Cancer registration is a vital source of information for government-driven cancer prevention and control policies. However, cancer registry abstraction is a complex and labor-intensive process, requiring the extraction of structured data from large volumes of unstructured clinical reports. To address these challenges, we propose a hierarchical temporal attention network leveraging attention mechanisms at the word, sentence, and document levels, while incorporating temporal and report type information to capture nuanced relationships within patients' longitudinal data. To ensure robust evaluation, a stratified sampling algorithm was developed to balance the training, validation, and test datasets across 23 coding tasks, mitigating potential biases. The proposed method achieved an average F1-score of 0.82, outperforming existing approaches by prioritizing task-relevant words, sentences, and reports through its attention mechanism. An ablation study confirmed the critical contributions of the proposed components. Furthermore, a prototype visualization tool was developed to present interpretability, providing cancer registrars with insights into the decision-making process by visualizing attention at multiple levels of granularity. Overall, the proposed methods combined with the interpretabilityfocused visualization tool, represent a significant step toward automating cancer registry abstraction from unstructured clinical text in longitudinal settings.

OBJECTIVE: An adverse drug event (ADE) refers to an injury resulting from medical intervention related to a drug including harm caused by drugs or from the usage of drugs. Extracting ADEs from clinical records can help physicians associate adverse events to targeted drugs. MATERIALS AND METHODS: We proposed a cascading architecture to recognize medical concepts including ADEs, drug names, and entities related to drugs. The architecture includes a preprocessing method and an ensemble of conditional random fields (CRFs) and neural network-based models to respectively address the challenges of surrogate string and overlapping annotation boundaries observed in the employed ADEs and medication extraction (ADME) corpus. The effectiveness of applying different pretrained and postprocessed word embeddings for the ADME task was also studied. RESULTS: The empirical results showed that both CRFs and neural network-based models provide promising solution for the ADME task. The neural network-based models particularly outperformed CRFs in concept types involving narrative descriptions. Our best run achieved an overall micro F-score of 0.919 on the employed corpus. Our results also suggested that the Global Vectors for word representation embedding in general domain provides a very strong baseline, which can be further improved by applying the principal component analysis to generate more isotropic vectors. CONCLUSIONS: We have demonstrated that the proposed cascading architecture can handle the problem of overlapped annotations and further improve the overall recall and F-scores because the architecture enables the developed models to exploit more context information and forms an ensemble for creating a stronger recognizer.

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 23 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. miRNAs have been considered as good candidates for early detection or prognosis biomarkers for various diseases. Validated miRNA targets are usually reported in literature, necessitating researchers to manually screen through the related literature to keep up-to-date with novel findings. However, the amount of miRNA-related literature is increasing rapidly which makes it difficult for researchers to keep up to date. This study develops a text mining pipeline based on the statistical principle-based approach (SPBA) to detect MiRNA-Target Interactions (MTIs) mentioned in literatures. SPBA uses a collection of principles to represent linguistic concepts or rules used by human for describing MTIs. Each principle is composed of a collection of slots, which can be automatically learned from training data by merging the labeled slot sequences into more representative principles through a dominating set algorithm. Followed by a partial matching algorithm, the proposed approach can successfully recognize miRNA mentions and extract their MTIs in articles with a promising F-score of 98.8% and an accuracy of 71.43%.

Electronic medical records (EMRs) for diabetic patients contain information about heart disease risk factors such as high blood pressure, cholesterol levels, and smoking status. Discovering the described risk factors and tracking their progression over time may support medical personnel in making clinical decisions, as well as facilitate data modeling and biomedical research. Such highly patient-specific knowledge is essential to driving the advancement of evidence-based practice, and can also help improve personalized medicine and care. One general approach for tracking the progression of diseases and their risk factors described in EMRs is to first recognize all temporal expressions, and then assign each of them to the nearest target medical concept. However, this method may not always provide the correct associations. In light of this, this work introduces a context-aware approach to assign the time attributes of the recognized risk factors by reconstructing contexts that contain more reliable temporal expressions. The evaluation results on the i2b2 test set demonstrate the efficacy of the proposed approach, which achieved an F-score of 0.897. To boost the approach's ability to process unstructured clinical text and to allow for the reproduction of the demonstrated results, a set of developed .NET libraries used to develop the system is available at https://sites.google.com/site/hongjiedai/projects/nttmuclinicalnet.

