Semantic annotation in biomedicine: the current landscape

Better use of electronic medical record (EMR) in clinical practice

Electronic medical records (EMRs) are considered valuable source of clinical information, ensuring effective and reliable information exchange among physicians and departments participating in patient care, and supporting clinical decision making. However, EMRs largely consist of unstructured, free-form textual content that require manual curation and analysis performed by domain experts. A recent study examining the allocation of physician time in ambulatory practice [2] confirmed the findings of previous similar studies (e.g. [3]), namely that physicians spend almost twice as much time on the management of EMRs and related desk work than on direct clinical face time with patients. Considering the inefficiency of manual curation of EMRs, automation of the process is required if the potentials of EMRs are to be exploited in clinical practice [4].

Semantic annotators provide the grounds for the required automation by extracting clinical terms from free-form text of EMRs, and disambiguating the extracted terms with concepts of a structured vocabulary, such as UMLS Metathesaurus. The identified concepts can be subsequently used to search a repository of biomedical literature or evidence-based clinical resources, in order to enrich EMRs with information pertinent to the patient’s state. The extracted terms can also be used for making summaries of clinical notes and articles [5].

Improved search and retrieval of resources for biomedical research

Publicly available biomedical data, tools, services, models and computational workflows continuously increase in number, size and complexity. While this ever-growing abundance of valuable resources opens up unprecedented opportunities for biomedical research, it is also making it ever more challenging for researchers to efficiently discover and use the resources required for accomplishing their tasks [6]. Hence, automation of the search and discovery processes has turned into a necessity.

Clinical information stored in EMRs is also important in medical research, e.g., for comparative effectiveness research, and epidemiological and clinical research studies [7]. Considering the unstructured nature of EMRs and their abundance, automated document classification and information extraction methods are essential for assuring the efficiency and effectiveness of search and retrieval of relevant information from large EMR collections. Semantic annotation techniques can play a significant role in this regard. For instance, they can be used to extract domain-specific concepts that could serve as discriminative features for building automated classifiers of clinical documents [8]. Based on such classification, clinical documents can be searched more effectively [7]. Furthermore, semantic concepts extracted from biomedical literature can also be used for semantic indexing and retrieval of biomedical publications [9] or biomedical tools and services [6]. In particular, biomedical Information Retrieval systems use semantic annotators to expand the users’ queries with concepts and terms from vocabularies/ontologies (mapping the query text to the appropriate ontology concepts, and then expanding the query with the terms associated with the mapped concepts), as well as to classify the retrieved documents based on their content or the occurrence of specific topics in the documents [1].

Disambiguation of abbreviations

Polysemous abbreviations are frequently present in biomedical literature and clinical texts making it difficult for researchers and clinical practitioners to understand texts that are outside the strict area of their expertise [10]. According to Chang et al. [11], in biomedical journal articles, abbreviations with six or less characters have on average 4.61 possible meanings. For instance, “ANA” has numerous possible meanings among which the most frequent ones are “antinuclear antibodies”, “American Nurses Association”, “Alko Non-Alcohol”, and “anandamide”.

Semantic annotators combined with general-purpose, machine-readable knowledge bases, such as DBpedia (Table 1), can be used to disambiguate polysemous abbreviations and unambiguously describe abbreviated terms based on the context in which they appear [10]. This can help researchers and practitioners better understand the meaning of such abbreviations.

Seamless integration of data from disparate sources

Biomedical data are stored and maintained in disparate repositories. For instance, according to the 2016 Molecular Biology Database Update, there are 1685 biological databases [12]. This complicates the tasks of data management, retrieval and exploitation since one needs to, first, locate the repositories that contain the required data; then, to familiarize oneself with the meaning of the attributes and data types used in each repository; and, finally, learn how to access and query the repositories [13].

For this reason, data integration can be highly useful for medical researchers. Jonquet et al. [14] have nicely illustrated the need for seamless integration of data from various medical sources: “a researcher studying the allelic variations in a gene would want to know all the pathways that are affected by that gene, the drugs whose effects could be modulated by the allelic variations in the gene, and any disease that could be caused by the gene, and the clinical trials that have studied drugs or diseases related to that gene. The knowledge needed to address such questions is available in public biomedical resources; the problem is finding [and connecting] that information.”

