning models. The values of the area under the receiver operating characteristic curve were 0.62, 0.72, 0.87, 0.72, and 0.72 for AMC, CAZ, CIP, CRO, and CXM, respectively. This implies that a data-driven, two-stage framework could improve accuracy by approximately 2.8%. As a result, we developed AMR prediction models for E. coli using a data-driven two-stage framework, which is promising for assisting physicians in making decisions. Further, the analysis of informative peaks in future studies could potentially reveal new insights. IMPORTANCE Based on a large amount of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) clinical data, comprising 37,918 Escherichia coli isolates, a data-driven two-stage framework was established to evaluate the antimicrobial resistance of E. coli. Five antibiotics, including amoxicillin (AMC), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), and cefuroxime (CXM), were considered for the two-stage model training, and the values of the area under the receiver operating characteristic curve (AUC) were 0.62 for AMC, 0.72 for CAZ, 0.87 for CIP, 0.72 for CRO, and 0.72 for CXM. Further investigations revealed that the informative peak m/z 9714 appeared with some important peaks at m/z 6809, m/z 7650, m/z 10534, and m/z 11783 for CIP and at m/z 6809, m/z 10475, and m/z 8447 for CAZ, CRO, and CXM. This framework has the potential to improve the accuracy by approximately 2.8%, indicating a promising potential for further research.

Towards Accurate Identification of Antibiotic-Resistant Pathogens through the Ensemble of Multiple Preprocessing Methods Based on MALDI-TOF Spectra.

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been used to identify microorganisms and predict antibiotic resistance. The preprocessing method for the MS spectrum is key to extracting critical information from complicated MS spectral data. Different preprocessing methods yield different data, and the optimal approach is unclear. In this study, we adopted an ensemble of multiple preprocessing methods--FlexAnalysis, MALDIquant, and continuous wavelet transform-based methods--to detect peaks and build machine learning classifiers, including logistic regressions, naïve Bayes classifiers, random forests, and a support vector machine. The aim was to identify antibiotic resistance in Acinetobacter baumannii, Acinetobacter nosocomialis, Enterococcus faecium, and Group B Streptococci (GBS) based on MALDI-TOF MS spectra collected from two branches of a referral tertiary medical center. The ensemble method was compared with the individual methods. Random forest models built with the data preprocessed by the ensemble method outperformed individual preprocessing methods and achieved the highest accuracy, with values of 84.37% (A. baumannii), 90.96% (A. nosocomialis), 78.54% (E. faecium), and 70.12% (GBS) on independent testing datasets. Through feature selection, important peaks related to antibiotic resistance could be detected from integrated information. The prediction model can provide an opinion for clinicians. The discriminative peaks enabling better prediction performance can provide a reference for further investigation of the resistance mechanism.

Efficiently Predicting Vancomycin Resistance of Enterococcus Faecium From MALDI-TOF MS Spectra Using a Deep Learning-Based Approach.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has recently become a useful analytical approach for microbial identification. The presence and absence of specific peaks on MS spectra are commonly used to identify the bacterial species and predict antibiotic-resistant strains. However, the conventional approach using few single peaks would result in insufficient prediction power without using complete information of whole MS spectra. In the past few years, machine learning algorithms have been successfully applied to analyze the MALDI-TOF MS peaks pattern for rapid strain typing. In this study, we developed a convolutional neural network (CNN) method to deal with the complete information of MALDI-TOF MS spectra for detecting Enterococcus faecium, which is one of the leading pathogens in the world. We developed a CNN model to rapidly and accurately predict vancomycin-resistant Enterococcus faecium (VREfm) samples from the whole mass spectra profiles of clinical samples. The CNN models demonstrated good classification performances with the average area under the receiver operating characteristic curve (AUROC) of 0.887 when using external validation data independently. Additionally, we employed the score-class activation mapping (CAM) method to identify the important features of our CNN models and found some discriminative signals that can substantially contribute to detecting the ion of resistance. This study not only utilized the complete information of MALTI-TOF MS data directly but also provided a practical means for rapid detection of VREfm using a deep learning algorithm.