Coronary artery disease (CAD) often leads to myocardial infarction, which may be fatal. Risk factors can be used to predict CAD, which may subsequently lead to prevention or early intervention. Patient data such as co-morbidities, medication history, social history and family history are required to determine the risk factors for a disease. However, risk factor data are usually embedded in unstructured clinical narratives if the data is not collected specifically for risk assessment purposes. Clinical text mining can be used to extract data related to risk factors from unstructured clinical notes. This study presents methods to extract Framingham risk factors from unstructured electronic health records using clinical text mining and to calculate 10-year coronary artery disease risk scores in a cohort of diabetic patients. We developed a rule-based system to extract risk factors: age, gender, total cholesterol, HDL-C, blood pressure, diabetes history and smoking history. The results showed that the output from the text mining system was reliable, but there was a significant amount of missing data to calculate the Framingham risk score. A systematic approach for understanding missing data was followed by implementation of imputation strategies. An analysis of the 10-year Framingham risk scores for coronary artery disease in this cohort has shown that the majority of the diabetic patients are at moderate risk of CAD.

OBJECTIVE: Patient discharge summaries provide detailed medical information about hospitalized patients and are a rich resource of data for clinical record text mining. The textual expressions of this information are highly variable. In order to acquire a precise understanding of the patient, it is important to uncover the relationship between all instances in the text. In natural language processing (NLP), this task falls under the category of coreference resolution. DESIGN: A key contribution of this paper is the application of contextual-dependent rules that describe relationships between coreference pairs. To resolve phrases that refer to the same entity, the authors use these rules in three representative NLP systems: one rule-based, another based on the maximum entropy model, and the last a system built on the Markov logic network (MLN) model. RESULTS: The experimental results show that the proposed MLN-based system outperforms the baseline system (exact match) by average F-scores of 4.3% and 5.7% on the Beth and Partners datasets, respectively. Finally, the three systems were integrated into an ensemble system, further improving performance to 87.21%, which is 4.5% more than the official i2b2 Track 1C average (82.7%). CONCLUSION: In this paper, the main challenges in the resolution of coreference relations in patient discharge summaries are described. Several rules are proposed to exploit contextual information, and three approaches presented. While single systems provided promising results, an ensemble approach combining the three systems produced a better performance than even the best single system.

In this paper, we describe how we integrated an artificial intelligence (AI) system into the PubMed search website using augmented browsing technology. Our system dynamically enriches the PubMed search results displayed in a user's browser with semantic annotation provided by several natural language processing (NLP) subsystems, including a sentence splitter, a part-of-speech tagger, a named entity recognizer, a section categorizer and a gene normalizer (GN). After our system is installed, the PubMed search results page is modified on the fly to categorize sections and provide additional information on gene and gene products indentified by our NLP subsystems. In addition, GN involves three main steps: candidate ID matching, false positive filtering and disambiguation, which are highly dependent on each other. We propose a joint model using a Markov logic network (MLN) to model the dependencies found in GN. The experimental results show that our joint model outperforms a baseline system that executes the three steps separately. The developed system is available at https://sites.google.com/site/pubmedannotationtool 4ijcai/home.