Ontologies that are used to semantically annotate items in biomedical repositories allow for weaving semantic links both within and across repositories thus establishing a semantic network of biomedical items [13]. If both ontologies and resources they connect (through semantic annotations) are in public domain, the resulting network takes the form of Linked Open Data, as has already been shown in the Linked Life Data initiative (Table 1).

Table 2 provides a more structured view of some application cases for biomedical semantic annotation technology.

Semantic biomedical annotation tools

Tables 3 and 4 gives an overview of the semantic annotation tools that fulfilled the above given criteria and thus were selected for inclusion in our study.¹ The table compares the selected tools with respect to several characteristic, including those related to the underlying annotation method (configurability and disambiguation), the vocabulary (terminology) the tool relies on, the tool’s speed,² its implementation aspects, and availability. The table also points to some of the tools’ specific features, which are further examined in the tool descriptions given below.

As shown in Tables 3 and 4 and further discussed below, all the tools are configurable in several and often different ways, making it very difficult, if possible at all, to give a fair general comparison of the tools. In other words, we believe that the only way to properly compare these (and similar) annotation tools is in the context of a specific application case, where each tool would be configured based on the application requirements. We expand on this in “Application-specific tool benchmarking” section where we discuss the need for a benchmarking toolkit that would facilitate this kind of application-specific tool benchmarking. Still, to offer some general insight into the annotation capabilities of the selected tools, in “Summary of benchmarking results” section we briefly report on the benchmarking studies that included several of the examined semantic annotators. In the following, we introduce the selected semantic annotation tools and discuss their significant features. The tools are presented in the order that corresponds to their order in Tables 3 and 4.

Clinical Text Analysis and Knowledge Extraction System (cTAKES) [4] is a well-known toolkit for semantic annotation of biomedical documents in general, and clinical research texts in particular. It is built on top of two well-established and widely used open-source NLP frameworks: Unstructured Information Management Architecture - UIMA [28] and OpenNLP [29]. cTAKES is developed in a modular manner, as a pipeline consisting of several text processing components that rely on either rule-based or ML techniques. Recognition of concept mentions and annotation with the corresponding concept identifiers is done by a component that implements a dictionary look-up algorithm. For building the dictionary, cTAKES relies on UMLS. The concept recognition component does not resolve ambiguities that result from identifying multiple concepts for the same text span. Disambiguation is enabled through the integration of YTEX [7] in the cTAKES framework and its pipelines. YTEX is a knowledge-based word sense disambiguation component that relies on the knowledge encoded in UMLS. In particular, YTEX implements an adaptation of the Lesk method [30], which scores candidate concepts for an ambiguous term by summing the semantic relatedness between each candidate concept and the concepts in its context window.

NOBLE Coder [20] is another open-source, general-purpose biomedical annotator. It can be configured to work with arbitrary vocabularies. Besides enabling users to annotate documents with existing vocabularies (terminologies), NOBLE Coder also provides them with a Graphical User Interface where they can create custom terminologies by selecting one or more branches from a set of existing vocabularies, and/or filtering vocabularies by semantic types. It also allows for the dynamic change of the terminology (adding new concepts, removing existing ones) while processing. The flexibility of this annotator also lies in the variety of supported concept matching strategies, aimed at meeting the needs of different kinds of NLP tasks. For example, the ‘best match’ strategy aims at high precision, and thus returns few candidates (at most); as such, it is suitable for concept coding and information extraction NLP tasks. The supported matching strategies allow for annotation of terms consisting of single words, multiple words, and abbreviations. Thanks to its greedy algorithm, NOBLE Coder can efficiently process large textual corpora. To disambiguate terms with more than one associated concept, this tool relies on a set of simple heuristic rules such as giving preference to candidates that map to a larger number of source vocabularies, or candidates where the term is matched in its ‘original’ form, i.e., without being stemmed or lemmatized.

