Neural Network and Random Forest Models in Protein Function Prediction.

Over the past decade, the demand for automated protein function prediction has increased due to the volume of newly sequenced proteins. In this paper, we address the function prediction task by developing an ensemble system automatically assigning Gene Ontology (GO) terms to the given input protein sequence. We develop an ensemble system which combines the GO predictions made by random forest (RF) and neural network (NN) classifiers. Both RF and NN models rely on features derived from BLAST sequence alignments, taxonomy and protein signature analysis tools. In addition, we report on experiments with a NN model that directly analyzes the amino acid sequence as its sole input, using a convolutional layer. The Swiss-Prot database is used as the training and evaluation data. In the CAFA3 evaluation, which relies on experimental verification of the functional predictions, our submitted ensemble model demonstrates competitive performance ranking among top-10 best-performing systems out of over 100 submitted systems. In this paper, we evaluate and further improve the CAFA3-submitted system. Our machine learning models together with the data pre-processing and feature generation tools are publicly available as an open source software at https://github.com/TurkuNLP/CAFA3.

Assisting nurses in care documentation: from automated sentence classification to coherent document structures with subject headings.

BACKGROUND: Up to 35% of nurses' working time is spent on care documentation. We describe the evaluation of a system aimed at assisting nurses in documenting patient care and potentially reducing the documentation workload. Our goal is to enable nurses to write or dictate nursing notes in a narrative manner without having to manually structure their text under subject headings. In the current care classification standard used in the targeted hospital, there are more than 500 subject headings to choose from, making it challenging and time consuming for nurses to use. METHODS: The task of the presented system is to automatically group sentences into paragraphs and assign subject headings. For classification the system relies on a neural network-based text classification model. The nursing notes are initially classified on sentence level. Subsequently coherent paragraphs are constructed from related sentences. RESULTS: Based on a manual evaluation conducted by a group of three domain experts, we find that in about 69% of the paragraphs formed by the system the topics of the sentences are coherent and the assigned paragraph headings correctly describe the topics. We also show that the use of a paragraph merging step reduces the number of paragraphs produced by 23% without affecting the performance of the system. CONCLUSIONS: The study shows that the presented system produces a coherent and logical structure for freely written nursing narratives and has the potential to reduce the time and effort nurses are currently spending on documenting care in hospitals.

Supporting the use of standardized nursing terminologies with automatic subject heading prediction: a comparison of sentence-level text classification methods.

OBJECTIVE: This study focuses on the task of automatically assigning standardized (topical) subject headings to free-text sentences in clinical nursing notes. The underlying motivation is to support nurses when they document patient care by developing a computer system that can assist in incorporating suitable subject headings that reflect the documented topics. Central in this study is performance evaluation of several text classification methods to assess the feasibility of developing such a system. MATERIALS AND METHODS: Seven text classification methods are evaluated using a corpus of approximately 0.5 million nursing notes (5.5 million sentences) with 676 unique headings extracted from a Finnish university hospital. Several of these methods are based on artificial neural networks. Evaluation is first done in an automatic manner for all methods, then a manual error analysis is done on a sample. RESULTS: We find that a method based on a bidirectional long short-term memory network performs best with an average recall of 0.5435 when allowed to suggest 1 subject heading per sentence and 0.8954 when allowed to suggest 10 subject headings per sentence. However, other methods achieve comparable results. The manual analysis indicates that the predictions are better than what the automatic evaluation suggests. CONCLUSIONS: The results indicate that several of the tested methods perform well in suggesting the most appropriate subject headings on sentence level. Thus, we find it feasible to develop a text classification system that can support the use of standardized terminologies and save nurses time and effort on care documentation.

Data and systems for medication-related text classification and concept normalization from Twitter: insights from the Social Media Mining for Health (SMM4H)-2017 shared task.

Objective: We executed the Social Media Mining for Health (SMM4H) 2017 shared tasks to enable the community-driven development and large-scale evaluation of automatic text processing methods for the classification and normalization of health-related text from social media. An additional objective was to publicly release manually annotated data. Materials and Methods: We organized 3 independent subtasks: automatic classification of self-reports of 1) adverse drug reactions (ADRs) and 2) medication consumption, from medication-mentioning tweets, and 3) normalization of ADR expressions. Training data consisted of 15 717 annotated tweets for (1), 10 260 for (2), and 6650 ADR phrases and identifiers for (3); and exhibited typical properties of social-media-based health-related texts. Systems were evaluated using 9961, 7513, and 2500 instances for the 3 subtasks, respectively. We evaluated performances of classes of methods and ensembles of system combinations following the shared tasks. Results: Among 55 system runs, the best system scores for the 3 subtasks were 0.435 (ADR class F1-score) for subtask-1, 0.693 (micro-averaged F1-score over two classes) for subtask-2, and 88.5% (accuracy) for subtask-3. Ensembles of system combinations obtained best scores of 0.476, 0.702, and 88.7%, outperforming individual systems. Discussion: Among individual systems, support vector machines and convolutional neural networks showed high performance. Performance gains achieved by ensembles of system combinations suggest that such strategies may be suitable for operational systems relying on difficult text classification tasks (eg, subtask-1). Conclusions: Data imbalance and lack of context remain challenges for natural language processing of social media text. Annotated data from the shared task have been made available as reference standards for future studies (http://dx.doi.org/10.17632/rxwfb3tysd.1).

Wide-scope biomedical named entity recognition and normalization with CRFs, fuzzy matching and character level modeling.