MOTIVATION: Gene normalization (GN) is the task of normalizing a textual gene mention to a unique gene database ID. Traditional top performing GN systems usually need to consider several constraints to make decisions in the normalization process, including filtering out false positives, or disambiguating an ambiguous gene mention, to improve system performance. However, these constraints are usually executed in several separate stages and cannot use each other's input/output interactively. In this article, we propose a novel approach that employs a Markov logic network (MLN) to model the constraints used in the GN task. Firstly, we show how various constraints can be formulated and combined in an MLN. Secondly, we are the first to apply the two main concepts of co-reference resolution-discourse salience in centering theory and transitivity-to GN models. Furthermore, to make our results more relevant to developers of information extraction applications, we adopt the instance-based precision/recall/F-measure (PRF) in addition to the article-wide PRF to assess system performance. RESULTS: Experimental results show that our system outperforms baseline and state-of-the-art systems under two evaluation schemes. Through further analysis, we have found several unexplored challenges in the GN task. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: DNA methylation is regarded as a potential biomarker in the diagnosis and treatment of cancer. The relations between aberrant gene methylation and cancer development have been identified by a number of recent scientific studies. In a previous work, we used co-occurrences to mine those associations and compiled the MeInfoText 1.0 database. To reduce the amount of manual curation and improve the accuracy of relation extraction, we have now developed MeInfoText 2.0, which uses a machine learning-based approach to extract gene methylation-cancer relations. DESCRIPTION: Two maximum entropy models are trained to predict if aberrant gene methylation is related to any type of cancer mentioned in the literature. After evaluation based on 10-fold cross-validation, the average precision/recall rates of the two models are 94.7/90.1 and 91.8/90% respectively. MeInfoText 2.0 provides the gene methylation profiles of different types of human cancer. The extracted relations with maximum probability, evidence sentences, and specific gene information are also retrievable. The database is available at http://bws.iis.sinica.edu.tw:8081/MeInfoText2/. CONCLUSION: The previous version, MeInfoText, was developed by using association rules, whereas MeInfoText 2.0 is based on a new framework that combines machine learning, dictionary lookup and pattern matching for epigenetics information extraction. The results of experiments show that MeInfoText 2.0 outperforms existing tools in many respects. To the best of our knowledge, this is the first study that uses a hybrid approach to extract gene methylation-cancer relations. It is also the first attempt to develop a gene methylation and cancer relation corpus.

BACKGROUND: We report the Gene Normalization (GN) challenge in BioCreative III where participating teams were asked to return a ranked list of identifiers of the genes detected in full-text articles. For training, 32 fully and 500 partially annotated articles were prepared. A total of 507 articles were selected as the test set. Due to the high annotation cost, it was not feasible to obtain gold-standard human annotations for all test articles. Instead, we developed an Expectation Maximization (EM) algorithm approach for choosing a small number of test articles for manual annotation that were most capable of differentiating team performance. Moreover, the same algorithm was subsequently used for inferring ground truth based solely on team submissions. We report team performance on both gold standard and inferred ground truth using a newly proposed metric called Threshold Average Precision (TAP-k). RESULTS: We received a total of 37 runs from 14 different teams for the task. When evaluated using the gold-standard annotations of the 50 articles, the highest TAP-k scores were 0.3297 (k=5), 0.3538 (k=10), and 0.3535 (k=20), respectively. Higher TAP-k scores of 0.4916 (k=5, 10, 20) were observed when evaluated using the inferred ground truth over the full test set. When combining team results using machine learning, the best composite system achieved TAP-k scores of 0.3707 (k=5), 0.4311 (k=10), and 0.4477 (k=20) on the gold standard, representing improvements of 12.4%, 21.8%, and 26.6% over the best team results, respectively. CONCLUSIONS: By using full text and being species non-specific, the GN task in BioCreative III has moved closer to a real literature curation task than similar tasks in the past and presents additional challenges for the text mining community, as revealed in the overall team results. By evaluating teams using the gold standard, we show that the EM algorithm allows team submissions to be differentiated while keeping the manual annotation effort feasible. Using the inferred ground truth we show measures of comparative performance between teams. Finally, by comparing team rankings on gold standard vs. inferred ground truth, we further demonstrate that the inferred ground truth is as effective as the gold standard for detecting good team performance.

