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Abstract Correction to A. Lourenço, M. Conover, A. Wong, A. Nematzadeh, F. Pan, H. Shatkay, and L.M. Rocha."A Linear Classifier Based on Entity Recognition Tools and a Statistical Approach to Method Extraction in the Protein-Protein Interaction Literature". BMC Bioinformatics 2011, 12(Suppl 8):S12. doi:http://10.1186/1471-2105-12-S8-S12.

Abstract Background While biomedical text mining is emerging as an important research area, practical results have proven difficult to achieve. We believe that an important first step towards more accurate text-mining lies in the ability to identify and characterize text that satisfies various types of information needs. We report here the results of our inquiry into properties of scientific text that have sufficient generality to transcend the confines of a narrow subject area, while supporting practical mining of text for factual information. Our ultimate goal is to annotate a significant corpus of biomedical text and train machine learning methods to automatically categorize such text along certain dimensions that we have defined. Results We have identified five qualitative dimensions that we believe characterize a broad range of scientific sentences, and are therefore useful for supporting a general approach to text-mining: focus, polarity, certainty, evidence, and directionality. We define these dimensions and describe the guidelines we have developed for annotating text with regard to them. To examine the effectiveness of the guidelines, twelve annotators independently annotated the same set of 101 sentences that were randomly selected from current biomedical periodicals. Analysis of these annotations shows 70–80% inter-annotator agreement, suggesting that our guidelines indeed present a well-defined, executable and reproducible task. Conclusion We present our guidelines defining a text annotation task, along with annotation results from multiple independently produced annotations, demonstrating the feasibility of the task. The annotation of a very large corpus of documents along these guidelines is currently ongoing. These annotations form the basis for the categorization of text along multiple dimensions, to support viable text mining for experimental results, methodology statements, and other forms of information. We are currently developing machine learning methods, to be trained and tested on the annotated corpus, that would allow for the automatic categorization of biomedical text along the general dimensions that we have presented. The guidelines in full detail, along with annotated examples, are publicly available.

Abstract Background Experimental techniques such as DNA microarray, serial analysis of gene expression (SAGE) and mass spectrometry proteomics, among others, are generating large amounts of data related to genes and proteins at different levels. As in any other experimental approach, it is necessary to analyze these data in the context of previously known information about the biological entities under study. The literature is a particularly valuable source of information for experiment validation and interpretation. Therefore, the development of automated text mining tools to assist in such interpretation is one of the main challenges in current bioinformatics research. Results We present a method to create literature profiles for large sets of genes or proteins based on common semantic features extracted from a corpus of relevant documents. These profiles can be used to establish pair-wise similarities among genes, utilized in gene/protein classification or can be even combined with experimental measurements. Semantic features can be used by researchers to facilitate the understanding of the commonalities indicated by experimental results. Our approach is based on non-negative matrix factorization (NMF), a machine-learning algorithm for data analysis, capable of identifying local patterns that characterize a subset of the data. The literature is thus used to establish putative relationships among subsets of genes or proteins and to provide coherent justification for this clustering into subsets. We demonstrate the utility of the method by applying it to two independent and vastly different sets of genes. Conclusion The presented method can create literature profiles from documents relevant to sets of genes. The representation of genes as additive linear combinations of semantic features allows for the exploration of functional associations as well as for clustering, suggesting a valuable methodology for the validation and interpretation of high-throughput experimental data.

