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Event extraction is an important, but challenging task. Many existing techniques decompose it into event and argument detection/classification subtasks, which are complex structured prediction problems. Generation-based extraction techniques lessen the complexity of the problem formulation and are able to leverage the reasoning capabilities of large pretrained language models. However, they still suffer from poor zero-shot generalizability and are ineffective in handling long contexts such as documents. We propose a generative event extraction model, KC-GEE, that addresses these limitations. A key contribution of KC-GEE is a novel knowledge-based conditioning technique that injects the schema of candidate event types as the prefix into each layer of an encoder-decoder language model. This enables effective zero-shot learning and improves supervised learning. Our experiments on two benchmark datasets demonstrate the strong performance of our KC-GEE model. It achieves particularly strong results in the challenging document-level extraction task and in the zero-shot learning setting, outperforming state-of-the-art models by up to 5.4 absolute F1 points. [ABSTRACT FROM AUTHOR]

Machine translation (MT) is an important task in natural language processing (NLP), as it automates the translation process and reduces the reliance on human translators. With the resurgence of neural networks, the translation quality surpasses that of the translations obtained using statistical techniques for most languagepairs. Up until a few years ago, almost all of the neural translation models translated sentences independently, without incorporating the wider document-context and inter-dependencies among the sentences. The aim of this survey article is to highlight the major works that have been undertaken in the space of document-level machine translation after the neural revolution, so researchers can recognize the current state and future directions of this field. We provide an organization of the literature based on novelties in modelling and architectures as well as training and decoding strategies. In addition, we cover evaluation strategies that have been introduced to account for the improvements in document MT, including automatic metrics and discourse-targeted test sets. We conclude by presenting possible avenues for future exploration in this research field. [ABSTRACT FROM AUTHOR]

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]

Conventional general-purpose distance-based similarity measures, such as Minkowski distance (also known as ℓ p -norm with p > 0 ), are data-independent and sensitive to units or scales of measurement. There are existing general-purpose data-dependent measures, such as rank difference, Lin's probabilistic measure and m p -dissimilarity ( p > 0 ), which are not sensitive to units or scales of measurement. Although they have been shown to be more effective than the traditional distance measures, their characteristics and relative performances have not been investigated. In this paper, we study the characteristics and relationships of different general-purpose data-dependent measures. We generalise m p -dissimilarity where p ≥ 0 by introducing m 0 -dissimilarity and show that it is a generic data-dependent measure with data-dependent self-similarity, of which rank difference and Lin's measure are special cases with data-independent self-similarity. We evaluate the effectiveness of a wide range of general-purpose data-dependent and data-independent measures in the content-based information retrieval and kNN classification tasks. Our findings show that the fully data-dependent measure of m p -dissimilarity is a more effective alternative to other data-dependent and commonly-used distance-based similarity measures as its task-specific performance is more consistent across a wide range of datasets. [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]

Identifying those patient groups, who have unwanted outcomes, in the early stages is crucial to providing the most appropriate level of care. In this study, we intend to find distinctive patterns in health service use (HSU) of transport accident injured patients within the first week post-injury. Aiming those patterns that are associated with the outcome of interest. To recognize these patterns, we propose a multi-objective optimization model that minimizes the k-medians cost function and regression error simultaneously. Thus, we use a semi-supervised clustering approach to identify patient groups based on HSU patterns and their association with total cost. To solve the optimization problem, we introduce an evolutionary algorithm using stochastic gradient descent and Pareto optimal solutions. As a result, we find the best optimal clusters by minimizing both objective functions. The results show that the proposed semi-supervised approach identifies distinct groups of HSUs and contributes to predict total cost. Also, the experiments prove the performance of the multi-objective approach in comparison with singleobjective approaches. [ABSTRACT FROM AUTHOR]

Proteases are enzymes that specifically cleave the peptide backbone of their target proteins. As an important type of irreversible post-translational modification, protein cleavage underlies many key physiological processes. When dysregulated, proteases' actions are associated with numerous diseases. Many proteases are highly specific, cleaving only those target substrates that present certain particular amino acid sequence patterns. Therefore, tools that successfully identify potential target substrates for proteases may also identify previously unknown, physiologically relevant cleavage sites, thus providing insights into biological processes and guiding hypothesis-driven experiments aimed at verifying protease-substrate interaction. In this work, we present PROSPERous, a tool for rapid in silico prediction of protease-specific cleavage sites in substrate sequences. Our tool is based on logistic regression models and uses different scoring functions and their pairwise combinations to subsequently predict potential cleavage sites. PROSPERous represents a state-of-the-art tool that enables fast, accurate and high-throughput prediction of substrate cleavage sites for 90 proteases. [ABSTRACT FROM AUTHOR]