The interactor normalization task (INT) is to identify genes that play the interactor role in protein-protein interactions (PPIs), to map these genes to unique IDs, and to rank them according to their normalized confidence. INT has two subtasks: gene normalization (GN) and interactor ranking. The main difficulties of INT GN are identifying genes across species and using full papers instead of abstracts. To tackle these problems, we developed a multistage GN algorithm and a ranking method, which exploit information in different parts of a paper. Our system achieved a promising AUC of 0.43471. Using the multistage GN algorithm, we have been able to improve system performance (AUC) by 1.719 percent compared to a one-stage GN algorithm. Our experimental results also show that with full text, versus abstract only, INT AUC performance was 22.6 percent higher.

Abstract Summary: PubMed-EX is a browser extension that marks up PubMed search results with additional text-mining information. PubMed-EX's page mark-up, which includes section categorization and gene/disease and relation mark-up, can help researchers to quickly focus on key terms and provide additional information on them. All text processing is performed server-side, freeing up user resources. Availability: PubMed-EX is freely available at http://bws.iis.sinica.edu.tw/PubMed-EX and http://iisr.cse.yzu.edu.tw:8000/PubMed-EX/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

BACKGROUND: The genetic factors leading to hypertension have been extensively studied, and large numbers of research papers have been published on the subject. One of hypertension researchers' primary research tasks is to locate key hypertension-related genes in abstracts. However, gathering such information with existing tools is not easy: (1) Searching for articles often returns far too many hits to browse through. (2) The search results do not highlight the hypertension-related genes discovered in the abstract. (3) Even though some text mining services mark up gene names in the abstract, the key genes investigated in a paper are still not distinguished from other genes. To facilitate the information gathering process for hypertension researchers, one solution would be to extract the key hypertension-related genes in each abstract. Three major tasks are involved in the construction of this system: (1) gene and hypertension named entity recognition, (2) section categorization, and (3) gene-hypertension relation extraction. RESULTS: We first compare the retrieval performance achieved by individually adding template features and position features to the baseline system. Then, the combination of both is examined. We found that using position features can almost double the original AUC score (0.8140 vs.0.4936) of the baseline system. However, adding template features only results in marginal improvement (0.0197). Including both improves AUC to 0.8184, indicating that these two sets of features are complementary, and do not have overlapping effects. We then examine the performance in a different domain--diabetes, and the result shows a satisfactory AUC of 0.83. CONCLUSION: Our approach successfully exploits template features to recognize true hypertension-related gene mentions and position features to distinguish key genes from other related genes. Templates are automatically generated and checked by biologists to minimize labor costs. Our approach integrates the advantages of machine learning models and pattern matching. To the best of our knowledge, this the first systematic study of extracting hypertension-related genes and the first attempt to create a hypertension-gene relation corpus based on the GAD database. Furthermore, our paper proposes and tests novel features for extracting key hypertension genes, such as relative position, section, and template features, which could also be applied to key-gene extraction for other diseases.

BACKGROUND: Semantic role labeling (SRL) is an important text analysis technique. In SRL, sentences are represented by one or more predicate-argument structures (PAS). Each PAS is composed of a predicate (verb) and several arguments (noun phrases, adverbial phrases, etc.) with different semantic roles, including main arguments (agent or patient) as well as adjunct arguments (time, manner, or location). PropBank is the most widely used PAS corpus and annotation format in the newswire domain. In the biomedical field, however, more detailed and restrictive PAS annotation formats such as PASBio are popular. Unfortunately, due to the lack of an annotated PASBio corpus, no publicly available machine-learning (ML) based SRL systems based on PASBio have been developed. In previous work, we constructed a biomedical corpus based on the PropBank standard called BioProp, on which we developed an ML-based SRL system, BIOSMILE. In this paper, we aim to build a system to convert BIOSMILE's BioProp annotation output to PASBio annotation. Our system consists of BIOSMILE in combination with a BioProp-PASBio rule-based converter, and an additional semi-automatic rule generator. RESULTS: Our first experiment evaluated our rule-based converter's performance independently from BIOSMILE performance. The converter achieved an F-score of 85.29%. The second experiment evaluated combined system (BIOSMILE + rule-based converter). The system achieved an F-score of 69.08% for PASBio's 29 verbs. CONCLUSION: Our approach allows PAS conversion between BioProp and PASBio annotation using BIOSMILE alongside our newly developed semi-automatic rule generator and rule-based converter. Our system can match the performance of other state-of-the-art domain-specific ML-based SRL systems and can be easily customized for PASBio application development.