Motivation: Figures in biomedical papers communicate essential information with the potential to identify relevant documents in biomedical and clinical settings. However, academic search interfaces mainly search over text fields., Results: We describe a search system for biomedical documents that leverages image modalities and an existing index server. We integrate a problem-specific taxonomy of image modalities and image-based data into a custom search system. Our solution features a front-end interface to enhance classical document search results with image-related data, including page thumbnails, figures, captions and image-modality information. We demonstrate the system on a subset of the CORD-19 document collection. A quantitative evaluation demonstrates higher precision and recall for biomedical document retrieval. A qualitative evaluation with domain experts further highlights our solution's benefits to biomedical search., Availability and Implementation: A demonstration is available at https://runachay.evl.uic.edu/scholar. Our code and image models can be accessed via github.com/uic-evl/bio-search. The dataset is continuously expanded., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: Abnormalities in impulse propagation and cardiac repolarization are frequent in hypertrophic cardiomyopathy (HCM), leading to abnormalities in 12-lead electrocardiograms (ECGs). Computational ECG analysis can identify electrophysiological and structural remodeling and predict arrhythmias. This requires accurate ECG segmentation. It is unknown whether current segmentation methods developed using datasets containing annotations for mostly normal heartbeats perform well in HCM. Here, we present a segmentation method to effectively identify ECG waves across 12-lead HCM ECGs., Methods: We develop (1) a web-based tool that permits manual annotations of P, P', QRS, R', S', T, T', U, J, epsilon waves, QRS complex slurring, and atrial fibrillation by 3 experts and (2) an easy-to-implement segmentation method that effectively identifies ECG waves in normal and abnormal heartbeats. Our method was tested on 131 12-lead HCM ECGs and 2 public ECG sets to evaluate its performance in non-HCM ECGs., Results: Over the HCM dataset, our method obtained a sensitivity of 99.2% and 98.1% and a positive predictive value of 92% and 95.3% when detecting QRS complex and T-offset, respectively, significantly outperforming a state-of-the-art segmentation method previously employed for HCM analysis. Over public ECG sets, it significantly outperformed 3 state-of-the-art methods when detecting P-onset and peak, T-offset, and QRS-onset and peak regarding the positive predictive value and segmentation error. It performed at a level similar to other methods in other tasks., Conclusion: Our method accurately identified ECG waves in the HCM dataset, outperforming a state-of-the-art method, and demonstrated similar good performance as other methods in normal/non-HCM ECG sets., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This work proposes a domain-informed neural network architecture for experimental particle physics, using particle interaction localization with the time-projection chamber (TPC) technology for dark matter research as an example application. A key feature of the signals generated within the TPC is that they allow localization of particle interactions through a process called reconstruction (i.e., inverse-problem regression). While multilayer perceptrons (MLPs) have emerged as a leading contender for reconstruction in TPCs, such a black-box approach does not reflect prior knowledge of the underlying scientific processes. This paper looks anew at neural network-based interaction localization and encodes prior detector knowledge, in terms of both signal characteristics and detector geometry, into the feature encoding and the output layers of a multilayer (deep) neural network. The resulting neural network, termed Domain-informed Neural Network (DiNN), limits the receptive fields of the neurons in the initial feature encoding layers in order to account for the spatially localized nature of the signals produced within the TPC. This aspect of the DiNN, which has similarities with the emerging area of graph neural networks in that the neurons in the initial layers only connect to a handful of neurons in their succeeding layer, significantly reduces the number of parameters in the network in comparison to an MLP. In addition, in order to account for the detector geometry, the output layers of the network are modified using two geometric transformations to ensure the DiNN produces localizations within the interior of the detector. The end result is a neural network architecture that has 60% fewer parameters than an MLP, but that still achieves similar localization performance and provides a path to future architectural developments with improved performance because of their ability to encode additional domain knowledge into the architecture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, Higuera, Peters, Roy, Bajwa, Shatkay and Tunnell.)

The discovery of drug-drug interactions (DDIs) that have a translational impact among in vitro pharmacokinetics (PK), in vivo PK and clinical outcomes depends largely on the quality of the annotated corpus available for text mining. We have developed a new DDI corpus based on an annotation scheme that builds upon and extends previous ones, where an abstract is fragmented and each fragment is then annotated along eight dimensions, namely, focus, polarity, certainty, evidence, directionality, study type, interaction type and mechanism. The guideline for defining these dimensions has undergone refinement during the annotation process. Our DDI corpus comprises 900 positive DDI abstracts and 750 that are not directly relevant to DDI. The abstracts in corpus are separated into eight categories of DDI or non-DDI evidence: DDI with pharmacokinetic (PK) mechanism, in vivo DDI PK, DDI clinical, drug-nutrition interaction, single drug, not drug related, in vitro pharmacodynamic (PD) and case report. Seven annotators, three annotators with drug-interaction research experience and four annotators with less drug-interaction research experience independently annotated the DDI corpus, where two researchers independently annotated each abstract. After two rounds of annotations with additional training in between, agreement improved from (0.79, 0.96, 0.86, 0.70, 0.91, 0.65, 0.78, 0.90) to (0.93, 0.99, 0.96, 0.94, 0.95, 0.93, 0.96, 0.97) for focus, certainty, evidence, study type, interaction type, mechanisms, polarity and direction, respectively. The novice-level annotators improved from 0.83 to 0.96, while the expert-level annotators stayed in high performance with some improvement, from 0.90 to 0.96. In summary, we achieved 96% agreement among each pair of annotators with regard to the eight dimensions. The annotated corpus is now available to the community for inclusion in their text-mining pipelines. Database URL https://github.com/zha204/DDI-Corpus-Database/tree/master/DDI%20corpus., (© The Author(s) 2022. Published by Oxford University Press.)