Rapid Antibiotic Resistance Serial Prediction in Staphylococcus aureus Based on Large-Scale MALDI-TOF Data by Applying XGBoost in Multi-Label Learning.

Multidrug resistance has become a phenotype that commonly exists among Staphylococcus aureus and is a serious concern for infection treatment. Nowadays, to detect the antibiotic susceptibility, antibiotic testing is generated based on the level of genomic for cure decision consuming huge of time and labor, while matrix-assisted laser desorption-ionization (MALDI) time-of-flight mass spectrometry (TOF/MS) shows its possibility in high-speed and effective detection on the level of proteomic. In this study, on the basis of MALDI-TOF spectra data of discovery cohort with 26,852 samples and replication cohort with 4,963 samples from Taiwan area and their corresponding susceptibilities to oxacillin and clindamycin, a multi-label prediction model against double resistance using Lowest Power set ensemble with XGBoost is constructed for rapid susceptibility prediction. With the output of serial susceptibility prediction, the model performance can realize 77% of accuracy for the serial prediction, the area under the receiver characteristic curve of 0.93 for oxacillin susceptibility prediction, and the area under the receiver characteristic curve of 0.89 for clindamycin susceptibility prediction. The generated multi-label prediction model provides serial antibiotic resistance, such as the susceptibilities of oxacillin and clindamycin in this study, for S. aureus-infected patients based on MALDI-TOF, which will provide guidance in antibiotic usage during the treatment taking the advantage of speed and efficiency.

Large-Scale Samples Based Rapid Detection of Ciprofloxacin Resistance in Klebsiella pneumoniae Using Machine Learning Methods.

Klebsiella pneumoniae is one of the most common causes of hospital- and community-acquired pneumoniae. Resistance to the extensively used quinolone antibiotic, such as ciprofloxacin, has increased in Klebsiella pneumoniae, which leads to the increase in the risk of initial antibiotic selection for Klebsiella pneumoniae treatment. Rapid and precise identification of ciprofloxacin-resistant Klebsiella pneumoniae (CIRKP) is essential for clinical therapy. Nowadays, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is another approach to discover antibiotic-resistant bacteria due to its shorter inspection time and lower cost than other current methods. Machine learning methods are introduced to assist in discovering significant biomarkers from MALDI-TOF MS data and construct prediction models for rapid antibiotic resistance identification. This study examined 16,997 samples taken from June 2013 to February 2018 as part of a longitudinal investigation done by Change Gung Memorial Hospitals (CGMH) at the Linkou branch. We applied traditional statistical approaches to identify significant biomarkers, and then a comparison was made between high-importance features in machine learning models and statistically selected features. Large-scale data guaranteed the statistical power of selected biomarkers. Besides, clustering analysis analyzed suspicious sub-strains to provide potential information about their influences on antibiotic resistance identification performance. For modeling, to simulate the real antibiotic resistance predicting challenges, we included basic information about patients and the types of specimen carriers into the model construction process and separated the training and testing sets by time. Final performance reached an area under the receiver operating characteristic curve (AUC) of 0.89 for support vector machine (SVM) and extreme gradient boosting (XGB) models. Also, logistic regression and random forest models both achieved AUC around 0.85. In conclusion, models provide sensitive forecasts of CIRKP, which may aid in early antibiotic selection against Klebsiella pneumoniae. The suspicious sub-strains could affect the model performance. Further works could keep on searching for methods to improve both the model accuracy and stability.

dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data.

