EXACT2: the semantics of biomedical protocols

© 2014 Soldatova et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: The reliability and reproducibility of experimental procedures is a cornerstone of scientific practice. There is a pressing technological need for the better representation of biomedical protocols to enable other agents (human or machine) to better reproduce results. A framework that ensures that all information required for the replication of experimental protocols is essential to achieve reproducibility. Methods: We have developed the ontology EXACT2 (EXperimental ACTions) that is designed to capture the full semantics of biomedical protocols required for their reproducibility. To construct EXACT2 we manually inspected hundreds of published and commercial biomedical protocols from several areas of biomedicine. After establishing a clear pattern for extracting the required information we utilized text-mining tools to translate the protocols into a machine amenable format. We have verified the utility of EXACT2 through the successful processing of previously ‘unseen’ (not used for the construction of EXACT2) protocols. Results: The paper reports on a fundamentally new version EXACT2 that supports the semantically-defined representation of biomedical protocols. The ability of EXACT2 to capture the semantics of biomedical procedures was verified through a text mining use case. In this EXACT2 is used as a reference model for text mining tools to identify terms pertinent to experimental actions, and their properties, in biomedical protocols expressed in natural language. An EXACT2-based framework for the translation of biomedical protocols to a machine amenable format is proposed. Conclusions: The EXACT2 ontology is sufficient to record, in a machine processable form, the essential information about biomedical protocols. EXACT2 defines explicit semantics of experimental actions, and can be used by various computer applications. It can serve as a reference model for for the translation of biomedical protocols in natural language into a semantically-defined format.This work has been partially funded by the Brunel University BRIEF award and a grant from Occams Resources

CREATING A BIOMEDICAL ONTOLOGY INDEXED SEARCH ENGINE TO IMPROVE THE SEMANTIC RELEVANCE OF RETREIVED MEDICAL TEXT

Medical Subject Headings (MeSH) is a controlled vocabulary used by the National Library of Medicine to index medical articles, abstracts, and journals contained within the MEDLINE database. Although MeSH imposes uniformity and consistency in the indexing process, it has been proven that using MeSH indices only result in a small increase in precision over free-text indexing. Moreover, studies have shown that the use of controlled vocabularies in the indexing process is not an effective method to increase semantic relevance in information retrieval. To address the need for semantic relevance, we present an ontology-based information retrieval system for the MEDLINE collection that result in a 37.5% increase in precision when compared to free-text indexing systems. The presented system focuses on the ontology to: provide an alternative to text-representation for medical articles, finding relationships among co-occurring terms in abstracts, and to index terms that appear in text as well as discovered relationships. The presented system is then compared to existing MeSH and Free-Text information retrieval systems. This dissertation provides a proof-of-concept for an online retrieval system capable of providing increased semantic relevance when searching through medical abstracts in MEDLINE

Automatic Identification of Interestingness in Biomedical Literature

This thesis presents research on automatically identifying interestingness in a graph of semantic predications. Interestingness represents a subjective quality of information that represents its value in meeting a user\u27s known or unknown retrieval needs. The perception of information as interesting requires a level of utility for the user as well as a balance between significant novelty and sufficient familiarity. It can also be influenced by additional factors such as unexpectedness or serendipity with recent experiences. The ability to identify interesting information facilitates the development of user-centered retrieval, especially in information semantic summarization and iterative, step-wise searching such as in discovery browsing systems. Ultimately, this allows biomedical researchers to more quickly identify information of greatest potential interest to them, whether expected or, perhaps more importantly, unexpected. Current discovery browsing systems use iterative information retrieval to discover new knowledge - a process that requires finding relevant co-occurring topics and relationships through consistent human involvement to identify interesting concepts. Although interestingness is subjective, this thesis identifies computable quantities in semantic data that correlate to interestingness in user searches. We compare several statistical and rule-based models correlating graph data extracted from semantic predications with concept interestingness as demonstrated in PubMed queries. Semantic predications represent scientific assertions extracted from all of the biomedical literature contained in the MEDLINE database. They are of the form, subject-predicate-object . Predications can easily be represented as graphs, where subjects and objects are nodes and predicates form edges. A graph of predications represents the assertions made in the citations from which the predications were extracted. This thesis uses graph metrics to identify features from the predication graph for model generation. These features are based on degree centrality (connectedness) of the seed concept node and surrounding nodes; they are also based on frequency of occurrence measures of the edges between the seed concept and surrounding nodes as well as between the nodes surrounding the seed concept and the neighbors of those nodes. A PubMed query log is used for training and testing models for interestingness. This log contains a set of user searches over a 24-hour period, and we make the assumption that co-occurrence of concepts with the seed concept in searches demonstrates interestingness of that concept with regard to the seed concept. Graph generation begins by the selection of a set of all predications containing the seed concept from the Semantic Medline database (our training dataset uses Alzheimer\u27s disease as the seed concept). The graph is built with the seed concept as the central node. Additional nodes are added for each concept that occurs with the seed concept in the initial predications and an edge is created for each instance of a predication containing the two concepts. The edges are labeled with the specific predicate in the predication. This graph is extended to include additional nodes within two leaps from the seed concept. The concepts in the PubMed query logs are normalized to UMLS concepts or Entrez Gene symbols using MetaMap. Token-based and user-based counts are collected for each co-occurring term. These measures are combined to create a weighted score which is used to determine three potential thresholds of interestingness based on deviation from the mean score. The concepts that are included in both the graph and the normalized log data are identified for use in model training and testing

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein--protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence ``Protein A causes protein B to bind protein C&#39;&#39; can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP&#39;09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing.&nbsp; Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP&#39;09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP&#39;11 and BioNLP&#39;13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.</p

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein-protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence “Protein A causes protein B to bind protein C” can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP'09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing. Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP'09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP'11 and BioNLP'13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.Siirretty Doriast

Structuring the Unstructured: Unlocking pharmacokinetic data from journals with Natural Language Processing

The development of a new drug is an increasingly expensive and inefficient process. Many drug candidates are discarded due to pharmacokinetic (PK) complications detected at clinical phases. It is critical to accurately estimate the PK parameters of new drugs before being tested in humans since they will determine their efficacy and safety outcomes. Preclinical predictions of PK parameters are largely based on prior knowledge from other compounds, but much of this potentially valuable data is currently locked in the format of scientific papers. With an ever-increasing amount of scientific literature, automated systems are essential to exploit this resource efficiently. Developing text mining systems that can structure PK literature is critical to improving the drug development pipeline. This thesis studied the development and application of text mining resources to accelerate the curation of PK databases. Specifically, the development of novel corpora and suitable natural language processing architectures in the PK domain were addressed. The work presented focused on machine learning approaches that can model the high diversity of PK studies, parameter mentions, numerical measurements, units, and contextual information reported across the literature. Additionally, architectures and training approaches that could efficiently deal with the scarcity of annotated examples were explored. The chapters of this thesis tackle the development of suitable models and corpora to (1) retrieve PK documents, (2) recognise PK parameter mentions, (3) link PK entities to a knowledge base and (4) extract relations between parameter mentions, estimated measurements, units and other contextual information. Finally, the last chapter of this thesis studied the feasibility of the whole extraction pipeline to accelerate tasks in drug development research. The results from this thesis exhibited the potential of text mining approaches to automatically generate PK databases that can aid researchers in the field and ultimately accelerate the drug development pipeline. Additionally, the thesis presented contributions to biomedical natural language processing by developing suitable architectures and corpora for multiple tasks, tackling novel entities and relations within the PK domain