Motivation: Biomedical research findings are typically disseminated through publications. To simplify access to domain-specific knowledge while supporting the research community, several biomedical databases devote significant effort to manual curation of the literature-a labor intensive process. The first step toward biocuration requires identifying articles relevant to the specific area on which the database focuses. Thus, automatically identifying publications relevant to a specific topic within a large volume of publications is an important task toward expediting the biocuration process and, in turn, biomedical research. Current methods focus on textual contents, typically extracted from the title-and-abstract. Notably, images and captions are often used in publications to convey pivotal evidence about processes, experiments and results., Results: We present a new document classification scheme, using both image and caption information, in addition to titles-and-abstracts. To use the image information, we introduce a new image representation, namely Figure-word, based on class labels of subfigures. We use word embeddings for representing captions and titles-and-abstracts. To utilize all three types of information, we introduce two information integration methods. The first combines Figure-words and textual features obtained from captions and titles-and-abstracts into a single larger vector for document representation; the second employs a meta-classification scheme. Our experiments and results demonstrate the usefulness of the newly proposed Figure-words for representing images. Moreover, the results showcase the value of Figure-words, captions and titles-and-abstracts in providing complementary information for document classification; these three sources of information when combined, lead to an overall improved classification performance., Availability and Implementation: Source code and the list of PMIDs of the publications in our datasets are available upon request., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Hypertrophic cardiomyopathy (HCM) patients have a high incidence of atrial fibrillation (AF) and increased stroke risk, even with low CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age diabetes, previous stroke/transient ischemic attack) scores. Hence, there is a need to understand the pathophysiology of AF/stroke in HCM. In this retrospective study, we develop and apply a data-driven, machine learning-based method to identify AF cases, and clinical/imaging features associated with AF, using electronic health record data., Methods: HCM patients with documented paroxysmal/persistent/permanent AF (n = 191) were considered AF cases, and the remaining patients in sinus rhythm (n = 640) were tagged as No-AF. We evaluated 93 clinical variables; the most informative variables useful for distinguishing AF from No-AF cases were selected based on the 2-sample t test and the information gain criterion., Results: We identified 18 highly informative variables that are positively (n = 11) and negatively (n = 7) correlated with AF in HCM. Next, patient records were represented via these 18 variables. Data imbalance resulting from the relatively low number of AF cases was addressed via a combination of oversampling and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. Specifically, an ensemble of logistic regression and naïve Bayes classifiers, trained based on the 18 variables and corrected for data imbalance, proved most effective for separating AF from No-AF cases (sensitivity = 0.74, specificity = 0.70, C-index = 0.80)., Conclusions: Our model (HCM-AF-Risk Model) is the first machine learning-based method for identification of AF cases in HCM. This model demonstrates good performance, addresses data imbalance, and suggests that AF is associated with a more severe cardiac HCM phenotype., (© 2021 The Authors.)

Prostate cancer (PCa) is a common, serious form of cancer in men that is still prevalent despite ongoing developments in diagnostic oncology. Current detection methods lead to high rates of inaccurate diagnosis. We present a method to directly model and exploit temporal aspects of temporal enhanced ultrasound (TeUS) for tissue characterization, which improves malignancy prediction. We employ a probabilistic-temporal framework, namely, hidden Markov models (HMMs), for modeling TeUS data obtained from PCa patients. We distinguish malignant from benign tissue by comparing the respective log-likelihood estimates generated by the HMMs. We analyze 1100 TeUS signals acquired from 12 patients. Our results show improved malignancy identification compared to previous results, demonstrating over 85% accuracy and AUC of 0.95. Incorporating temporal information directly into the models leads to improved tissue differentiation in PCa. We expect our method to generalize and be applied to other types of cancer in which temporal-ultrasound can be recorded.