MetaMap [31] is probably the most well-known and most widely used biomedical annotator. It was developed by the U.S. National Library of Medicine. It maps biomedical entity mentions of the input text to the corresponding concepts in the UMLS Metathesaurus. Each annotation includes a score that reflects how well the concept matches the biomedical term/phrase from the input text. The annotation process can be adapted in several ways by configuring various elements of the annotation process such as the vocabulary used, the syntactic filters applied to the input text, and the matching between text and concepts, to name a few. Besides the flexibility enabled by these configuration options, another strong aspect of MetaMap is its thorough and linguistically principled approach to the lexical and syntactic analyses of input text. However, this thoroughness is also the cause of one of MetaMap’s main weaknesses, namely its long processing time, and thus its inadequacy for annotating large corpora. Another weakness lies in its disambiguation approach which is not able to effectively deal with ambiguous terms [32]. In particular, for disambiguation of terms, MetaMap combines two approaches: i) removal of word senses deemed problematic for (literature-centric) NLP usage, based on a manual study of UMLS ambiguity, and ii) a word sense disambiguation algorithm that chooses a concept with the most likely semantic type for a given context [33].

NCBO annotator [14] is provided by the U.S. National Center for Biomedical Ontology (NCBO) as a freely available Web service. It is based on a two-stage annotation process. The first stage relies on a concept recognition tool that uses a dictionary to identify mentions of biomedical concepts in the input text. In particular, NCBO annotator makes use of the MGrep tool [34], which was chosen over MetaMap due to its better performance along several examined dimensions [35]. The dictionary for this annotation stage is built by pulling concept names and descriptions from biomedical ontologies and/or thesauri relevant for the domain of the corpus to be annotated (typically UMLS Metathesaurus and BioPortal ontologies, Table 1). In the second stage, the initial set of concepts, referred to as direct annotations, is extended using the structure and semantics of relevant biomedical ontologies. For instance, semantic distance measures are used to extend the direct annotations with semantically related concepts; the computation of semantic distance is configurable, and can be based, for instance, on the distance between the concepts in the ontology graph. Semantic relations between concepts from different ontologies, established through ontology mappings, serve as another source for finding semantically related concepts that can be used to extend the scope of direct annotations. The NCBO annotator is unique in its approach to associate concept mentions with multiple concepts, instead of finding one concept that would be the best match for the given context.

BioMedical Concept Annotation System ( BeCAS ) [36] is a Web-based tool for semantic annotation of biomedical texts, primarily biomedical research papers. Besides being available through a Web-based user interface, it can be programmatically accessed through a Web-based (RESTful) Application Programing Interface (API), and a widget, easily embeddable in Web pages. Like majority of the aforementioned annotation tools, BeCAS is an open-source modular system, comprising of several modules for text preprocessing including, e.g., sentence splitting, tokenization, lemmatization, among others, as well as modules for concept detection and abbreviation resolution. Most of the concept detection modules in BeCAS apply a term-to-concept matching approach to identify and annotate mentions of several types of biomedical entities, including species, enzymes, chemicals, drugs, diseases, etc. This approach relies on a custom dictionary, i.e., a database of concepts and associated terms, compiled by pulling concepts from various meta-thesauri and ontologies such as UMLS Metathesaurus, NCBI BioSystems database, ChEBI, and the Gene Ontology (Table 1). For the identification of gene and protein mentions and their disambiguation with appropriate concepts, BeCAS makes use of Gimli, an open source tool that implements Conditional Random Fields (CRF) for named entity recognition in biomedical texts [37] (see Entity-specific biomedical annotation tools section).

Whatizit is a freely available Web service for annotation of biomedical texts with concepts from several ontologies and structured vocabularies [38]. Like previously described tools, it is also developed in a modular way so that different components can be combined into custom annotation pipelines, depending on the main theme of the text being processed. For example, whatizitGO is a pipeline for identifying Gene Ontology (GO) concepts in the input text, while whatizitOrganism identifies species defined in the NCBI taxonomy. In Whatizit, concept names are transformed into regular expressions to account for morphological variability in the input texts [39]. Such regular expressions are then compiled into Finite State Automata, which assure quick processing regardless of the length of the text and the size of the used vocabulary; therefore, processing time is linear with respect to the length of the text. Whatizit also offers pipelines that allow for the recognition of biomedical entities of a specific type based on two or more knowledge sources. For instance, whatizitSwissprotGo is the pipeline for the annotation of protein mentions based on the UniProtKb/Swiss-Prot knowledge base (Table 1) and the Gene Ontology. Finally, there are more complex pipelines that combine simpler pipelines to enable detection and annotation of two or more types of biomedical entities. For instance, whatizitEbiMed incorporates whatizitSwissprotGo, whatizitDrug and whatizitOrganism to allow for the detection and annotation of proteins, drugs and species.