BACKGROUND: Experimentally verified protein-protein interactions (PPI) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be made faster by ranking newly-published articles' relevance to PPI, a task which we approach here by designing a machine-learning-based PPI classifier. All classifiers require labeled data, and the more labeled data available, the more reliable they become. Although many PPI databases with large numbers of labeled articles are available, incorporating these databases into the base training data may actually reduce classification performance since the supplementary databases may not annotate exactly the same PPI types as the base training data. Our first goal in this paper is to find a method of selecting likely positive data from such supplementary databases. Only extracting likely positive data, however, will bias the classification model unless sufficient negative data is also added. Unfortunately, negative data is very hard to obtain because there are no resources that compile such information. Therefore, our second aim is to select such negative data from unlabeled PubMed data. Thirdly, we explore how to exploit these likely positive and negative data. And lastly, we look at the somewhat unrelated question of which term-weighting scheme is most effective for identifying PPI-related articles. RESULTS: To evaluate the performance of our PPI text classifier, we conducted experiments based on the BioCreAtIvE-II IAS dataset. Our results show that adding likely-labeled data generally increases AUC by 3~6%, indicating better ranking ability. Our experiments also show that our newly-proposed term-weighting scheme has the highest AUC among all common weighting schemes. Our final model achieves an F-measure and AUC 2.9% and 5.0% higher than those of the top-ranking system in the IAS challenge. CONCLUSION: Our experiments demonstrate the effectiveness of integrating unlabeled and likely labeled data to augment a PPI text classification system. Our mixed model is suitable for ranking purposes whereas our hierarchical model is better for filtering. In addition, our results indicate that supervised weighting schemes outperform unsupervised ones. Our newly-proposed weighting scheme, TFBRF, which considers documents that do not contain the target word, avoids some of the biases found in traditional weighting schemes. Our experiment results show TFBRF to be the most effective among several other top weighting schemes.

The application of text-to-speech (TTS) conversion has become widely used in recent years. Chinese TTS faces several unique difficulties. The most critical is caused by the lack of word delimiters in written Chinese. This means that Chinese word segmentation (CWS) must be the first step in Chinese TTS. Unfortunately, due to the ambiguous nature of word boundaries in Chinese, even the best CWS systems make serious segmentation errors. Incorrect sentence interpretation causes TTS errors, preventing TTS’s wider use in applications such as automatic customer services or computer reader systems for the visually impaired. In this paper, we propose a novel method that exploits unlabeled internal data to reduce word segmentation errors without using external dictionaries. To demonstrate the generality of our method, we verify our system on the most widely recognized CWS evaluation tool--the SIGHAN bakeoff, which includes datasets in both traditional and simplified Chinese. These datasets are provided by four representative academies or industrial research institutes in HK, Taiwan, Mainland China, and the U.S. Our experimental results show that with only internal data and unlabeled test data, our approach reduces segmentation errors by an average of 15 % compared to the traditional approach. Moreover, our approach achieves comparable performance to the best CWS systems that use external resources. Further analysis shows that our method has the potential to become more accurate as the amount of test data increases. Index Terms: text-to-speech, Chinese word segmentation, segmentation errors, internal unlabeled data

