Gene Mention Research Articles

The Markyt visualisation, prediction and benchmark platform for chemical and gene entity recognition at BioCreative/CHEMDNER challenge.

Biomedical text mining methods and technologies have improved significantly in the last decade. Considerable efforts have been invested in understanding the main challenges of biomedical literature retrieval and extraction and proposing solutions to problems of practical interest. Most notably, community-oriented initiatives such as the BioCreative challenge have enabled controlled environments for the comparison of automatic systems while pursuing practical biomedical tasks. Under this scenario, the present work describes the Markyt Web-based document curation platform, which has been implemented to support the visualisation, prediction and benchmark of chemical and gene mention annotations at BioCreative/CHEMDNER challenge. Creating this platform is an important step for the systematic and public evaluation of automatic prediction systems and the reusability of the knowledge compiled for the challenge. Markyt was not only critical to support the manual annotation and annotation revision process but also facilitated the comparative visualisation of automated results against the manually generated Gold Standard annotations and comparative assessment of generated results. We expect that future biomedical text mining challenges and the text mining community may benefit from the Markyt platform to better explore and interpret annotations and improve automatic system predictions.Database URL: http://www.markyt.org, https://github.com/sing-group/Markyt

NTTMUNSW BioC modules for recognizing and normalizing species and gene/protein mentions

In recent years, the number of published biomedical articles has increased as researchers have focused on biological domains to investigate the functions of biological objects, such as genes and proteins. However, the ambiguous nature of genes and their products have rendered the literature more complex for readers and curators of molecular interaction databases. To address this challenge, a normalization technique that can link variants of biological objects to a single, standardized form was applied. In this work, we developed a species normalization module, which recognizes species names and normalizes them to NCBI Taxonomy IDs. Unlike most previous work, which ignored the prefix of a gene name that represents an abbreviation of the species name to which the gene belongs, the recognition results of our module include the prefixed species. The developed species normalization module achieved an overall F-score of 0.954 on an instance-level species normalization corpus. For gene normalization, two separate modules were respectively employed to recognize gene mentions and normalize those mentions to their Entrez Gene IDs by utilizing a multistage normalization algorithm developed for processing full-text articles. All of the developed modules are BioC-compatible .NET framework libraries and are publicly available from the NuGet gallery.Database URL: https://sites.google.com/site/hjdairesearch/Projects/isn-corpus

PGenN, a gene normalization tool for plant genes and proteins in scientific literature.

BackgroundAutomatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines.MethodsIn this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases.ResultsWe evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/).

Curatable Named-Entity Recognition Using Semantic Relations.

Named-entity recognition (NER) plays an important role in the development of biomedical databases. However, the existing NER tools produce multifarious named-entities which may result in both curatable and non-curatable markers. To facilitate biocuration with a straightforward approach, classifying curatable named-entities is helpful with regard to accelerating the biocuration workflow. Co-occurrence Interaction Nexus with Named-entity Recognition (CoINNER) is a web-based tool that allows users to identify genes, chemicals, diseases, and action term mentions in the Comparative Toxicogenomic Database (CTD). To further discover interactions, CoINNER uses multiple advanced algorithms to recognize the mentions in the BioCreative IV CTD Track. CoINNER is developed based on a prototype system that annotated gene, chemical, and disease mentions in PubMed abstracts at BioCreative 2012 Track I (literature triage). We extended our previous system in developing CoINNER. The pre-tagging results of CoINNER were developed based on the state-of-the-art named entity recognition tools in BioCreative III. Next, a method based on conditional random fields (CRFs) is proposed to predict chemical and disease mentions in the articles. Finally, action term mentions were collected by latent Dirichlet allocation (LDA). At the BioCreative IV CTD Track, the best F-measures reached for gene/protein, chemical/drug and disease NER were 54 percent while CoINNER achieved a 61.5 percent F-measure. System URL: http://ikmbio.csie.ncku.edu.tw/coinner/ introduction.htm.

Incorporating domain knowledge in chemical and biomedical named entity recognition with word representations.