The last 18 months, or more, have seen a profound shift in our global experience, with many of us navigating a once-in-100-year pandemic. To date, COVID-19 remains a life-threatening pandemic with little to no targeted therapeutic recourse. The discovery of novel antiviral agents, such as vaccines and drugs, can provide therapeutic solutions to save human beings from severe infections; however, there is no specifically effective antiviral treatment confirmed for now. Thus, great attention has been paid to the use of natural or artificial antimicrobial peptides (AMPs) as these compounds are widely regarded as promising solutions for the treatment of harmful microorganisms. Given the biological significance of AMPs, it was obvious that there was a significant need for a single platform for identifying and engaging with AMP data. This led to the creation of the dbAMP platform that provides comprehensive information about AMPs and facilitates their investigation and analysis. To date, the dbAMP has accumulated 26 447 AMPs and 2262 antimicrobial proteins from 3044 organisms using both database integration and manual curation of >4579 articles. In addition, dbAMP facilitates the evaluation of AMP structures using I-TASSER for automated protein structure prediction and structure-based functional annotation, providing predictive structure information for clinical drug development. Next-generation sequencing (NGS) and third-generation sequencing have been applied to generate large-scale sequencing reads from various environments, enabling greatly improved analysis of genome structure. In this update, we launch an efficient online tool that can effectively identify AMPs from genome/metagenome and proteome data of all species in a short period. In conclusion, these improvements promote the dbAMP as one of the most abundant and comprehensively annotated resources for AMPs. The updated dbAMP is now freely accessible at http://awi.cuhk.edu.cn/dbAMP.

MDRSA: A Web Based-Tool for Rapid Identification of Multidrug Resistant Staphylococcus aureus Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

As antibiotics resistance on superbugs has risen, more and more studies have focused on developing rapid antibiotics susceptibility tests (AST). Meanwhile, identification of multiple antibiotics resistance on Staphylococcus aureus provides instant information which can assist clinicians in administrating the appropriate prescriptions. In recent years, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful tool in clinical microbiology laboratories for the rapid identification of bacterial species. Yet, lack of study devoted on providing efficient methods to deal with the MS shifting problem, not to mention to providing tools incorporating the MALDI-TOF MS for the clinical use which deliver the instant administration of antibiotics to the clinicians. In this study, we developed a web tool, MDRSA, for the rapid identification of oxacillin-, clindamycin-, and erythromycin-resistant Staphylococcus aureus. Specifically, the kernel density estimation (KDE) was adopted to deal with the peak shifting problem, which is critical to analyze mass spectra data, and machine learning methods, including decision trees, random forests, and support vector machines, which were used to construct the classifiers to identify the antibiotic resistance. The areas under the receiver operating the characteristic curve attained 0.8 on the internal (10-fold cross validation) and external (independent testing) validation. The promising results can provide more confidence to apply these prediction models in the real world. Briefly, this study provides a web-based tool to provide rapid predictions for the resistance of antibiotics on Staphylococcus aureus based on the MALDI-TOF MS data. The web tool is available at: http://fdblab.csie.ncu.edu.tw/mdrsa/.

Clinically Applicable System for Rapidly Predicting Enterococcus faecium Susceptibility to Vancomycin.

Enterococcus faecium is a clinically important pathogen that can cause significant morbidity and death. In this study, we aimed to develop a machine learning (ML) algorithm-based rapid susceptibility method to distinguish vancomycin-resistant E. faecium (VREfm) and vancomycin-susceptible E. faecium (VSEfm) strains. A predictive model was developed and validated to distinguish VREfm and VSEfm strains by analyzing the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) spectra of unique E. faecium isolates from different specimen types. The algorithm used 5,717 mass spectra, including 2,795 VREfm and 2,922 VSEfm mass spectra, and was externally validated with 2,280 mass spectra of isolates (1,222 VREfm and 1,058 VSEfm strains). A random forest-based algorithm demonstrated overall good classification performances for the isolates from the specimens, with mean accuracy, sensitivity, and specificity of 0.78, 0.79, and 0.77, respectively, with 10-fold cross-validation, timewise validation, and external validation. Furthermore, the algorithm provided rapid results, which would allow susceptibility prediction prior to the availability of phenotypic susceptibility results. In conclusion, an ML algorithm designed using mass spectra obtained from the routine workflow may be able to rapidly differentiate VREfm strains from VSEfm strains; however, susceptibility results must be confirmed by routine methods, given the demonstrated performance of the assay. IMPORTANCE A modified binning method was incorporated to cluster MS shifting ions into a set of representative peaks based on a large-scale MS data set of clinical VREfm and VSEfm isolates, including 2,795 VREfm and 2,922 VSEfm isolates. Predictions with the algorithm were significantly more accurate than empirical antibiotic use, the accuracy of which was 0.50, based on the local epidemiology. The algorithm improved the accuracy of antibiotic administration, compared to empirical antibiotic prescription. An ML algorithm designed using MALDI-TOF MS spectra obtained from the routine workflow accurately differentiated VREfm strains from VSEfm strains, especially in blood and sterile body fluid samples, and can be applied to facilitate the rapid and accurate clinical testing of pathogens.