We present a system for automatically identifying a multitude of biomedical entities from the literature. This work is based on our previous efforts in the BioCreative VI: Interactive Bio-ID Assignment shared task in which our system demonstrated state-of-the-art performance with the highest achieved results in named entity recognition. In this paper we describe the original conditional random field-based system used in the shared task as well as experiments conducted since, including better hyperparameter tuning and character level modeling, which led to further performance improvements. For normalizing the mentions into unique identifiers we use fuzzy character n-gram matching. The normalization approach has also been improved with a better abbreviation resolution method and stricter guideline compliance resulting in vastly improved results for various entity types. All tools and models used for both named entity recognition and normalization are publicly available under open license.Database URL: https://github.com/TurkuNLP/BioCreativeVI_BioID_assignment.

An expanded evaluation of protein function prediction methods shows an improvement in accuracy.

BACKGROUND: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. RESULTS: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. CONCLUSIONS: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.

Filtering large-scale event collections using a combination of supervised and unsupervised learning for event trigger classification.

BACKGROUND: Biomedical event extraction is one of the key tasks in biomedical text mining, supporting various applications such as database curation and hypothesis generation. Several systems, some of which have been applied at a large scale, have been introduced to solve this task. Past studies have shown that the identification of the phrases describing biological processes, also known as trigger detection, is a crucial part of event extraction, and notable overall performance gains can be obtained by solely focusing on this sub-task. In this paper we propose a novel approach for filtering falsely identified triggers from large-scale event databases, thus improving the quality of knowledge extraction. METHODS: Our method relies on state-of-the-art word embeddings, event statistics gathered from the whole biomedical literature, and both supervised and unsupervised machine learning techniques. We focus on EVEX, an event database covering the whole PubMed and PubMed Central Open Access literature containing more than 40 million extracted events. The top most frequent EVEX trigger words are hierarchically clustered, and the resulting cluster tree is pruned to identify words that can never act as triggers regardless of their context. For rarely occurring trigger words we introduce a supervised approach trained on the combination of trigger word classification produced by the unsupervised clustering method and manual annotation. RESULTS: The method is evaluated on the official test set of BioNLP Shared Task on Event Extraction. The evaluation shows that the method can be used to improve the performance of the state-of-the-art event extraction systems. This successful effort also translates into removing 1,338,075 of potentially incorrect events from EVEX, thus greatly improving the quality of the data. The method is not solely bound to the EVEX resource and can be thus used to improve the quality of any event extraction system or database. AVAILABILITY: The data and source code for this work are available at: http://bionlp-www.utu.fi/trigger-clustering/.

Application of the EVEX resource to event extraction and network construction: Shared Task entry and result analysis.

BACKGROUND: Modern methods for mining biomolecular interactions from literature typically make predictions based solely on the immediate textual context, in effect a single sentence. No prior work has been published on extending this context to the information automatically gathered from the whole biomedical literature. Thus, our motivation for this study is to explore whether mutually supporting evidence, aggregated across several documents can be utilized to improve the performance of the state-of-the-art event extraction systems. RESULTS: In the GE task, our re-ranking approach led to a modest performance increase and resulted in the first rank of the official Shared Task results with 50.97% F-score. Additionally, in this paper we explore and evaluate the usage of distributed vector representations for this challenge. CONCLUSIONS: For the GRN task, we were able to produce a gene regulatory network from the EVEX data, warranting the use of such generic large-scale text mining data in network biology settings. A detailed performance and error analysis provides more insight into the relatively low recall rates.

Large-scale event extraction from literature with multi-level gene normalization.

Text mining for the life sciences aims to aid database curation, knowledge summarization and information retrieval through the automated processing of biomedical texts. To provide comprehensive coverage and enable full integration with existing biomolecular database records, it is crucial that text mining tools scale up to millions of articles and that their analyses can be unambiguously linked to information recorded in resources such as UniProt, KEGG, BioGRID and NCBI databases. In this study, we investigate how fully automated text mining of complex biomolecular events can be augmented with a normalization strategy that identifies biological concepts in text, mapping them to identifiers at varying levels of granularity, ranging from canonicalized symbols to unique gene and proteins and broad gene families. To this end, we have combined two state-of-the-art text mining components, previously evaluated on two community-wide challenges, and have extended and improved upon these methods by exploiting their complementary nature. Using these systems, we perform normalization and event extraction to create a large-scale resource that is publicly available, unique in semantic scope, and covers all 21.9 million PubMed abstracts and 460 thousand PubMed Central open access full-text articles. This dataset contains 40 million biomolecular events involving 76 million gene/protein mentions, linked to 122 thousand distinct genes from 5032 species across the full taxonomic tree. Detailed evaluations and analyses reveal promising results for application of this data in database and pathway curation efforts. The main software components used in this study are released under an open-source license. Further, the resulting dataset is freely accessible through a novel API, providing programmatic and customized access (http://www.evexdb.org/api/v001/). Finally, to allow for large-scale bioinformatic analyses, the entire resource is available for bulk download from http://evexdb.org/download/, under the Creative Commons - Attribution - Share Alike (CC BY-SA) license.

Exploring Biomolecular Literature with EVEX: Connecting Genes through Events, Homology, and Indirect Associations.

Technological advancements in the field of genetics have led not only to an abundance of experimental data, but also caused an exponential increase of the number of published biomolecular studies. Text mining is widely accepted as a promising technique to help researchers in the life sciences deal with the amount of available literature. This paper presents a freely available web application built on top of 21.3 million detailed biomolecular events extracted from all PubMed abstracts. These text mining results were generated by a state-of-the-art event extraction system and enriched with gene family associations and abstract generalizations, accounting for lexical variants and synonymy. The EVEX resource locates relevant literature on phosphorylation, regulation targets, binding partners, and several other biomolecular events and assigns confidence values to these events. The search function accepts official gene/protein symbols as well as common names from all species. Finally, the web application is a powerful tool for generating homology-based hypotheses as well as novel, indirect associations between genes and proteins such as coregulators.