BACKGROUND: Bioinformatics tools for automatic processing of biomedical literature are invaluable for both the design and interpretation of large-scale experiments. Many information extraction (IE) systems that incorporate natural language processing (NLP) techniques have thus been developed for use in the biomedical field. A key IE task in this field is the extraction of biomedical relations, such as protein-protein and gene-disease interactions. However, most biomedical relation extraction systems usually ignore adverbial and prepositional phrases and words identifying location, manner, timing, and condition, which are essential for describing biomedical relations. Semantic role labeling (SRL) is a natural language processing technique that identifies the semantic roles of these words or phrases in sentences and expresses them as predicate-argument structures. We construct a biomedical SRL system called BIOSMILE that uses a maximum entropy (ME) machine-learning model to extract biomedical relations. BIOSMILE is trained on BioProp, our semi-automatic, annotated biomedical proposition bank. Currently, we are focusing on 30 biomedical verbs that are frequently used or considered important for describing molecular events. RESULTS: To evaluate the performance of BIOSMILE, we conducted two experiments to (1) compare the performance of SRL systems trained on newswire and biomedical corpora; and (2) examine the effects of using biomedical-specific features. The experimental results show that using BioProp improves the F-score of the SRL system by 21.45% over an SRL system that uses a newswire corpus. It is noteworthy that adding automatically generated template features improves the overall F-score by a further 0.52%. Specifically, ArgM-LOC, ArgM-MNR, and Arg2 achieve statistically significant performance improvements of 3.33%, 2.27%, and 1.44%, respectively. CONCLUSION: We demonstrate the necessity of using a biomedical proposition bank for training SRL systems in the biomedical domain. Besides the different characteristics of biomedical and newswire sentences, factors such as cross-domain framesets and verb usage variations also influence the performance of SRL systems. For argument classification, we find that NE (named entity) features indicating if the target node matches with NEs are not effective, since NEs may match with a node of the parsing tree that does not have semantic role labels in the training set. We therefore incorporate templates composed of specific words, NE types, and POS tags into the SRL system. As a result, the classification accuracy for adjunct arguments, which is especially important for biomedical SRL, is improved significantly.

BACKGROUND: Biomedical named entity recognition (Bio-NER) is a challenging problem because, in general, biomedical named entities of the same category (e.g., proteins and genes) do not follow one standard nomenclature. They have many irregularities and sometimes appear in ambiguous contexts. In recent years, machine-learning (ML) approaches have become increasingly common and now represent the cutting edge of Bio-NER technology. This paper addresses three problems faced by ML-based Bio-NER systems. First, most ML approaches usually employ singleton features that comprise one linguistic property (e.g., the current word is capitalized) and at least one class tag (e.g., B-protein, the beginning of a protein name). However, such features may be insufficient in cases where multiple properties must be considered. Adding conjunction features that contain multiple properties can be beneficial, but it would be infeasible to include all conjunction features in an NER model since memory resources are limited and some features are ineffective. To resolve the problem, we use a sequential forward search algorithm to select an effective set of features. Second, variations in the numerical parts of biomedical terms (e.g., "2" in the biomedical term IL2) cause data sparseness and generate many redundant features. In this case, we apply numerical normalization, which solves the problem by replacing all numerals in a term with one representative numeral to help classify named entities. Third, the assignment of NE tags does not depend solely on the target word's closest neighbors, but may depend on words outside the context window (e.g., a context window of five consists of the current word plus two preceding and two subsequent words). We use global patterns generated by the Smith-Waterman local alignment algorithm to identify such structures and modify the results of our ML-based tagger. This is called pattern-based post-processing. RESULTS: To develop our ML-based Bio-NER system, we employ conditional random fields, which have performed effectively in several well-known tasks, as our underlying ML model. Adding selected conjunction features, applying numerical normalization, and employing pattern-based post-processing improve the F-scores by 1.67%, 1.04%, and 0.57%, respectively. The combined increase of 3.28% yields a total score of 72.98%, which is better than the baseline system that only uses singleton features. CONCLUSION: We demonstrate the benefits of using the sequential forward search algorithm to select effective conjunction feature groups. In addition, we show that numerical normalization can effectively reduce the number of redundant and unseen features. Furthermore, the Smith-Waterman local alignment algorithm can help ML-based Bio-NER deal with difficult cases that need longer context windows.