A large-scale investigation and identification of methicillin-resistant Staphylococcus aureus based on peaks binning of matrix-assisted laser desorption ionization-time of flight MS spectra.

Recent studies have demonstrated that the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) could be used to detect superbugs, such as methicillin-resistant Staphylococcus aureus (MRSA). Due to an increasingly clinical need to classify between MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) efficiently and effectively, we were motivated to develop a systematic pipeline based on a large-scale dataset of MS spectra. However, the shifting problem of peaks in MS spectra induced a low effectiveness in the classification between MRSA and MSSA isolates. Unlike previous works emphasizing on specific peaks, this study employs a binning method to cluster MS shifting ions into several representative peaks. A variety of bin sizes were evaluated to coalesce drifted or shifted MS peaks to a well-defined structured data. Then, various machine learning methods were performed to carry out the classification between MRSA and MSSA samples. Totally 4858 MS spectra of unique S. aureus isolates, including 2500 MRSA and 2358 MSSA instances, were collected by Chang Gung Memorial Hospitals, at Linkou and Kaohsiung branches, Taiwan. Based on the evaluation of Pearson correlation coefficients and the strategy of forward feature selection, a total of 200 peaks (with the bin size of 10 Da) were identified as the marker attributes for the construction of predictive models. These selected peaks, such as bins 2410-2419, 2450-2459 and 6590-6599 Da, have indicated remarkable differences between MRSA and MSSA, which were effective in the prediction of MRSA. The independent testing has revealed that the random forest model can provide a promising prediction with the area under the receiver operating characteristic curve (AUC) at 0.8450. When comparing to previous works conducted with hundreds of MS spectra, the proposed scheme demonstrates that incorporating machine learning method with a large-scale dataset of clinical MS spectra may be a feasible means for clinical physicians on the administration of correct antibiotics in shorter turn-around-time, which could reduce mortality, avoid drug resistance and shorten length of stay in hospital in the future.

Large-scale mass spectrometry data combined with demographics analysis rapidly predicts methicillin resistance in Staphylococcus aureus.

BACKGROUND: A mass spectrometry-based assessment of methicillin resistance in Staphylococcus aureus would have huge potential in addressing fast and effective prediction of antibiotic resistance. Since delays in the traditional antibiotic susceptibility testing, methicillin-resistant S. aureus remains a serious threat to human health. RESULTS: Here, linking a 7 years of longitudinal study from two cohorts in the Taiwan area of over 20 000 individually resolved methicillin susceptibility testing results, we identify associations of methicillin resistance with the demographics and mass spectrometry data. When combined together, these connections allow for machine-learning-based predictions of methicillin resistance, with an area under the receiver operating characteristic curve of >0.85 in both the discovery [95% confidence interval (CI) 0.88-0.90] and replication (95% CI 0.84-0.86) populations. CONCLUSIONS: Our predictive model facilitates early detection for methicillin resistance of patients with S. aureus infection. The large-scale antibiotic resistance study has unbiasedly highlighted putative candidates that could improve trials of treatment efficiency and inform on prescriptions.

Association of Fenofibrate and Diabetic Retinopathy in Type 2 Diabetic Patients: A Population-Based Retrospective Cohort Study in Taiwan.