ConceptMapper [21] is a general purpose dictionary lookup tool, developed as a component of the open-source UIMA NLP framework. Unlike the other annotators that have been examined so far, ConceptMapper is the only one that was not specifically developed for the biomedical domain, but is rather generic and configurable-enough to be applicable to any domain. Its flexibility primarily stems from the variety of options for configuring its algorithm for mapping dictionary entries onto input text. For instance, it can be configured to detect entity mentions even when they appear in the text as disjoint multi-word phrases, e.g., in the text “intraductal and invasive mammary carcinoma”, it would recognize “intraductal carcinoma” and “invasive carcinoma” as diagnosis. It can also deal with a variety of ways a concept can be mentioned in the input text, e.g., synonyms and different word forms. This is enabled by a dictionary that for each entry stores several possible variants, and connects them to the same concept. For instance, the entry with the main (canonical) form “spine” would also include variants such as “spinal”, “spinal column”, “vertebral column”, “backbone”, and others, and associates them all with the semantic type AnatomicalSite. Even though ConceptMapper is not originally targeted at the biomedical domain, if properly configured, it can even outperform state-of-the-art biomedical annotators [24]. However, the task of determining the optimal configuration and developing a custom dictionary might be overwhelming for regular users; we return to this topic in “Adaptation to new document type(s) and/or terminologies specific to particular biomedical subdomain” section.

Neji [40] is yet another open source and freely available software framework for annotation of biomedical texts. Its high modularity is achieved by having each text processing task wrapped in an independent module. These modules can be combined in different ways to form different kinds of text processing and annotation pipelines, depending on the requirements of specific annotation tasks. The distinct feature of Neji is its capacity for multi-threaded data processing, which assures high speed of the annotation process. Neji makes use of existing software tools and libraries for text processing, e.g., tokenization, sentence splitting, lemmatization, with some adjustments to meet the lexical specificities of biomedical texts. For concept recognition, Neji supports both dictionary-lookup matching and ML-based approaches by customizing existing libraries that implement these approaches. For instance, like BeCAS, it uses the CRF tagger implemented in Gimli. Hence, various CRF models trained for Gimli can be used in Neji, each model targeting a specific type of biomedical entities such as genes or proteins. Since Gimli does not perform disambiguation, Neji has introduced a simple algorithm to associate each recognized entity mention with a unique biomedical concept.

Summary of benchmarking results

Tseytlin et al. [20] have conducted a comprehensive empirical study that includes five state-of-the-art semantic annotators that were compared based on the execution time and standard annotation performance metrics (precision, recall, F1-measure). Four of the benchmarked tools, namely cTAKES, MetaMap,³ ConceptMapper, and NOBLE Coder have been directly covered in the previous section, whereas the fifth tool - MGrep - was considered as a service used by NCBO Annotator in the first stage of its annotation process. The benchmarking was done on two publicly available, human-annotated corpora (see Table 5): one (ShARe) consisting of annotated clinical notes, the other (CRAFT) of annotated biomedical literature. Documents from the former corpus (ShARe) were annotated using the SNOMED-CT vocabulary (Table 1), while for the annotation of the latter corpus (CRAFT), a subset of OBO ontologies were used as recommended by the corpus developers.

The study showed that all the tools performed better on the clinical notes corpus (ShARe) than on the corpus of biomedical literature (CRAFT). The results demonstrated that on the ShARe corpus, NOBLE Coder, cTAKES, MGrep, and MetaMap were of comparable performance, while only ConceptMapper somewhat lagged behind. On the CRAFT corpus, NOBLE Coder, cTAKES, MetaMap, and ConceptMapper were quite aligned, whereas MGrep performed significantly worse, due to very low recall. In terms of speed, on both corpora, ConceptMapper proved to be the fastest one. It was followed by cTAKES, NOBLE Coder, and MGrep, respectively, whose speed was more-or-less comparable. However, MetaMap was by far the slowest (about 30 times slower than the best performing tool).