Clinical translation of drug-drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and link them to clinical consequences. Consequently, we developed information retrieval (IR) models to retrieve DDI and drug-gene interaction (DGI) evidence from 25 million PubMed abstracts and distinguish DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for US Food and Drug Administration (FDA) approved and withdrawn drugs. Additionally, information extraction models were developed to extract DDI-pairs and DGI-pairs from the IR-retrieved abstracts. An overlapping analysis identified 986 unique DDI-pairs between all 3 types of evidence. Another 2,157 and 13,012 DDI-pairs and 3,173 DGI-pairs were identified from known clinical PK/PD DDI, clinical PD DDI, and DGI evidence, respectively. By integrating DDI and DGI evidence, we discovered 119 and 18 new pharmacogenetic hypotheses associated with CYP3A and CYP2D6, respectively. Some of these DGI evidence can also aid us in understanding DDI mechanisms., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Gathering information from the scientific literature is essential for biomedical research, as much knowledge is conveyed through publications. However, the large and rapidly increasing publication rate makes it impractical for researchers to quickly identify all and only those documents related to their interest. As such, automated biomedical document classification attracts much interest. Such classification is critical in the curation of biological databases, because biocurators must scan through a vast number of articles to identify pertinent information within documents most relevant to the database. This is a slow, labor-intensive process that can benefit from effective automation., We present a document classification scheme aiming to identify papers containing information relevant to a specific topic, among a large collection of articles, for supporting the biocuration classification task. Our framework is based on a meta-classification scheme we have introduced before; here we incorporate into it features gathered from figure captions, in addition to those obtained from titles and abstracts. We trained and tested our classifier over a large imbalanced dataset, originally curated by the Gene Expression Database (GXD). GXD collects all the gene expression information in the Mouse Genome Informatics (MGI) resource. As part of the MGI literature classification pipeline, GXD curators identify MGI-selected papers that are relevant for GXD. The dataset consists of ~60 000 documents (5469 labeled as relevant; 52 866 as irrelevant), gathered throughout 2012-2016, in which each document is represented by the text of its title, abstract and figure captions. Our classifier attains precision 0.698, recall 0.784, f-measure 0.738 and Matthews correlation coefficient 0.711, demonstrating that the proposed framework effectively addresses the high imbalance in the GXD classification task. Moreover, our classifier's performance is significantly improved by utilizing information from image captions compared to using titles and abstracts alone; this observation clearly demonstrates that image captions provide substantial information for supporting biomedical document classification and curation., Database URL., (© The Author(s) 2020. Published by Oxford University Press.)

Motivation: Figures and captions convey essential information in biomedical documents. As such, there is a growing interest in mining published biomedical figures and in utilizing their respective captions as a source of knowledge. Notably, an essential step underlying such mining is the extraction of figures and captions from publications. While several PDF parsing tools that extract information from such documents are publicly available, they attempt to identify images by analyzing the PDF encoding and structure and the complex graphical objects embedded within. As such, they often incorrectly identify figures and captions in scientific publications, whose structure is often non-trivial. The extraction of figures, captions and figure-caption pairs from biomedical publications is thus neither well-studied nor yet well-addressed., Results: We introduce a new and effective system for figure and caption extraction, PDFigCapX. Unlike existing methods, we first separate between text and graphical contents, and then utilize layout information to effectively detect and extract figures and captions. We generate files containing the figures and their associated captions and provide those as output to the end-user.We test our system both over a public dataset of computer science documents previously used by others, and over two newly collected sets of publications focusing on the biomedical domain. Our experiments and results comparing PDFigCapX to other state-of-the-art systems show a significant improvement in performance, and demonstrate the effectiveness and robustness of our approach., Availability and Implementation: Our system is publicly available for use at: https://www.eecis.udel.edu/~compbio/PDFigCapX. The two new datasets are available at: https://www.eecis.udel.edu/~compbio/PDFigCapX/Downloads., (© The Author(s) 2019. Published by Oxford University Press.)

