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Determining the catalytic residues in an enzyme is critical to our understanding the relationship between protein sequence, structure, function, and enhancing our ability to design novel enzymes and their inhibitors. Although many enzymes have been sequenced, and their primary and tertiary structures determined, experimental methods for enzyme functional characterization lag behind. Because experimental methods used for identifying catalytic residues are resource- and labor-intensive, computational approaches have considerable value and are highly desirable for their ability to complement experimental studies in identifying catalytic residues and helping to bridge the sequence-structure-function gap. In this study, we describe a new computational method called PREvaIL for predicting enzyme catalytic residues. This method was developed by leveraging a comprehensive set of informative features extracted from multiple levels, including sequence, structure, and residue-contact network, in a random forest machine-learning framework. Extensive benchmarking experiments on eight different datasets based on 10-fold cross-validation and independent tests, as well as side-by-side performance comparisons with seven modern sequence- and structure-based methods, showed that PREvaIL achieved competitive predictive performance, with an area under the receiver operating characteristic curve and area under the precision-recall curve ranging from 0.896 to 0.973 and from 0.294 to 0.523, respectively. We demonstrated that this method was able to capture useful signals arising from different levels, leveraging such differential but useful types of features and allowing us to significantly improve the performance of catalytic residue prediction. We believe that this new method can be utilized as a valuable tool for both understanding the complex sequence-structure-function relationships of proteins and facilitating the characterization of novel enzymes lacking functional annotations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose Post-injury health service utilization (HSU) contributes to injury outcomes, but limited studies investigated their relationship. This study aims to group injured patients in transport accidents based on minimal historical information of their HSU so that the groups are meaningfully associated with the outcome of interest. Methods The data include 20,692 injured patients who had compensation claims over 3 years. We propose a hybrid approach, combining unsupervised and supervised machine learning methods. Based on the first week post-injury data, we identify a proper clustering of patients best associated with total cost to recovery, as well as the discovery of HSU patterns. This allows developing models to accurately predict the outcome of interest using the discovered patterns. Furthermore, we propose to use decision tree classifiers to accurately classify future patients into the discovered clusters using their first week post-injury information. Results Our hybrid approach has identified eight patient groups. The compactness of the resulted clusters, assessed by Average Silhouette Width metric, is 0.71 indicating well-defined clusters. The resulted patient groups are highly predictive of injury outcomes. They improve the cost predictability more than twice in comparison with predictors such as gender, age and injury type. These groups also have substantial association with patients' recovery. The transparency and interpretability of decision trees allow integrating the resulting classification rules conveniently in operational processes. Conclusions This study provides a framework to discover knowledge and useful insights for health service providers and policy makers to control injury outcomes, and consequently to reduce the severity of transport accidents. [ABSTRACT FROM AUTHOR]

The roles of proteolytic cleavage have been intensively investigated and discussed during the past two decades. This irreversible chemical process has been frequently reported to influence a number of crucial biological processes (BPs), such as cell cycle, protein regulation and inflammation. A number of advanced studies have been published aiming at deciphering the mechanisms of proteolytic cleavage. Given its significance and the large number of functionally enriched substrates targeted by specific proteases, many computational approaches have been established for accurate prediction of protease-specific substrates and their cleavage sites. Consequently, there is an urgent need to systematically assess the state-of-the-art computational approaches for protease-specific cleavage site prediction to further advance the existing methodologies and to improve the prediction performance. With this goal in mind, in this article, we carefully evaluated a total of 19 computational methods (including 8 scoring function-based methods and 11 machine learning-based methods) in terms of their underlying algorithm, calculated features, performance evaluation and software usability. Then, extensive independent tests were performed to assess the robustness and scalability of the reviewed methods using our carefully prepared independent test data sets with 3641 cleavage sites (specific to 10 proteases). The comparative experimental results demonstrate that PROSPERous is the most accurate generic method for predicting eight protease-specific cleavage sites, while GPS-CCD and LabCaS outperformed other predictors for calpain-specific cleavage sites. Based on our review, we then outlined some potential ways to improve the prediction performance and ease the computational burden by applying ensemble learning, deep learning, positive unlabeled learning and parallel and distributed computing techniques. We anticipate that our study will serve as a practical and useful guide for interested readers to further advance next-generation bioinformatics tools for protease-specific cleavage site prediction. [ABSTRACT FROM AUTHOR]

Statistical machine translation systems are usually trained on large amounts of bilingual text (used to learn a translation model), and also large amounts of monolingual text in the target language (used to train a language model). In this article we explore the use of semi-supervised model adaptation methods for the effective use of monolingual data from the source language in order to improve translation quality. We propose several algorithms with this aim, and present the strengths and weaknesses of each one. We present detailed experimental evaluations on the French—English EuroParl data set and on data from the NIST Chinese—English large-data track. We show a significant improvement in translation quality on both tasks. [ABSTRACT FROM AUTHOR]

Clinical audit of invasive mold disease (IMD) in hematology patients is inefficient due to the difficulties of case finding. This results in antifungal stewardship (AFS) programs preferentially reporting drug cost and consumption rather than measures that actually reflect quality of care. We used machine learning-based natural language processing (NLP) to non-selectively screen chest tomography (CT) reports for pulmonary IMD, verified by clinical review against international definitions and benchmarked against key AFS measures. NLP screened 3014 reports from 1 September 2008 to 31 December 2017, generating 784 positives that after review, identified 205 IMD episodes (44% probable-proven) in 185 patients from 50,303 admissions. Breakthrough-probable/proven-IMD on antifungal prophylaxis accounted for 60% of episodes with serum monitoring of voriconazole or posaconazole in the 2 weeks prior performed in only 53% and 69% of episodes, respectively. Fiberoptic bronchoscopy within 2 days of CT scan occurred in only 54% of episodes. The average turnaround of send-away bronchoalveolar galactomannan of 12 days (range 7–22) was associated with high empiric liposomal amphotericin consumption. A random audit of 10% negative reports revealed two clinically significant misses (0.9%, 2/223). This is the first successful use of applied machine learning for institutional IMD surveillance across an entire hematology population describing process and outcome measures relevant to AFS. Compared to current methods of clinical audit, semi-automated surveillance using NLP is more efficient and inclusive by avoiding restrictions based on any underlying hematologic condition, and has the added advantage of being potentially scalable. [ABSTRACT FROM AUTHOR]

It has been shown that minimum free-energy structure for RNAs and RNA-RNA interaction is often incorrect due to inaccuracies in the energy parameters and inherent limitations of the energy model. In contrast, ensemble-based quantities such as melting temperature and equilibrium concentrations can be more reliably predicted. Even structure prediction by sampling from the ensemble and clustering those structures by Sfold has proven to be more reliable than minimum free energy structure prediction. The main obstacle for ensemble-based approaches is the computational complexity of the partition function and base-pairing probabilities. For instance, the space complexity of the partition function for RNA-RNA interaction is O( n4) and the time complexity is O( n6), which is prohibitively large. Our goal in this article is to present a fast algorithm, based on sparse folding, to calculate an upper bound on the partition function. Our work is based on the recent algorithm of Hazan and Jaakkola (). The space complexity of our algorithm is the same as that of sparse folding algorithms, and the time complexity of our algorithm is O( MFE( n)ℓ) for single RNA and O( MFE( m, n)ℓ) for RNA-RNA interaction in practice, in which MFE is the running time of sparse folding and ℓ ≤ n (ℓ ≤ n + m) is a sequence-dependent parameter. [ABSTRACT FROM AUTHOR]