Nearest neighbor search is a core process in many data mining algorithms. Finding reliable closest matches of a test instance is still a challenging task as the effectiveness of many general-purpose distance measures such as $$\ell _p$$ -norm decreases as the number of dimensions increases. Their performances vary significantly in different data distributions. This is mainly because they compute the distance between two instances solely based on their geometric positions in the feature space, and data distribution has no influence on the distance measure. This paper presents a simple data-dependent general-purpose dissimilarity measure called ' $$m_p$$ -dissimilarity'. Rather than relying on geometric distance, it measures the dissimilarity between two instances as a probability mass in a region that encloses the two instances in every dimension. It deems two instances in a sparse region to be more similar than two instances of equal inter-point geometric distance in a dense region. Our empirical results in k-NN classification and content-based multimedia information retrieval tasks show that the proposed $$m_p$$ -dissimilarity measure produces better task-specific performance than existing widely used general-purpose distance measures such as $$\ell _p$$ -norm and cosine distance across a wide range of moderate- to high-dimensional data sets with continuous only, discrete only, and mixed attributes. [ABSTRACT FROM AUTHOR]

Data depth is a statistical method which models data distribution in terms of center-outward ranking rather than density or linear ranking. While there are a lot of academic interests, its applications are hampered by the lack of a method which is both robust and efficient. This paper introduces Half-Space Mass which is a significantly improved version of half-space data depth. Half-Space Mass is the only data depth method which is both robust and efficient, as far as we know. We also reveal four theoretical properties of Half-Space Mass: (i) its resultant mass distribution is concave regardless of the underlying density distribution, (ii) its maximum point is unique which can be considered as median, (iii) the median is maximally robust, and (iv) its estimation extends to a higher dimensional space in which the convex hull of the dataset occupies zero volume. We demonstrate the power of Half-Space Mass through its applications in two tasks. In anomaly detection, being a maximally robust location estimator leads directly to a robust anomaly detector that yields a better detection accuracy than half-space depth; and it runs orders of magnitude faster than $$L_2$$ depth, an existing maximally robust location estimator. In clustering, the Half-Space Mass version of K-means overcomes three weaknesses of K-means. [ABSTRACT FROM AUTHOR]

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ?40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA-RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 'CNA-devoid' subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome. [ABSTRACT FROM AUTHOR]

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. [ABSTRACT FROM AUTHOR]

Motivation: The study of cancer genomes now routinely involves using next-generation sequencing technology (NGS) to profile tumours for single nucleotide variant (SNV) somatic mutations. However, surprisingly few published bioinformatics methods exist for the specific purpose of identifying somatic mutations from NGS data and existing tools are often inaccurate, yielding intolerably high false prediction rates. As such, the computational problem of accurately inferring somatic mutations from paired tumour/normal NGS data remains an unsolved challenge.Results: We present the comparison of four standard supervised machine learning algorithms for the purpose of somatic SNV prediction in tumour/normal NGS experiments. To evaluate these approaches (random forest, Bayesian additive regression tree, support vector machine and logistic regression), we constructed 106 features representing 3369 candidate somatic SNVs from 48 breast cancer genomes, originally predicted with naive methods and subsequently revalidated to establish ground truth labels. We trained the classifiers on this data (consisting of 1015 true somatic mutations and 2354 non-somatic mutation positions) and conducted a rigorous evaluation of these methods using a cross-validation framework and hold-out test NGS data from both exome capture and whole genome shotgun platforms. All learning algorithms employing predictive discriminative approaches with feature selection improved the predictive accuracy over standard approaches by statistically significant margins. In addition, using unsupervised clustering of the ground truth ‘false positive’ predictions, we noted several distinct classes and present evidence suggesting non-overlapping sources of technical artefacts illuminating important directions for future study.Availability: Software called MutationSeq and datasets are available from http://compbio.bccrc.ca.Contact: saparicio@bccrc.caSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

Mantle cell lymphoma (MCL) and small lymphocytic lymphoma (SLL) exhibit similar but distinct immunophenotypic profiles. Many cases can be diagnosed readily by flow cytometry (FCM) alone; however, ambiguous cases are frequently encountered and necessitate additional studies, including immunohistochemical staining for cyclin D1 and fluorescence in situ hybridization for IgH-CCND1 rearrangement. To determine if greater diagnostic accuracy could be achieved from FCM data alone, we developed an unbiased, machine-based algorithm to identify features that best distinguish between the 2 diseases. By applying conventional diagnostic criteria to the flow cytometry data, we were able to assign 28 of 44 (64%) MCL and 48 of 70 (69%) SLL cases correctly. In contrast, we were able to assign all 44 (100%) MCL and 68 of 70 (97%) SLL cases correctly using a novel set of criteria, as identified by our automated approach. The most discriminating feature was the CD20/CD23 mean fluorescence intensity ratio, and we found unexpectedly that inclusion of FMC7 expression in the diagnostic algorithm actually reduced its accuracy. This study demonstrates that computational methods can be used on existing clinical FCM data to improve diagnostic accuracy and suggests similar computational approaches could be used to identify novel prognostic markers and perhaps subdivide existing or define new diagnostic entities. [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]