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample ttest and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naïve Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes. Our model demonstrates good performance (C-index) compared with currently employed SCD prediction algorithms, while addressing imbalance inherent in clinical data., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Published literature is an important source of knowledge supporting biomedical research. Given the large and increasing number of publications, automated document classification plays an important role in biomedical research. Effective biomedical document classifiers are especially needed for bio-databases, in which the information stems from many thousands of biomedical publications that curators must read in detail and annotate. In addition, biomedical document classification often amounts to identifying a small subset of relevant publications within a much larger collection of available documents. As such, addressing class imbalance is essential to a practical classifier. We present here an effective classification scheme for automatically identifying papers among a large pool of biomedical publications that contain information relevant to a specific topic, which the curators are interested in annotating. The proposed scheme is based on a meta-classification framework using cluster-based under-sampling combined with named-entity recognition and statistical feature selection strategies. We examined the performance of our method over a large imbalanced data set that was originally manually curated by the Jackson Laboratory's Gene Expression Database (GXD). The set consists of more than 90 000 PubMed abstracts, of which about 13 000 documents are labeled as relevant to GXD while the others are not relevant. Our results, 0.72 precision, 0.80 recall and 0.75 f-measure, demonstrate that our proposed classification scheme effectively categorizes such a large data set in the face of data imbalance., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Chronic Kidney Disease (CKD) is one of several conditions that affect a growing percentage of the US population; the disease is accompanied by multiple co-morbidities, and is hard to diagnose in-and-of itself. In its advanced forms it carries severe outcomes and can lead to death. It is thus important to detect the disease as early as possible, which can help devise effective intervention and treatment plan. Here we investigate ways to utilize information available in electronic health records (EHRs) from regular office visits of more than 13,000 patients, in order to distinguish among several stages of the disease. While clinical data stored in EHRs provide valuable information for risk-stratification, one of the major challenges in using them arises from data imbalance. That is, records associated with a more severe condition are typically under-represented compared to those associated with a milder manifestation of the disease. To address imbalance, we propose and develop a sampling-based ensemble approach, hierarchical meta-classification, aiming to stratify CKD patients into severity stages, using simple quantitative non-text features gathered from standard office visit records., Methods: The proposed hierarchical meta-classification method frames the multiclass classification task as a hierarchy of two subtasks. The first is binary classification, separating records associated with the majority class from those associated with all minority classes combined, using meta-classification. The second subtask separates the records assigned to the combined minority classes into the individual constituent classes., Results: The proposed method identifies a significant proportion of patients suffering from the more advanced stages of the condition, while also correctly identifying most of the less severe cases, maintaining high sensitivity, specificity and F-measure (≥ 93%). Our results show that the high level of performance attained by our method is preserved even when the size of the training set is significantly reduced, demonstrating the stability and generalizability of our approach., Conclusion: We present a new approach to perform classification while addressing data imbalance, which is inherent in the biomedical domain. Our model effectively identifies severity stages of CKD patients, using information readily available in office visit records within the realistic context of high data imbalance.

Little is known about the characteristics and function of reproductive phased, secondary, small interfering RNAs (phasiRNAs) in the Poaceae, despite the availability of significant genomic resources, experimental data, and a growing number of computational tools. We utilized machine-learning methods to identify sequence-based and positional features that distinguish phasiRNAs in rice and maize from other small RNAs (sRNAs). We developed Random Forest classifiers that can distinguish reproductive phasiRNAs from other sRNAs in complex sets of sequencing data, utilizing sequence-based (k-mers) and features describing position-specific sequence biases. The classification performance attained is > 80% in accuracy, sensitivity, specificity, and positive predicted value. Feature selection identified important features in both ends of phasiRNAs. We demonstrated that phasiRNAs have strand specificity and position-specific nucleotide biases potentially influencing AGO sorting; we also predicted targets to infer functions of phasiRNAs, and computationally assessed their sequence characteristics relative to other sRNAs. Our results demonstrate that machine-learning methods effectively identify phasiRNAs despite the lack of characteristic features typically present in precursor loci of other small RNAs, such as sequence conservation or structural motifs. The 5'-end features we identified provide insights into AGO-phasiRNA interactions. We describe a hypothetical model of competition for AGO loading between phasiRNAs of different nucleotide compositions., (© 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.)

Objectives: Temporal enhanced ultrasound (TeUS) is a new ultrasound-based imaging technique that provides tissue-specific information. Recent studies have shown the potential of TeUS for improving tissue characterization in prostate cancer diagnosis. We study the temporal properties of TeUS-temporal order and length-and present a new framework to assess their impact on tissue information., Methods: We utilize a probabilistic modeling approach using hidden Markov models (HMMs) to capture the temporal signatures of malignant and benign tissues from TeUS signals of nine patients. We model signals of benign and malignant tissues (284 and 286 signals, respectively) in their original temporal order as well as under order permutations. We then compare the resulting models using the Kullback-Liebler divergence and assess their performance differences in characterization. Moreover, we train HMMs using TeUS signals of different durations and compare their model performance when differentiating tissue types., Results: Our findings demonstrate that models of order-preserved signals perform statistically significantly better (85% accuracy) in tissue characterization compared to models of order-altered signals (62% accuracy). The performance degrades as more changes in signal order are introduced. Additionally, models trained on shorter sequences perform as accurately as models of longer sequences., Conclusion: The work presented here strongly indicates that temporal order has substantial impact on TeUS performance; thus, it plays a significant role in conveying tissue-specific information. Furthermore, shorter TeUS signals can relay sufficient information to accurately distinguish between tissue types., Significance: Understanding the impact of TeUS properties facilitates the process of its adopting in diagnostic procedures and provides insights on improving its acquisition.