Another comprehensive empirical study that compared several semantic annotators with respect to their speed and the quality of the produced annotations is reported in [40]. The study included five contemporary annotators - Whatizit, MetaMap, Neji, Cocoa, and BANNER, which were compared on three manually annotated corpora of biomedical publications, namely NCBI Disease corpus, CRAFT, and AnEM (see Table 5). Evaluation on the CRAFT corpus considered 6 different biomedical entity types (e.g. species, cell, cellular component, gene and proteins), while on the other two corpora only the most generic type was considered, i.e., anatomical entity for AnEM, and disorder for NCBI. Two of the benchmarked annotators are either no longer available (Cocoa) or no longer maintained (BANNER⁴), whereas the other three were covered in the previous section. Benchmarking was done for each considered type of biomedical concept separately, and also using different configurations of the examined tools (e.g., five different term-to-concept matching techniques were examined).

The study showed that the tools’ performance varied considerably between various configuration options, in particular, various strategies for recognizing entity mentions in the input text. This variability in the performance associated with different configurations was also confirmed by Funk et al. [24]; we return to this topic in “Application-specific tool benchmarking” section.

Overall, Neji had the best results, especially on the CRAFT corpus, with significant improvements over the other tools on most of the examined concept types. Whatizit proved to have the most consistent performance across different configuration options, with an average variation of 4% in F1-measure. In terms of speed, Neji significantly outpaced the other tools.

The lack of sufficient context for understanding entity mentions

An often cited source of difficulty associated with the recognition of entities in biomedical texts is the lack of sufficient context for interpreting the entity mentions [59]. For instance, Tseytlin et al. [20] reported that the largest proportion of annotation errors made by their NOBLE Coder annotator was due to the missing or incomplete context or background knowledge.

The collective annotation approach was proposed as a way of dealing with this challenge [59]. It relies on the global topical coherence of entities mentioned in a piece of text and is done by disambiguating a set of related mentions simultaneously. The basic idea is that if multiple entity mentions co-occur in the same sentence or paragraph, they can be considered semantically related. In particular, the approach proposed by Zheng et al. [59] consists of creating a document graph (G _d ) with entity mentions recognized in a document as nodes, while edges are established between those pairs of nodes (entity mentions) that co-occur in the same sentence or paragraph of the document. Each entity mention is then connected with one or more entity candidates from the knowledge base (KB) based on the name variants associated with entities in the KB. Finally, for each entity mention (m) - entity candidate (c) pair (m,c), a score is computed based on i) the general popularity of the candidate entity c in the KB, that is, its level of connectedness to other entities in the KB (non-collective score), and ii) level of connectedness of candidate c only with candidate concepts of entity mentions that are connected to mention m in the G _d graph. The candidate entity c from the (m,c) pair with the highest score is selected as the appropriate entity for the given entity mention m. A similar approach was proposed and proved effective for general purpose semantic annotators in work such as [60].

Scaling to very large document sets

One of the weaknesses of today’s biomedical semantic annotators lies in their speed, that is, the time required for completing the annotation task on very large corpora (with tens and hundreds of millions of documents) [20]. Note that speed estimates given in Tables 3 and 4 (qualifying almost all examined tools as suitable for real-time processing) are based on the experimental results reported in the literature, where experiments were done with small corpora (up to 200 documents).

Divita et al. [61] aimed at using semantic annotation to improve information extraction and retrieval of clinical notes from the Veterans Informatics and Computing Infrastructure (VINCI) hosting huge and continuously growing amounts of medical notes. However, they found today’s annotators unapt for that task, as, based on the Divita et al., even when running on several multi-core machines, today’s annotators would need multiple years to index VINCI notes with semantic concepts. As a solution to this challenge, they proposed Sophia, an UMLS-based annotation tool, that deals with high throughput by replicating either certain components of the annotation pipeline or the entire pipeline [61]. Sophia is built from the components of the v3NLP framework [62], a suite of middleware text-processing components aimed for building various kinds of NLP applications. In particular, Sophia makes use of the v3NLP components for dealing with the idiosyncrasies of clinical texts, as well as the framework’s scaling-up and scaling-out functionalities for efficiently handling huge quantities of texts.