BackgroundChemical and biomedical Named Entity Recognition (NER) is an essential prerequisite task before effective text mining can begin for biochemical-text data. Exploiting unlabeled text data to leverage system performance has been an active and challenging research topic in text mining due to the recent growth in the amount of biomedical literature.We present a semi-supervised learning method that efficiently exploits unlabeled data in order to incorporate domain knowledge into a named entity recognition model and to leverage system performance. The proposed method includes Natural Language Processing (NLP) tasks for text preprocessing, learning word representation features from a large amount of text data for feature extraction, and conditional random fields for token classification. Other than the free text in the domain, the proposed method does not rely on any lexicon nor any dictionary in order to keep the system applicable to other NER tasks in bio-text data.ResultsWe extended BANNER, a biomedical NER system, with the proposed method. This yields an integrated system that can be applied to chemical and drug NER or biomedical NER. We call our branch of the BANNER system BANNER-CHEMDNER, which is scalable over millions of documents, processing about 530 documents per minute, is configurable via XML, and can be plugged into other systems by using the BANNER Unstructured Information Management Architecture (UIMA) interface.BANNER-CHEMDNER achieved an 85.68% and an 86.47% F-measure on the testing sets of CHEMDNER Chemical Entity Mention (CEM) and Chemical Document Indexing (CDI) subtasks, respectively, and achieved an 87.04% F-measure on the official testing set of the BioCreative II gene mention task, showing remarkable performance in both chemical and biomedical NER. BANNER-CHEMDNER system is available at: https://bitbucket.org/tsendeemts/banner-chemdner.

Improving protein-protein interaction article classification using biological domain knowledge.

Interaction Article Classification (IAC) is a specific text classification application in biological domain that tries to find out which articles describe Protein-Protein Interactions (PPIs) to help extract PPIs from biological literature more efficiently. However, the existing text representation and feature weighting schemes commonly used for text classification are not well suited for IAC. We capture and utilise biological domain knowledge, i.e. gene mentions also known as protein or gene names in the articles, to address the problem. We put forward a new gene mention order-based approach that highlights the important role of gene mentions to represent the texts. Furthermore, we also incorporate the information concerning gene mentions into a novel feature weighting scheme called Gene Mention-based Term Frequency (GMTF). By conducting experiments, we show that using the proposed representation and weighting schemes, our Interaction Article Classifier (IACer) performs better than other leading systems for the moment.

GNormPlus: An Integrative Approach for Tagging Genes, Gene Families, and Protein Domains.

The automatic recognition of gene names and their associated database identifiers from biomedical text has been widely studied in recent years, as these tasks play an important role in many downstream text-mining applications. Despite significant previous research, only a small number of tools are publicly available and these tools are typically restricted to detecting only mention level gene names or only document level gene identifiers. In this work, we report GNormPlus: an end-to-end and open source system that handles both gene mention and identifier detection. We created a new corpus of 694 PubMed articles to support our development of GNormPlus, containing manual annotations for not only gene names and their identifiers, but also closely related concepts useful for gene name disambiguation, such as gene families and protein domains. GNormPlus integrates several advanced text-mining techniques, including SimConcept for resolving composite gene names. As a result, GNormPlus compares favorably to other state-of-the-art methods when evaluated on two widely used public benchmarking datasets, achieving 86.7% F1-score on the BioCreative II Gene Normalization task dataset and 50.1% F1-score on the BioCreative III Gene Normalization task dataset. The GNormPlus source code and its annotated corpus are freely available, and the results of applying GNormPlus to the entire PubMed are freely accessible through our web-based tool PubTator.

Breast cancer in male veteran population: an analysis from VA cancer registry.