Patients associated with multiple co-occurring health conditions often face aggravated complications and less favorable outcomes. Co-occurring conditions are especially prevalent among individuals suffering from kidney disease, an increasingly widespread condition affecting 13% of the general population in the US. This study aims to identify and characterize patterns of co-occurring medical conditions in patients employing a probabilistic framework. Specifically, we apply topic modeling in a non-traditional way to find associations across SNOMED-CT codes assigned and recorded in the EHRs of >13,000 patients diagnosed with kidney disease. Unlike most prior work on topic modeling, we apply the method to codes rather than to natural language. Moreover, we quantitatively evaluate the topics, assessing their tightness and distinctiveness, and also assess the medical validity of our results. Our experiments show that each topic is succinctly characterized by a few highly probable and unique disease codes, indicating that the topics are tight. Furthermore, inter-topic distance between each pair of topics is typically high, illustrating distinctiveness. Last, most coded conditions grouped together within a topic, are indeed reported to co-occur in the medical literature. Notably, our results uncover a few indirect associations among conditions that have hitherto not been reported as correlated in the medical literature., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Motivation: Images convey essential information in biomedical publications. As such, there is a growing interest within the bio-curation and the bio-databases communities, to store images within publications as evidence for biomedical processes and for experimental results. However, many of the images in biomedical publications are compound images consisting of multiple panels, where each individual panel potentially conveys a different type of information. Segmenting such images into constituent panels is an essential first step toward utilizing images., Results: In this article, we develop a new compound image segmentation system, FigSplit, which is based on Connected Component Analysis. To overcome shortcomings typically manifested by existing methods, we develop a quality assessment step for evaluating and modifying segmentations. Two methods are proposed to re-segment the images if the initial segmentation is inaccurate. Experimental results show the effectiveness of our method compared with other methods., Availability and Implementation: The system is publicly available for use at: https://www.eecis.udel.edu/~compbio/FigSplit. The code is available upon request., Contact: shatkay@udel.edu., Supplementary Information: Supplementary data are available online at Bioinformatics.

Many of the figures in biomedical publications are compound figures consisting of multiple panels. Segmenting such figures into constituent panels is an essential first step for harvesting the visual information within the biomedical documents. Current figure separation methods are based primarily on gap-detection and suffer from over- and under-segmentation. In this paper, we propose a new compound figure segmentation scheme based on Connected Component Analysis. To overcome shortcomings typically manifested by existing methods, we develop a quality assessment step for evaluating and modifying segmentations. Two methods are proposed to re-segment the images if the initial segmentations are inaccurate. Experiments and results comparing the performance of our method to that of other top methods demonstrate the effectiveness of our approach.

The Gene Expression Database (GXD) is a comprehensive online database within the Mouse Genome Informatics resource, aiming to provide available information about endogenous gene expression during mouse development. The information stems primarily from many thousands of biomedical publications that database curators must go through and read. Given the very large number of biomedical papers published each year, automatic document classification plays an important role in biomedical research. Specifically, an effective and efficient document classifier is needed for supporting the GXD annotation workflow. We present here an effective yet relatively simple classification scheme, which uses readily available tools while employing feature selection, aiming to assist curators in identifying publications relevant to GXD. We examine the performance of our method over a large manually curated dataset, consisting of more than 25 000 PubMed abstracts, of which about half are curated as relevant to GXD while the other half as irrelevant to GXD. In addition to text from title-and-abstract, we also consider image captions, an important information source that we integrate into our method. We apply a captions-based classifier to a subset of about 3300 documents, for which the full text of the curated articles is available. The results demonstrate that our proposed approach is robust and effectively addresses the GXD document classification. Moreover, using information obtained from image captions clearly improves performance, compared to title and abstract alone, affirming the utility of image captions as a substantial evidence source for automatically determining the relevance of biomedical publications to a specific subject area., Database Url: www.informatics.jax.org., (© The Author(s) 2017. Published by Oxford University Press.)