Adaptation to new document type(s) and/or terminologies specific to particular biomedical subdomain

Another challenge originates in the variety of biomedical texts and differences among different kinds of text, particularly differences between biomedical literature and clinical text [20, 25]. According to Garla and Brandt [7], “clinical text is often composed of semi-grammatical ‘telegraphic’ phrases, uses a narrower vocabulary than biomedical literature, and is rife with domain-specific acronyms.” In addition, common to both clinical texts and scientific papers is the presence of local dialects, such as specific jargon developed within a medical center, or particular, idiosyncratic protein nomenclatures created within research laboratories [63]. Due to these issues, an annotation tool developed and/or configured for a particular type of medical texts or even one application case, tied to a particular medical institution/center, cannot be directly ported to some other text type and/or application case without, often significant, drop in performance.

A potential solution to this diversity in text types and terminologies is the use of flexible general-purpose annotation tools that can be configured to work with different text types and vocabularies [19]. In fact, Funk et al. [24] have demonstrated that if properly tuned, a generic annotation tool can offer better performance than tools designed specifically for particular biomedical task or domain. The key is in the modularity and flexibility of a tool so that one can precisely control how terms in the text are to be matched against the available terminologies.

While the majority of the annotators listed in Tables 3 and 4 were developed to be modular and flexible, their configuration is a complex task for users lacking expertise in NLP and not knowing the intricacies of the tool’s internal functioning. The latter is especially relevant as not all parameters equally affect the performance; also, the interaction of the parameters need to be considered.

Besides configuring the tool’s annotation method, e.g., kinds of text processing and term matching options, adaptation to a different biomedical (sub)domain also requires either development or, at least, customization of the dictionary that the tool uses to recognize concept mentions in the input text. While there are numerous ontologies, knowledge bases, thesauri, and similar kinds of biomedical resources that can be used for dictionary development, that task is often overly complex for regular users. This is because each tool has its own idiosyncratic structure and format for vocabulary representation and storage, designed to optimally match the tool’s annotation algorithm. To alleviate the task of dictionary development/customization, Tseytlin et al. [20] have developed an interactive terminology building tool, as a component of the NOBLE Coder annotator. The tool allows users to import existing terminologies (of various kinds), and then customize them by selecting only certain segments (branches) of the imported terminologies, and/or to filter them by semantic types. A tool of this type would be a useful complement to any semantic annotator that relies on a dictionary-lookup approach.

Application-specific tool benchmarking

As argued in “Semantic Biomedical Annotation Tools” section, benchmarking of semantic annotators requires that each annotator is configured based on the specificities of the benchmarking task, so that it demonstrates its optimal performance on the task. The effect of configuration on the annotators’ performance was well demonstrated by Funk et al. [24] in their comprehensive empirical study that included MetaMap, ConceptMapper, and NCBO Annotator (see Semantic Biomedical Annotation Tools section). The researchers examined over 1000 parameter combinations in the context of the CRAFT evaluation corpus (Table 5) and 8 different terminologies (ontologies). They found that default parameter values often do not lead to the best performance, and that by appropriately setting parameters, F-measure can be significantly increased (even by 0.4 points). This suggests that if it is to be used for making a decision on the annotator to adopt in a particular application case, the benchmarking studies should not be based on the tools’ default configuration, but should include tools customized to the specific features of the application case.

Another requirement for application-specific benchmark study is the selection of appropriate evaluation corpora and terminology source for building or customizing the tools’ dictionaries. While numerous annotated corpora have been developed (Table 5), including both manually annotated gold standard corpora and corpora annotated in an automated or semi-automated way known as silver standards, the information about these resources are dispersed on the web and it takes time and effort to collect information about the available evaluation corpora and their features.

Considering the above stated difficulties associated with the setup of application-specific benchmarking studies, we point to the need for a benchmarking ‘toolkit’ that would facilitate the task of tool benchmarking in the context of a specific application case. An important component of such a toolkit would be a searchable registry of existing annotated corpora. For each corpus, the registry should include basic qualitative and quantitative information, e.g., the sources and types of documents that it includes, and the vocabularies or ontologies that were used for annotating the corpus, among others. In addition, the registry of annotated corpora would need to contain guidelines for how each corpus should be used, references to the studies where the corpus was previously used, and any additional information that might be of relevance for effective use of the given corpus.