Male breast cancer is rare and makes up < 1% of all cases of breast cancers. Treatment and survival stage per stage is mainly based on what is known from female breast cancer. We determined the pathological features, stage, treatment of breast cancer in male veterans and their survival outcome. Medical records of male patients diagnosed with breast cancer at the Veterans Affairs Medical Centers of Washington DC, Baltimore, Maryland, and Martinsburg, West Virginia, from 1992-2012 were reviewed after iInstitutional review board approval. From 1995-2012, 51 male patients with breast cancer were identifed from cancer registry. Of those, 57% were African American, 41% white, and 2% other race. Median age was 68 years (range, 44-86 years). Palpable mass was presenting symptoms in 80%, and gynecomastia or bloody nipple discharge in 16%. Family history of breast cancer in immediate family was positive in 11 patients without mention of BRCA genes except in one who was BRCA2-positve. ER/PR (estrogen-/progesterone-receptor) was positive in 71%, ER-positive/PR-negative in 2%, ER-positive/PR-positive /HER2-positive in 4%, ER-negative/PR-negative /HER2-triple negative in 4%. In all, 41% and 57% had right and left breast cancer, respectively; 80% had mastectomy, 36% had lymph node involvement (1-13 LN), 90% had invasive ductal carcinoma, 8% DCIS, and 2% sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV. Twenty four percent of the patients had combination chemotherapy, and 66% were given tamoxifen. Eight percent had relapsed or recurrent disease within 1-5 years of their diagnosis and died within 2-12 years after the relapse. At median follow-up of 174 months (range, 4 months-19 years), 56% had died, 42% were alive, and 6% had been lost to follow-up. This is a very small retrospective chart review. Further large prospective studies are desired. Median age at diagnosis of breast cancer seems to be higher in men (70 years) than it is in women (60 years). Invasive ductal carcinoma is the main pathology, and 73% of the tumors were ER-positive. The survival rate at more than 10 years of follow-up was about 40%. Stage versus survival revealed no difference in mortality.

Gene Name Disambiguation Using Multi-Scope Species Detection.

Species detection is an important topic in the text mining field. According to the importance of the research topics (e.g., species assignment to genes and document focus species detection), some studies are dedicated to an individual topic. However, no researcher to date has discussed species detection as a general problem. Therefore, we developed a multi-scope species detection model to identify the focus species for different scopes (i.e., gene mention, sentence, paragraph, and global scope of the entire article). Species assignment is one of the bottlenecks of gene name disambiguation. In our evaluation, recognizing the focus species of a gene mention in four different scopes improved the gene name disambiguation. We used the species cue words extracted from articles to estimate the relevance between an article and a species. The relevance score was calculated by our proposed entities frequency-augmented invert species frequency (EF-AISF) formula, which represents the importance of an entity to a species. We also defined a relation guide factor (RGF) to normalize the relevance score. Our method not only achieved better performance than previous methods but also can handle the articles that do not specifically mention a species. In the DECA corpus, we outperformed previous studies and obtained an accuracy of 88.22 percent.

A Multistage Gene Normalization System Integrating Multiple Effective Methods

Gene/protein recognition and normalization is an important preliminary step for many biological text mining tasks. In this paper, we present a multistage gene normalization system which consists of four major subtasks: pre-processing, dictionary matching, ambiguity resolution and filtering. For the first subtask, we apply the gene mention tagger developed in our earlier work, which achieves an F-score of 88.42% on the BioCreative II GM testing set. In the stage of dictionary matching, the exact matching and approximate matching between gene names and the EntrezGene lexicon have been combined. For the ambiguity resolution subtask, we propose a semantic similarity disambiguation method based on Munkres' Assignment Algorithm. At the last step, a filter based on Wikipedia has been built to remove the false positives. Experimental results show that the presented system can achieve an F-score of 90.1%, outperforming most of the state-of-the-art systems.