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease where the heart muscle is partially thickened and blood flow is (potentially fatally) obstructed. A test based on electrocardiograms (ECG) that record the heart electrical activity can help in early detection of HCM patients. This paper presents a cardiovascular-patient classifier we developed to identify HCM patients using standard 10-second, 12-lead ECG signals. Patients are classified as having HCM if the majority of their recorded heartbeats are recognized as characteristic of HCM. Thus, the classifier's underlying task is to recognize individual heartbeats segmented from 12-lead ECG signals as HCM beats, where heartbeats from non-HCM cardiovascular patients are used as controls. We extracted 504 morphological and temporal features—both commonly used and newly-developed ones—from ECG signals for heartbeat classification. To assess classification performance, we trained and tested a random forest classifier and a support vector machine classifier using 5-fold cross validation. We also compared the performance of these two classifiers to that obtained by a logistic regression classifier, and the first two methods performed better than logistic regression. The patient-classification precision of random forests and of support vector machine classifiers is close to 0.85. Recall (sensitivity) and specificity are approximately 0.90. We also conducted feature selection experiments by gradually removing the least informative features; the results show that a relatively small subset of 264 highly informative features can achieve performance measures comparable to those achieved by using the complete set of features.

Motivation: Proteins are responsible for a multitude of vital tasks in all living organisms. Given that a protein's function and role are strongly related to its subcellular location, protein location prediction is an important research area. While proteins move from one location to another and can localize to multiple locations, most existing location prediction systems assign only a single location per protein. A few recent systems attempt to predict multiple locations for proteins, however, their performance leaves much room for improvement. Moreover, such systems do not capture dependencies among locations and usually consider locations as independent. We hypothesize that a multi-location predictor that captures location inter-dependencies can improve location predictions for proteins., Results: We introduce a probabilistic generative model for protein localization, and develop a system based on it-which we call MDLoc-that utilizes inter-dependencies among locations to predict multiple locations for proteins. The model captures location inter-dependencies using Bayesian networks and represents dependency between features and locations using a mixture model. We use iterative processes for learning model parameters and for estimating protein locations. We evaluate our classifier MDLoc, on a dataset of single- and multi-localized proteins derived from the DBMLoc dataset, which is the most comprehensive protein multi-localization dataset currently available. Our results, obtained by using MDLoc, significantly improve upon results obtained by an initial simpler classifier, as well as on results reported by other top systems., Availability and Implementation: MDLoc is available at: http://www.eecis.udel.edu/∼compbio/mdloc., (© The Author 2015. Published by Oxford University Press.)

The current era of large-scale biology is characterized by a fast-paced growth in the number of sequenced genomes and, consequently, by a multitude of identified proteins whose function has yet to be determined. Simultaneously, any known or postulated information concerning genes and proteins is part of the ever-growing published scientific literature, which is expanding at a rate of over a million new publications per year. Computational tools that attempt to automatically predict and annotate protein characteristics, such as function and localization patterns, are being developed along with systems that aim to support the process via text mining. Most work on protein characterization focuses on features derived directly from protein sequence data. Protein-related work that does aim to utilize the literature typically concentrates on extracting specific facts (e.g., protein interactions) from text. In the past few years we have taken a different route, treating the literature as a source of text-based features, which can be employed just as sequence-based protein-features were used in earlier work, for predicting protein subcellular location and possibly also function. We discuss here in detail the overall approach, along with results from work we have done in this area demonstrating the value of this method and its potential use., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The ISMB Special Interest Group on Linking Literature, Information and Knowledge for Biology (BioLINK) organized a one-day workshop at ISMB/ECCB 2013 in Berlin, Germany. The theme of the workshop was 'Roles for text mining in biomedical knowledge discovery and translational medicine'. This summary reviews the outcomes of the workshop. Meeting themes included concept annotation methods and applications, extraction of biological relationships and the use of text-mined data for biological data analysis., Availability and Implementation: All articles are available at http://biolinksig.org/proceedings-online/., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Test based on electrocardiograms (ECG) that record the heart electrical activity can help in early detection of patients with hypertrophic cardiomyopathy (HCM) where the heart muscle is partially thickened and blood flow is (potentially fatally) obstructed. This paper presents a cardiovascular-patient classifier we developed to identify HCM patients using standard 10-seconds, 12-lead ECG signals. Patients are classified as having HCM if the majority of the heartbeats are recognized as HCM. Thus, the classifier's underlying task is to recognize individual heartbeats segmented from 12-lead ECG signals as HCM beats, where heartbeats from non-HCM cardiovascular patients are used as controls. We extracted 504 morphological and temporal features - both commonly used and newly-developed ones - from ECG signals for heartbeat classification. To assess classification performance, we trained and tested a random forest classifier and a support vector machine classifier using 5-fold cross validation. The patient-classification precision and F-measure of both classifiers are close to 0.85. Recall (sensitivity) and specificity are approximately 0.90. We also conducted feature selection experiments by gradually removing the least informative features; the results show that a relatively small subset of 304 highly informative features can achieve performance measures comparable to that achieved by using the complete set of features.

