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1.  An expanded evaluation of protein function prediction methods shows an improvement in accuracy 
Jiang, Yuxiang | Oron, Tal Ronnen | Clark, Wyatt T. | Bankapur, Asma R. | D’Andrea, Daniel | Lepore, Rosalba | Funk, Christopher S. | Kahanda, Indika | Verspoor, Karin M. | Ben-Hur, Asa | Koo, Da Chen Emily | Penfold-Brown, Duncan | Shasha, Dennis | Youngs, Noah | Bonneau, Richard | Lin, Alexandra | Sahraeian, Sayed M. E. | Martelli, Pier Luigi | Profiti, Giuseppe | Casadio, Rita | Cao, Renzhi | Zhong, Zhaolong | Cheng, Jianlin | Altenhoff, Adrian | Skunca, Nives | Dessimoz, Christophe | Dogan, Tunca | Hakala, Kai | Kaewphan, Suwisa | Mehryary, Farrokh | Salakoski, Tapio | Ginter, Filip | Fang, Hai | Smithers, Ben | Oates, Matt | Gough, Julian | Törönen, Petri | Koskinen, Patrik | Holm, Liisa | Chen, Ching-Tai | Hsu, Wen-Lian | Bryson, Kevin | Cozzetto, Domenico | Minneci, Federico | Jones, David T. | Chapman, Samuel | BKC, Dukka | Khan, Ishita K. | Kihara, Daisuke | Ofer, Dan | Rappoport, Nadav | Stern, Amos | Cibrian-Uhalte, Elena | Denny, Paul | Foulger, Rebecca E. | Hieta, Reija | Legge, Duncan | Lovering, Ruth C. | Magrane, Michele | Melidoni, Anna N. | Mutowo-Meullenet, Prudence | Pichler, Klemens | Shypitsyna, Aleksandra | Li, Biao | Zakeri, Pooya | ElShal, Sarah | Tranchevent, Léon-Charles | Das, Sayoni | Dawson, Natalie L. | Lee, David | Lees, Jonathan G. | Sillitoe, Ian | Bhat, Prajwal | Nepusz, Tamás | Romero, Alfonso E. | Sasidharan, Rajkumar | Yang, Haixuan | Paccanaro, Alberto | Gillis, Jesse | Sedeño-Cortés, Adriana E. | Pavlidis, Paul | Feng, Shou | Cejuela, Juan M. | Goldberg, Tatyana | Hamp, Tobias | Richter, Lothar | Salamov, Asaf | Gabaldon, Toni | Marcet-Houben, Marina | Supek, Fran | Gong, Qingtian | Ning, Wei | Zhou, Yuanpeng | Tian, Weidong | Falda, Marco | Fontana, Paolo | Lavezzo, Enrico | Toppo, Stefano | Ferrari, Carlo | Giollo, Manuel | Piovesan, Damiano | Tosatto, Silvio C.E. | del Pozo, Angela | Fernández, José M. | Maietta, Paolo | Valencia, Alfonso | Tress, Michael L. | Benso, Alfredo | Di Carlo, Stefano | Politano, Gianfranco | Savino, Alessandro | Rehman, Hafeez Ur | Re, Matteo | Mesiti, Marco | Valentini, Giorgio | Bargsten, Joachim W. | van Dijk, Aalt D. J. | Gemovic, Branislava | Glisic, Sanja | Perovic, Vladmir | Veljkovic, Veljko | Veljkovic, Nevena | Almeida-e-Silva, Danillo C. | Vencio, Ricardo Z. N. | Sharan, Malvika | Vogel, Jörg | Kansakar, Lakesh | Zhang, Shanshan | Vucetic, Slobodan | Wang, Zheng | Sternberg, Michael J. E. | Wass, Mark N. | Huntley, Rachael P. | Martin, Maria J. | O’Donovan, Claire | Robinson, Peter N. | Moreau, Yves | Tramontano, Anna | Babbitt, Patricia C. | Brenner, Steven E. | Linial, Michal | Orengo, Christine A. | Rost, Burkhard | Greene, Casey S. | Mooney, Sean D. | Friedberg, Iddo | Radivojac, Predrag
Genome Biology  2016;17(1):184.
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.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-016-1037-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s13059-016-1037-6
PMCID: PMC5015320  PMID: 27604469
Protein function prediction; Disease gene prioritization
2.  TEES 2.2: Biomedical Event Extraction for Diverse Corpora 
BMC Bioinformatics  2015;16(Suppl 16):S4.
Background
The Turku Event Extraction System (TEES) is a text mining program developed for the extraction of events, complex biomedical relationships, from scientific literature. Based on a graph-generation approach, the system detects events with the use of a rich feature set built via dependency parsing. The TEES system has achieved record performance in several of the shared tasks of its domain, and continues to be used in a variety of biomedical text mining tasks.