Background and Objectives: Fenofibrate, a PPAR-α agonist, has been demonstrated to reduce the progression of diabetic retinopathy (DR) and the need for laser treatment in a FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study. However, in the subgroup of patients without pre-existing DR, there was no significant difference in the progression of DR between the fenofibrate group and the placebo group. In this study, we aim to investigate whether fenofibrate can decrease the risk of incident DR in a population-based cohort study of type 2 diabetic patients in Taiwan. Materials and Methods: A total of 32,253 type 2 diabetic patients without previous retinopathy were retrieved from 892,419 patients in 2001-2002. They were then divided into two groups based on whether they were exposed to fenofibrate or not. The patients were followed until a diagnosis of diabetic retinopathy was made or until the year 2008. Results: With a follow-up period of 6.8 ± 1.5 years and 5.4 ± 2.6 years for 2500 fenofibrate users and 29,753 non-users, respectively, the Cox proportional hazard regression analysis revealed that the hazard ratio (HR) of new onset retinopathy was 0.57 (95% CI 0.57-0.62, p < 0.001). After adjusting for hypertension; the Charlson comorbidity index (CCI); and medications such as angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), anticoagulants, gemfibrozil, statins, and hypoglycemic agents, the adjusted HR was 0.75 (95% CI 0.68-0.82, p < 0.001). The need for laser treatment has an HR and adjusted HR of 0.59 (95% CI 0.49-0.71, p < 0.001) and 0.67 (95% CI 0.56-0.81, p < 0.001), respectively. Conclusion: Our study showed that the long-term and regular use of fenofibrate may decrease the risk of incident retinopathy and the need for laser treatment in type 2 diabetic patients. Since there are limitations associated with our study, further investigations are necessary to confirm such an association.

Incorporating hybrid models into lysine malonylation sites prediction on mammalian and plant proteins.

Protein malonylation, a reversible post-translational modification of lysine residues, is associated with various biological functions, such as cellular regulation and pathogenesis. In proteomics, to improve our understanding of the mechanisms of malonylation at the molecular level, the identification of malonylation sites via an efficient methodology is essential. However, experimental identification of malonylated substrates via mass spectrometry is time-consuming, labor-intensive, and expensive. Although numerous methods have been developed to predict malonylation sites in mammalian proteins, the computational resource for identifying plant malonylation sites is very limited. In this study, a hybrid model incorporating multiple convolutional neural networks (CNNs) with physicochemical properties, evolutionary information, and sequenced-based features was developed for identifying protein malonylation sites in mammals. For plant malonylation, multiple CNNs and random forests were integrated into a secondary modeling phase using a support vector machine. The independent testing has demonstrated that the mammalian and plant malonylation models can yield the area under the receiver operating characteristic curves (AUC) at 0.943 and 0.772, respectively. The proposed scheme has been implemented as a web-based tool, Kmalo (https://fdblab.csie.ncu.edu.tw/kmalo/home.html), which can help facilitate the functional investigation of protein malonylation on mammals and plants.

Characterization and Identification of Natural Antimicrobial Peptides on Different Organisms.

Because of the rapid development of multidrug resistance, conventional antibiotics cannot kill pathogenic bacteria efficiently. New antibiotic treatments such as antimicrobial peptides (AMPs) can provide a possible solution to the antibiotic-resistance crisis. However, the identification of AMPs using experimental methods is expensive and time-consuming. Meanwhile, few studies use amino acid compositions (AACs) and physicochemical properties with different sequence lengths against different organisms to predict AMPs. Therefore, the major purpose of this study is to identify AMPs on seven categories of organisms, including amphibians, humans, fish, insects, plants, bacteria, and mammals. According to the one-rule attribute evaluation, the selected features were used to construct the predictive models based on the random forest algorithm. Compared to the accuracies of iAMP-2L (a web-server for identifying AMPs and their functional types), ADAM (a database of AMP), and MLAMP (a multi-label AMP classifier), the proposed method yielded higher than 92% in predicting AMPs on each category. Additionally, the sensitivities of the proposed models in the prediction of AMPs of seven organisms were higher than that of all other tools. Furthermore, several physicochemical properties (charge, hydrophobicity, polarity, polarizability, secondary structure, normalized van der Waals volume, and solvent accessibility) of AMPs were investigated according to their sequence lengths. As a result, the proposed method is a practical means to complement the existing tools in the characterization and identification of AMPs in different organisms.