Motivation: Knowing the location of a protein within the cell is important for understanding its function, role in biological processes, and potential use as a drug target. Much progress has been made in developing computational methods that predict single locations for proteins. Most such methods are based on the over-simplifying assumption that proteins localize to a single location. However, it has been shown that proteins localize to multiple locations. While a few recent systems attempt to predict multiple locations of proteins, their performance leaves much room for improvement. Moreover, they typically treat locations as independent and do not attempt to utilize possible inter-dependencies among locations. Our hypothesis is that directly incorporating inter-dependencies among locations into both the classifier-learning and the prediction process can improve location prediction performance., Results: We present a new method and a preliminary system we have developed that directly incorporates inter-dependencies among locations into the location-prediction process of multiply-localized proteins. Our method is based on a collection of Bayesian network classifiers, where each classifier is used to predict a single location. Learning the structure of each Bayesian network classifier takes into account inter-dependencies among locations, and the prediction process uses estimates involving multiple locations. We evaluate our system on a dataset of single- and multi-localized proteins (the most comprehensive protein multi-localization dataset currently available, derived from the DBMLoc dataset). Our results, obtained by incorporating inter-dependencies, are significantly higher than those obtained by classifiers that do not use inter-dependencies. The performance of our system on multi-localized proteins is comparable to a top performing system (YLoc+), without being restricted only to location-combinations present in the training set.

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

Background: Advances in sequencing technology over the past decade have resulted in an abundance of sequenced proteins whose function is yet unknown. As such, computational systems that can automatically predict and annotate protein function are in demand. Most computational systems use features derived from protein sequence or protein structure to predict function. In an earlier work, we demonstrated the utility of biomedical literature as a source of text features for predicting protein subcellular location. We have also shown that the combination of text-based and sequence-based prediction improves the performance of location predictors. Following up on this work, for the Critical Assessment of Function Annotations (CAFA) Challenge, we developed a text-based system that aims to predict molecular function and biological process (using Gene Ontology terms) for unannotated proteins. In this paper, we present the preliminary work and evaluation that we performed for our system, as part of the CAFA challenge., Results: We have developed a preliminary system that represents proteins using text-based features and predicts protein function using a k-nearest neighbour classifier (Text-KNN). We selected text features for our classifier by extracting key terms from biomedical abstracts based on their statistical properties. The system was trained and tested using 5-fold cross-validation over a dataset of 36,536 proteins. System performance was measured using the standard measures of precision, recall, F-measure and overall accuracy. The performance of our system was compared to two baseline classifiers: one that assigns function based solely on the prior distribution of protein function (Base-Prior) and one that assigns function based on sequence similarity (Base-Seq). The overall prediction accuracy of Text-KNN, Base-Prior, and Base-Seq for molecular function classes are 62%, 43%, and 58% while the overall accuracy for biological process classes are 17%, 11%, and 28% respectively. Results obtained as part of the CAFA evaluation itself on the CAFA dataset are reported as well., Conclusions: Our evaluation shows that the text-based classifier consistently outperforms the baseline classifier that is based on prior distribution, and typically has comparable performance to the baseline classifier that uses sequence similarity. Moreover, the results suggest that combining text features with other types of features can potentially lead to improved prediction performance. The preliminary results also suggest that while our text-based classifier can be used to predict both molecular function and biological process in which a protein is involved, the classifier performs significantly better for predicting molecular function than for predicting biological process. A similar trend was observed for other classifiers participating in the CAFA challenge.

Background: Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them., Results: A total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35%) the macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of 55%., Conclusions: The results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heterogeneity and different granularity of method term concepts encountered in the ontology. However, combining the sophisticated techniques developed by the participants with supporting evidence strings derived from the articles for human interpretation could result in practical modules for biological annotation workflows.