Another important component of the benchmarking toolkit would be guidelines and/or tools for optimal configuration of annotation tools. The starting point for such guidelines could be the set of suggestions that Funk et al. [24] derived from their study, related to the selection of optimal parameter values based on the terminology (ontology) to be used for annotation. Tools enabling semi-automated or automated parameter tuning would greatly facilitate this task. Algorithmic procedures and tools developed for general purpose semantic annotators, like the one proposed in [64], could be adapted to tune parameters of biomedical annotators.

With such a benchmarking toolkit, it would be also possible to evaluate the performance of general purpose biomedical annotators on the tasks of recognizing and normalizing specific types of biomedical entities, e.g., chemicals, genes, drugs, or diseases. This would allow for evidence-based recommendation of appropriate semantic annotators for entity-specific tasks. While some initial work in this direction has been done by Campos et al. [40] (see Summary of benchmarking results section), only a small number of the current tools have been examined (some of the tools evaluated in their study are no longer available), and they were not tuned to the entity specific annotation tasks. Henceforth, new studies with current general purpose annotators, customized for the entity-specific task at hand, are needed in order to obtain conclusive evidence on the performance of the current tools for specific biomedical entity types.

Semantic annotation in languages other than English

Large majority of tools, ontologies, and corpora developed for biomedical semantic annotation, and biomedical NLP in general, are for the English language. Semantic annotators discussed in the previous sections fall in this category of “English-only” tools. However, the development of NLP resources and tools for semantic annotation in languages other than English has started receiving increasing attention both in research and practice.

The CLEF (Conference and Labs of the Evaluation Forum) conference series have been hosting eHealth Labs where one of the tasks has been entity recognition and normalization, i.e., semantic annotation, in languages other than English, primarily French. Systems developed to face this challenge varied greatly [65, 66]. The team with the best performance at the latest eHealth Lab, held in conjunction with CLEF 2016, proposed a system that could be qualified as a general purpose semantic annotator [67]. In particular, to perform the entity recognition task, this system used Peregrine [68], a dictionary-based concept recognition tool, in conjunction with a dictionary consisting of French vocabularies from UMLS supplemented with automatically translated English UMLS terms. Several post-processing steps were implemented to reduce the number of false positives, such as filtering based on precision scores derived from the training data. Entity normalization relied on the <entity_mention, semantic_group, CUI⁵> combinations extracted from the training set.

Another important initiative was the CLEF-ER challenge that took place in 2013 as part of the Mantra project aimed at providing multilingual documents and terminologies for the biomedical domain [69]. For this challenge, Medline and biomedical patent documents were released in five languages: English, German, French, Spanish, and Dutch. Mappings to English documents were provided for all documents that were in a language other than English, though the mappings were not available between all pairs of languages, e.g., between Spanish and German. The organizers also released the CLEF-ER terminology, a multilingual vocabulary with term synonyms in the above mentioned five languages.⁶ The challenge received several submissions dealing with various challenges of multilingual biomedical NLP, including semantic annotation, e.g. [70, 71], and the creation of multilingual corpora, e.g., [72, 73]. An interesting approach to multilingual semantic annotation was proposed by Attardi et al. [71]. The method starts from the English language Silver Standard Corpus (SSC) provided by the CLEF-ER organizers [72], which is first translated into a target language corpus, and then entity annotations are ‘transferred’ to it. The translation is done using an open-source toolkit for statistical phrase-based machine translation. The word alignment information produced by the translation tool is used to determine the correspondence between entities in the source and the target language sentences. The resulting annotated corpus is referred to as the Bronze Standard Corpus (BSC). In addition, a dictionary of entities is also created, which associate each <entity_mention, semantic_group > pair with all the corresponding CUIs that appeared in the SSC. The BSC is used to train a Named Entity detection model, which is aimed at associating entity mentions with their semantic groups. This model is then used for tagging entity mentions in the target language sentences with the proper semantic group. Finally, after entity mentions have been assigned to their semantic group, each mention is linked to corresponding CUIs by looking up CUIs associated with the <entity_mention, semantic_group > pairs in the previously built dictionary.