Rapid classification of group B Streptococcus serotypes based on matrix-assisted laser desorption ionization-time of flight mass spectrometry and machine learning techniques.

BACKGROUND: Group B streptococcus (GBS) is an important pathogen that is responsible for invasive infections, including sepsis and meningitis. GBS serotyping is an essential means for the investigation of possible infection outbreaks and can identify possible sources of infection. Although it is possible to determine GBS serotypes by either immuno-serotyping or geno-serotyping, both traditional methods are time-consuming and labor-intensive. In recent years, the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported as an effective tool for the determination of GBS serotypes in a more rapid and accurate manner. Thus, this work aims to investigate GBS serotypes by incorporating machine learning techniques with MALDI-TOF MS to carry out the identification. RESULTS: In this study, a total of 787 GBS isolates, obtained from three research and teaching hospitals, were analyzed by MALDI-TOF MS, and the serotype of the GBS was determined by a geno-serotyping experiment. The peaks of mass-to-charge ratios were regarded as the attributes to characterize the various serotypes of GBS. Machine learning algorithms, such as support vector machine (SVM) and random forest (RF), were then used to construct predictive models for the five different serotypes (Types Ia, Ib, III, V, and VI). After optimization of feature selection and model generation based on training datasets, the accuracies of the selected models attained 54.9-87.1% for various serotypes based on independent testing data. Specifically, for the major serotypes, namely type III and type VI, the accuracies were 73.9 and 70.4%, respectively. CONCLUSION: The proposed models have been adopted to implement a web-based tool (GBSTyper), which is now freely accessible at http://csb.cse.yzu.edu.tw/GBSTyper/, for providing efficient and effective detection of GBS serotypes based on a MALDI-TOF MS spectrum. Overall, this work has demonstrated that the combination of MALDI-TOF MS and machine intelligence could provide a practical means of clinical pathogen testing.

Using a Large Margin Context-Aware Convolutional Neural Network to Automatically Extract Disease-Disease Association from Literature: Comparative Analytic Study.

BACKGROUND: Research on disease-disease association (DDA), like comorbidity and complication, provides important insights into disease treatment and drug discovery, and a large body of the literature has been published in the field. However, using current search tools, it is not easy for researchers to retrieve information on the latest DDA findings. First, comorbidity and complication keywords pull up large numbers of PubMed studies. Second, disease is not highlighted in search results. Finally, DDA is not identified, as currently no disease-disease association extraction (DDAE) dataset or tools are available. OBJECTIVE: As there are no available DDAE datasets or tools, this study aimed to develop (1) a DDAE dataset and (2) a neural network model for extracting DDA from the literature. METHODS: In this study, we formulated DDAE as a supervised machine learning classification problem. To develop the system, we first built a DDAE dataset. We then employed two machine learning models, support vector machine and convolutional neural network, to extract DDA. Furthermore, we evaluated the effect of using the output layer as features of the support vector machine-based model. Finally, we implemented large margin context-aware convolutional neural network architecture to integrate context features and convolutional neural networks through the large margin function. RESULTS: Our DDAE dataset consisted of 521 PubMed abstracts. Experiment results showed that the support vector machine-based approach achieved an F1 measure of 80.32%, which is higher than the convolutional neural network-based approach (73.32%). Using the output layer of convolutional neural network as a feature for the support vector machine does not further improve the performance of support vector machine. However, our large margin context-aware-convolutional neural network achieved the highest F1 measure of 84.18% and demonstrated that combining the hinge loss function of support vector machine with a convolutional neural network into a single neural network architecture outperforms other approaches. CONCLUSIONS: To facilitate the development of text-mining research for DDAE, we developed the first publicly available DDAE dataset consisting of disease mentions, Medical Subject Heading IDs, and relation annotations. We developed different conventional machine learning models and neural network architectures and evaluated their effects on our DDAE dataset. To further improve DDAE performance, we propose an large margin context-aware-convolutional neural network model for DDAE that outperforms other approaches.