Collective Instance-Level Gene Normalization on the IGN Corpus

A high proportion of life science researches are gene-oriented, in which scientists aim to investigate the roles that genes play in biological processes, and their involvement in biological mechanisms. As a result, gene names and their related information turn out to be one of the main objects of interest in biomedical literatures. While the capability of recognizing gene mentions has made significant progress, the results of recognition are still insufficient for direct use due to the ambiguity of gene names. Gene normalization (GN) goes beyond the recognition task by linking a gene mention to a database ID. Unlike most previous works, we approach GN on the instance-level and evaluate its overall performance on the recognition and normalization steps in abstracts and full texts. We release the first instance-level gene normalization (IGN) corpus in the BioC format, which includes annotations for the boundaries of all gene mentions and the corresponding IDs for human gene mentions. Species information, along with existing co-reference chains and full name/abbreviation pairs are also provided for each gene mention. Using the released corpus, we have designed a collective instance-level GN approach using not only the contextual information of each individual instance, but also the relations among instances and the inherent characteristics of full-text sections. Our experimental results show that our collective approach can achieve an F-score of 0.743. The proposed approach that exploits section characteristics in full-text articles can improve the F-scores of information lacking sections by up to 1.8%. In addition, using the proposed refinement process improved the F-score of gene mention recognition by 0.125 and that of GN by 0.03. Whereas current experimental results are limited to the human species, we seek to continue updating the annotations of the IGN corpus and observe how the proposed approach can be extended to other species.

GeneRIF indexing: sentence selection based on machine learning.

BackgroundA Gene Reference Into Function (GeneRIF) describes novel functionality of genes. GeneRIFs are available from the National Center for Biotechnology Information (NCBI) Gene database. GeneRIF indexing is performed manually, and the intention of our work is to provide methods to support creating the GeneRIF entries. The creation of GeneRIF entries involves the identification of the genes mentioned in MEDLINE®; citations and the sentences describing a novel function.ResultsWe have compared several learning algorithms and several features extracted or derived from MEDLINE sentences to determine if a sentence should be selected for GeneRIF indexing. Features are derived from the sentences or using mechanisms to augment the information provided by them: assigning a discourse label using a previously trained model, for example. We show that machine learning approaches with specific feature combinations achieve results close to one of the annotators. We have evaluated different feature sets and learning algorithms. In particular, Naïve Bayes achieves better performance with a selection of features similar to one used in related work, which considers the location of the sentence, the discourse of the sentence and the functional terminology in it.ConclusionsThe current performance is at a level similar to human annotation and it shows that machine learning can be used to automate the task of sentence selection for GeneRIF annotation. The current experiments are limited to the human species. We would like to see how the methodology can be extended to other species, specifically the normalization of gene mentions in other species.

Breast cancer in male veterans: A retrospective chart review.

e12531 Background: Male breast cancer (BCA) is rare and makes up &lt; 1% of all of breast cancer cases. Treatment is mainly based on what is known from female BCA and survival is similar between genders. Objectives: To investigate the clinicopathologic characteristics of BCA and overall survival in male veterans. Methods: Medical records of male patients diagnosed with breast cancer at the Veterans Affairs Medical Centers of Washington DC, Baltimore and Martinsburg from 1992-2012 were reviewed after Institutional Review Board approval. Results: From 1995-2012, 51 male patients with BCA were identified from cancer registry. 29/51(57%) were African American (AA), 41% Caucasian (WM), and 2% other race. Median age was 70 years (44-86years). Palpable mass was presenting symptom in 41/51(80%) and 8(16%) had gynecomastia or bloody nipple discharge. Family history of breast cancer was positive in 11 patients without mention of BRCA genes except pt #24 who was BRCA2+. 3 patients were exposed to Agent Orange. ER/PR was positive in 36(71%), ER+/PR- in 1(2%), ER+/PR+/HER2+ in 2(4%), ER-/PR-/HER- in 2(4%). 41% &amp; 57% had right and left BCA, respectively. 40 (80%) underwent mastectomy. 18(36%) had lymph node involvement (1-13 LN). 90% had invasive ductal carcinoma (IDC), 8% DCIS, and 2% sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV. 12(24%) received combination chemotherapy. 33(66%) were given tamoxifen. 4(8%) patients had relapsed/recurrent disease in 1-5 years of their diagnosis and died within 2-12 years after the relapse. At median follow up of 174m (4m-19years), 28(56%) patients died (cause of death not known in all), 21(42%) alive and 3(6%) lost to follow up. Conclusions: Median age at diagnosis of BCA seems to be higher in males (70 years) as compared to historical female age (60 years). IDC is the main pathology and 73% tumors were ER +. Survival rate is approximately 40% at &gt;10years of follow up. Survival by stage revealed no difference.

