Clinical IE has been used for a wide range of applications, however, there is a considerable gap between clinical studies using EHR data and studies using clinical IE. This study enabled us to gain a more concrete understanding of the gap and to provide potential solutions to bridge this gap.

Based on the evaluation results, we can draw the following conclusions. First, the word embeddings trained from EHR and MedLit can capture the semantics of medical terms better, and find semantically relevant medical terms closer to human experts' judgments than those trained from GloVe and Google News. Second, there does not exist a consistent global ranking of word embeddings for all downstream biomedical NLP applications. However, adding word embeddings as extra features will improve results on most downstream tasks. Finally, the word embeddings trained from the biomedical domain corpora do not necessarily have better performance than those trained from the general domain corpora for any downstream biomedical NLP task.

BackgroundAutomatic clinical text classification is a natural language processing (NLP) technology that unlocks information embedded in clinical narratives. Machine learning approaches have been shown to be effective for clinical text classification tasks. However, a successful machine learning model usually requires extensive human efforts to create labeled training data and conduct feature engineering. In this study, we propose a clinical text classification paradigm using weak supervision and deep representation to reduce these human efforts.MethodsWe develop a rule-based NLP algorithm to automatically generate labels for the training data, and then use the pre-trained word embeddings as deep representation features for training machine learning models. Since machine learning is trained on labels generated by the automatic NLP algorithm, this training process is called weak supervision. We evaluat the paradigm effectiveness on two institutional case studies at Mayo Clinic: smoking status classification and proximal femur (hip) fracture classification, and one case study using a public dataset: the i2b2 2006 smoking status classification shared task. We test four widely used machine learning models, namely, Support Vector Machine (SVM), Random Forest (RF), Multilayer Perceptron Neural Networks (MLPNN), and Convolutional Neural Networks (CNN), using this paradigm. Precision, recall, and F1 score are used as metrics to evaluate performance.ResultsCNN achieves the best performance in both institutional tasks (F1 score: 0.92 for Mayo Clinic smoking status classification and 0.97 for fracture classification). We show that word embeddings significantly outperform tf-idf and topic modeling features in the paradigm, and that CNN captures additional patterns from the weak supervision compared to the rule-based NLP algorithms. We also observe two drawbacks of the proposed paradigm that CNN is more sensitive to the size of training data, and that the proposed paradigm might not be effective for complex multiclass classification tasks.ConclusionThe proposed clinical text classification paradigm could reduce human efforts of labeled training data creation and feature engineering for applying machine learning to clinical text classification by leveraging weak supervision and deep representation. The experimental experiments have validated the effectiveness of paradigm by two institutional and one shared clinical text classification tasks.

BackgroundDomesticated from gray wolves between 10 and 40 kya in Eurasia, dogs display a vast array of phenotypes that differ from their ancestors, yet mirror other domesticated animal species, a phenomenon known as the domestication syndrome. Here, we use signatures persisting in dog genomes to identify genes and pathways possibly altered by the selective pressures of domestication.ResultsWhole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves differentiated signatures resulting from domestication rather than breed formation. We identified 246 candidate domestication regions containing 10.8 Mb of genome sequence and 429 genes. The regions share haplotypes with ancient dogs, suggesting that the detected signals are not the result of recent selection. Gene enrichments highlight numerous genes linked to neural crest and central nervous system development as well as neurological function. Read depth analysis suggests that copy number variation played a minor role in dog domestication.ConclusionsOur results identify genes that act early in embryogenesis and can confer phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development as the targets of selection during domestication. These differences reflect the phenotypes of the domestication syndrome, which can be explained by alterations in the migration or activity of neural crest cells during development. We propose that initial selection during early dog domestication was for behavior, a trait influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.Electronic supplementary materialThe online version of this article (10.1186/s12915-018-0535-2) contains supplementary material, which is available to authorized users.

The wide adoption of electronic health records (EHRs) has enabled a wide range of applications leveraging EHR data. However, the meaningful use of EHR data largely depends on our ability to efficiently extract and consolidate information embedded in clinical text where natural language processing (NLP) techniques are essential. Semantic textual similarity (STS) that measures the semantic similarity between text snippets plays a significant role in many NLP applications. In the general NLP domain, STS shared tasks have made available a huge collection of text snippet pairs with manual annotations in various domains. In the clinical domain, STS can enable us to detect and eliminate redundant information that may lead to a reduction in cognitive burden and an improvement in the clinical decision-making process. This paper elaborates our efforts to assemble a resource for STS in the medical domain, MedSTS. It consists of a total of 174,629 sentence pairs gathered from a clinical corpus at Mayo Clinic. A subset of MedSTS (MedSTS_ann) containing 1,068 sentence pairs was annotated by two medical experts with semantic similarity scores of 0-5 (low to high similarity). We further analyzed the medical concepts in the MedSTS corpus, and tested four STS systems on the MedSTS_ann corpus. In the future, we will organize a shared task by releasing the MedSTS_ann corpus to motivate the community to tackle the real world clinical problems. KeywordsElectronic health records, semantic textual similarity, natural language processing, clinical semantic textual similarity resource 1