Incorporating Statistical Test and Machine Intelligence Into Strain Typing of Staphylococcus haemolyticus Based on Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Staphylococcus haemolyticus is one of the most significant coagulase-negative staphylococci, and it often causes severe infections. Rapid strain typing of pathogenic S. haemolyticus is indispensable in modern public health infectious disease control, facilitating the identification of the origin of infections to prevent further infectious outbreak. Rapid identification enables the effective control of pathogenic infections, which is tremendously beneficial to critically ill patients. However, the existing strain typing methods, such as multi-locus sequencing, are of relatively high cost and comparatively time-consuming. A practical method for the rapid strain typing of pathogens, suitable for routine use in clinics and hospitals, is still not available. Matrix-assisted laser desorption ionization-time of flight mass spectrometry combined with machine learning approaches is a promising method to carry out rapid strain typing. In this study, we developed a statistical test-based method to determine the reference spectrum when dealing with alignment of mass spectra datasets, and constructed machine learning-based classifiers for categorizing different strains of S. haemolyticus. The area under the receiver operating characteristic curve and accuracy of multi-class predictions were 0.848 and 0.866, respectively. Additionally, we employed a variety of statistical tests and feature-selection strategies to identify the discriminative peaks that can substantially contribute to strain typing. This study not only incorporates statistical test-based methods to manage the alignment of mass spectra datasets but also provides a practical means to accomplish rapid strain typing of S. haemolyticus.

Characterization and identification of antimicrobial peptides with different functional activities.

In recent years, antimicrobial peptides (AMPs) have become an emerging area of focus when developing therapeutics hot spot residues of proteins are dominant against infections. Importantly, AMPs are produced by virtually all known living organisms and are able to target a wide range of pathogenic microorganisms, including viruses, parasites, bacteria and fungi. Although several studies have proposed different machine learning methods to predict peptides as being AMPs, most do not consider the diversity of AMP activities. On this basis, we specifically investigated the sequence features of AMPs with a range of functional activities, including anti-parasitic, anti-viral, anti-cancer and anti-fungal activities and those that target mammals, Gram-positive and Gram-negative bacteria. A new scheme is proposed to systematically characterize and identify AMPs and their functional activities. The 1st stage of the proposed approach is to identify the AMPs, while the 2nd involves further characterization of their functional activities. Sequential forward selection was employed to extract potentially informative features that are possibly associated with the functional activities of the AMPs. These features include hydrophobicity, the normalized van der Waals volume, polarity, charge and solvent accessibility-all of which are essential attributes in classifying between AMPs and non-AMPs. The results revealed the 1st stage AMP classifier was able to achieve an area under the receiver operating characteristic curve (AUC) value of 0.9894. During the 2nd stage, we found pseudo amino acid composition to be an informative attribute when differentiating between AMPs in terms of their functional activities. The independent testing results demonstrated that the AUCs of the multi-class models were 0.7773, 0.9404, 0.8231, 0.8578, 0.8648, 0.8745 and 0.8672 for anti-parasitic, anti-viral, anti-cancer, anti-fungal AMPs and those that target mammals, Gram-positive and Gram-negative bacteria, respectively. The proposed scheme helps facilitate biological experiments related to the functional analysis of AMPs. Additionally, it was implemented as a user-friendly web server (AMPfun, http://fdblab.csie.ncu.edu.tw/AMPfun/index.html) that allows individuals to explore the antimicrobial functions of peptides of interest.