Integrating Various Resources for Gene Name Normalization

The recognition and normalization of gene mentions in biomedical literature are crucial steps in biomedical text mining. We present a system for extracting gene names from biomedical literature and normalizing them to gene identifiers in databases. The system consists of four major components: gene name recognition, entity mapping, disambiguation and filtering. The first component is a gene name recognizer based on dictionary matching and semi-supervised learning, which utilizes the co-occurrence information of a large amount of unlabeled MEDLINE abstracts to enhance feature representation of gene named entities. In the stage of entity mapping, we combine the strategies of exact match and approximate match to establish linkage between gene names in the context and the EntrezGene database. For the gene names that map to more than one database identifiers, we develop a disambiguation method based on semantic similarity derived from the Gene Ontology and MEDLINE abstracts. To remove the noise produced in the previous steps, we design a filtering method based on the confidence scores in the dictionary used for NER. The system is able to adjust the trade-off between precision and recall based on the result of filtering. It achieves an F-measure of 83% (precision: 82.5% recall: 83.5%) on BioCreative II Gene Normalization (GN) dataset, which is comparable to the current state-of-the-art.

A mutation-centric approach to identifying pharmacogenomic relations in text

ObjectivesTo explore the notion of mutation-centric pharmacogenomic relation extraction and to evaluate our approach against reference pharmacogenomic relations. MethodsFrom a corpus of MEDLINE abstracts relevant to genetic variation, we identify co-occurrences between drug mentions extracted using MetaMap and RxNorm, and genetic variants extracted by EMU. The recall of our approach is evaluated against reference relations curated manually in PharmGKB. We also reviewed a random sample of 180 relations in order to evaluate its precision. ResultsOne crucial aspect of our strategy is the use of biological knowledge for identifying specific genetic variants in text, not simply gene mentions. On the 104 reference abstracts from PharmGKB, the recall of our mutation-centric approach is 33–46%. Applied to 282,000 abstracts from MEDLINE, our approach identifies pharmacogenomic relations in 4534 abstracts, with a precision of 65%. ConclusionsCompared to a relation-centric approach, our mutation-centric approach shows similar recall, but slightly lower precision. We show that both approaches have limited overlap in their results, but are complementary and can be used in combination. Rather than a solution for the automatic curation of pharmacogenomic knowledge, we see these high-throughput approaches as tools to assist biocurators in the identification of pharmacogenomic relations of interest from the published literature. This investigation also identified three challenging aspects of the extraction of pharmacogenomic relations, namely processing full-text articles, sequence validation of DNA variants and resolution of genetic variants to reference databases, such as dbSNP.

SR4GN: a species recognition software tool for gene normalization.

As suggested in recent studies, species recognition and disambiguation is one of the most critical and challenging steps in many downstream text-mining applications such as the gene normalization task and protein-protein interaction extraction. We report SR4GN: an open source tool for species recognition and disambiguation in biomedical text. In addition to the species detection function in existing tools, SR4GN is optimized for the Gene Normalization task. As such it is developed to link detected species with corresponding gene mentions in a document. SR4GN achieves 85.42% in accuracy and compares favorably to the other state-of-the-art techniques in benchmark experiments. Finally, SR4GN is implemented as a standalone software tool, thus making it convenient and robust for use in many text-mining applications. SR4GN can be downloaded at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/SR4GN

A dictionary‐based approach to normalizing gene names in one domain of knowledge from the biomedical literature