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Integration of detailed phenotype information with genetic data is well established to facilitate accurate diagnosis of hereditary disorders. As a rich source of phenotype information, electronic health records (EHRs) promise to empower diagnostic variant interpretation. However, how to accurately and efficiently extract phenotypes from heterogeneous EHR narratives remains a challenge. Here, we present EHR-Phenolyzer, a high-throughput EHR framework for extracting and analyzing phenotypes. EHR-Phenolyzer extracts and normalizes Human Phenotype Ontology (HPO) concepts from EHR narratives and then prioritizes genes with causal variants on the basis of the HPO-coded phenotype manifestations. We assessed EHR-Phenolyzer on 28 pediatric individuals with confirmed diagnoses of monogenic diseases and found that the genes with causal variants were ranked among the top 100 genes selected by EHR-Phenolyzer for 16/28 individuals (p < 2.2 × 10), supporting the value of phenotype-driven gene prioritization in diagnostic sequence interpretation. To assess the generalizability, we replicated this finding on an independent EHR dataset of ten individuals with a positive diagnosis from a different institution. We then assessed the broader utility by examining two additional EHR datasets, including 31 individuals who were suspected of having a Mendelian disease and underwent different types of genetic testing and 20 individuals with positive diagnoses of specific Mendelian etiologies of chronic kidney disease from exome sequencing. Finally, through several retrospective case studies, we demonstrated how combined analyses of genotype data and deep phenotype data from EHRs can expedite genetic diagnoses. In summary, EHR-Phenolyzer leverages EHR narratives to automate phenotype-driven analysis of clinical exomes or genomes, facilitating the broader implementation of genomic medicine.

BackgroundIn the United States, a rare disease is characterized as the one affecting no more than 200,000 patients at a certain period. Patients suffering from rare diseases are often either misdiagnosed or left undiagnosed, possibly due to insufficient knowledge or experience with the rare disease on the part of clinical practitioners. With an exponentially growing volume of electronically accessible medical data, a large volume of information on thousands of rare diseases and their potentially associated diagnostic information is buried in electronic medical records (EMRs) and medical literature.ObjectiveThis study aimed to leverage information contained in heterogeneous datasets to assist rare disease diagnosis. Phenotypic information of patients existed in EMRs and biomedical literature could be fully leveraged to speed up diagnosis of diseases.MethodsIn our previous work, we advanced the use of a collaborative filtering recommendation system to support rare disease diagnostic decision making based on phenotypes derived solely from EMR data. However, the influence of using heterogeneous data with collaborative filtering was not discussed, which is an essential problem while facing large volumes of data from various resources. In this study, to further investigate the performance of collaborative filtering on heterogeneous datasets, we studied EMR data generated at Mayo Clinic as well as published article abstracts retrieved from the Semantic MEDLINE Database. Specifically, in this study, we designed different data fusion strategies from heterogeneous resources and integrated them with the collaborative filtering model.ResultsWe evaluated performance of the proposed system using characterizations derived from various combinations of EMR data and literature, as well as with sole EMR data. We extracted nearly 13 million EMRs from the patient cohort generated between 2010 and 2015 at Mayo Clinic and retrieved all article abstracts from the semistructured Semantic MEDLINE Database that were published till the end of 2016. We applied a collaborative filtering model and compared the performance generated by different metrics. Log likelihood ratio similarity combined with k-nearest neighbor on heterogeneous datasets showed the optimal performance in patient recommendation with area under the precision-recall curve (PRAUC) 0.475 (string match), 0.511 (systematized nomenclature of medicine [SNOMED] match), and 0.752 (Genetic and Rare Diseases Information Center [GARD] match). Log likelihood ratio similarity also performed the best with mean average precision 0.465 (string match), 0.5 (SNOMED match), and 0.749 (GARD match). Performance of rare disease prediction was also demonstrated by using the optimal algorithm. Macro-average F-measure for string, SNOMED, and GARD match were 0.32, 0.42, and 0.63, respectively.ConclusionsThis study demonstrated potential utilization of heterogeneous datasets in a collaborative filtering model to support rare disease diagnosis. In addition to phenotypic-based analysis, in the future, w...