PurposeGene term variation is a shortcoming in text‐mining applications based on biomedical literature‐based knowledge discovery. The purpose of this paper is to propose a technique for normalizing gene names in biomedical literature.Design/methodology/approachUnder this proposal, the normalized forms can be characterized as a unique gene symbol, defined as the official symbol or normalized name. The unification method involves five stages: collection of the gene term, using the resources provided by the Entrez Gene database; encoding of gene‐naming terms in a table or binary matrix; design of a parametrized finite‐state graph (P‐FSG); automatic generation of a dictionary; and matching based on dictionary look‐up to transform the gene mentions into the corresponding unified form.FindingsThe findings show that the approach yields a high percentage of recall. Precision is only moderately high, basically due to ambiguity problems between gene‐naming terms and words and abbreviations in general English.Research limitations/implicationsThe major limitation of this study is that biomedical abstracts were analyzed instead of full‐text documents. The number of under‐normalization and over‐normalization errors is reduced considerably by limiting the realm of application to biomedical abstracts in a well‐defined domain.Practical implicationsThe system can be used for practical tasks in biomedical literature mining. Normalized gene terms can be used as input to literature‐based gene clustering algorithms, for identifying hidden gene‐to‐disease, gene‐to‐gene and gene‐to‐literature relationships.Originality/valueFew systems for gene term variation handling have been developed to date. The technique described performs gene name normalization by dictionary look‐up.

Which species is it? Species-driven gene name disambiguation using random walks over a mixture of adjacency matrices

The scientific literature contains a wealth of information about biological systems. Manual curation lacks the scalability to extract this information due to the ever-increasing numbers of papers being published. The development and application of text mining technologies has been proposed as a way of dealing with this problem. However, the inter-species ambiguity of the genomic nomenclature makes mapping of gene mentions identified in text to their corresponding Entrez gene identifiers an extremely difficult task. We propose a novel method, which transforms a MEDLINE record into a mixture of adjacency matrices; by performing a random walkover the resulting graph, we can perform multi-class supervised classification allowing the assignment of taxonomy identifiers to individual gene mentions. The ability to achieve good performance at this task has a direct impact on the performance of normalizing gene mentions to Entrez gene identifiers. Such graph mixtures add flexibility and allow us to generate probabilistic classification schemes that naturally reflect the uncertainties inherent, even in literature-derived data. Our method performs well in terms of both micro- and macro-averaged performance, achieving micro-F(1) of 0.76 and macro-F(1) of 0.36 on the publicly available DECA corpus. Re-curation of the DECA corpus was performed, with our method achieving 0.88 micro-F(1) and 0.51 macro-F(1). Our method improves over standard classification techniques [such as support vector machines (SVMs)] in a number of ways: flexibility, interpretability and its resistance to the effects of class bias in the training data. Good performance is achieved without the need for computationally expensive parse tree generation or 'bag of words classification'.

BIO-MOLECULAR EVENT EXTRACTION WITH MARKOV LOGIC

This article presents a novel approach to event extraction from biological text using Markov Logic. It can be described by three design decisions: (1) instead of building a pipeline using local classifiers, we design and learn a joint probabilistic model over events in a sentence; (2) instead of developing specific inference and learning algorithms for our joint model, we apply Markov Logic, a general purpose Statistical Relation Learning language, for this task; (3) we represent events as relations over the token indices of a sentence, as opposed to structures that relate event entities to gene or protein mentions. In this article, we extend our original work by providing an error analysis for binding events. Moreover, we investigate the impact of different loss functions to precision, recall and F-measure. Finally, we show how to extract events of different types that share the same event clue. This extension allowed us to improve our performance our performance even further, leading to the third best scores for task 1 (in close range to the second place) and the best results for task 2 with a 14% point margin.

Boosting performance of gene mention tagging system by hybrid methods

NER (Named Entity Recognition) in biomedical literature is presently one of the internationally concerned NLP (Natural Language Processing) research questions. In order to get higher performance, a hybrid experimental framework is presented for the gene mention tagging task. Six classifiers are firstly constructed by four toolkits (CRF++, YamCha, Maximum Entropy (ME) and MALLET) with different training methods and features sets, and then combined with three different hybrid methods respectively: simple set operation method, voting method and two layer stacking method. Experiments carried out on the corpus of BioCreative II GM task show that the three hybrid methods get the F-measure of 87.40%, 87.31% and 87.70% separately without any post-processing, which are all higher than those of any single ones. Our best hybrid method (two layer stacking method) achieves an F-measure of 88.42% after post-processing, which outperforms most of the state-of-the-art systems. We also discuss the influence on the performance of the ensemble system by the number, performance and divergence of single classifiers in each hybrid method, and give the corresponding analysis why our hybrid models can improve the performance.