Results
The TEES system was quickly adapted to the BioNLP'13 Shared Task in order to provide a public baseline for derived systems. An automated approach was developed for learning the underlying annotation rules of event type, allowing immediate adaptation to the various subtasks, and leading to a first place in four out of eight tasks. The system for the automated learning of annotation rules is further enhanced in this paper to the point of requiring no manual adaptation to any of the BioNLP'13 tasks. Further, the scikit-learn machine learning library is integrated into the system, bringing a wide variety of machine learning methods usable with TEES in addition to the default SVM. A scikit-learn ensemble method is also used to analyze the importances of the features in the TEES feature sets.
Conclusions
The TEES system was introduced for the BioNLP'09 Shared Task and has since then demonstrated good performance in several other shared tasks. By applying the current TEES 2.2 system to multiple corpora from these past shared tasks an overarching analysis of the most promising methods and possible pitfalls in the evolving field of biomedical event extraction are presented.
doi:10.1186/1471-2105-16-S16-S4
PMCID: PMC4642046  PMID: 26551925
BioNLP; event extraction; text mining
3.  Application of the EVEX resource to event extraction and network construction: Shared Task entry and result analysis 
BMC Bioinformatics  2015;16(Suppl 16):S3.
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.
In this paper, we describe our participation in the latest BioNLP Shared Task using the large-scale text mining resource EVEX. We participated in the Genia Event Extraction (GE) and Gene Regulation Network (GRN) tasks with two separate systems. In the GE task, we implemented a re-ranking approach to improve the precision of an existing event extraction system, incorporating features from the EVEX resource. In the GRN task, our system relied solely on the EVEX resource and utilized a rule-based conversion algorithm between the EVEX and GRN formats.
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.
In the GRN task, we ranked fifth in the official results with a strict/relaxed SER score of 0.92/0.81 respectively. To try and improve upon these results, we have implemented a novel machine learning based conversion system and benchmarked its performance against the original rule-based system.
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.
In the GE task we demonstrate that both the re-ranking approach and the word vectors can provide slight performance improvement. A manual evaluation of the re-ranking results pinpoints some of the challenges faced in applying large-scale text mining knowledge to event extraction.
doi:10.1186/1471-2105-16-S16-S3
PMCID: PMC4642107  PMID: 26551766
Text mining; Event extraction; Network construction; Large-scale data; Distributed vector representations of words
4.  Care episode retrieval: distributional semantic models for information retrieval in the clinical domain 
Patients' health related information is stored in electronic health records (EHRs) by health service providers. These records include sequential documentation of care episodes in the form of clinical notes. EHRs are used throughout the health care sector by professionals, administrators and patients, primarily for clinical purposes, but also for secondary purposes such as decision support and research. The vast amounts of information in EHR systems complicate information management and increase the risk of information overload. Therefore, clinicians and researchers need new tools to manage the information stored in the EHRs. A common use case is, given a - possibly unfinished - care episode, to retrieve the most similar care episodes among the records. This paper presents several methods for information retrieval, focusing on care episode retrieval, based on textual similarity, where similarity is measured through domain-specific modelling of the distributional semantics of words. Models include variants of random indexing and the semantic neural network model word2vec. Two novel methods are introduced that utilize the ICD-10 codes attached to care episodes to better induce domain-specificity in the semantic model. We report on experimental evaluation of care episode retrieval that circumvents the lack of human judgements regarding episode relevance. Results suggest that several of the methods proposed outperform a state-of-the art search engine (Lucene) on the retrieval task.
doi:10.1186/1472-6947-15-S2-S2
PMCID: PMC4474584  PMID: 26099735
5.  Regularized Machine Learning in the Genetic Prediction of Complex Traits 
PLoS Genetics  2014;10(11):e1004754.
doi:10.1371/journal.pgen.1004754
PMCID: PMC4230844  PMID: 25393026
6.  Multiple Different Defense Mechanisms Are Activated in the Young Transgenic Tobacco Plants Which Express the Full Length Genome of the Tobacco Mosaic Virus, and Are Resistant against this Virus 
PLoS ONE  2014;9(9):e107778.
Previously described transgenic tobacco lines express the full length infectious Tobacco mosaic virus (TMV) genome under the 35S promoter (Siddiqui et al., 2007. Mol Plant Microbe Interact, 20: 1489–1494). Through their young stages these plants exhibit strong resistance against both the endogenously expressed and exogenously inoculated TMV, but at the age of about 7–8 weeks they break into TMV infection, with typical severe virus symptoms. Infections with some other viruses (Potato viruses Y, A, and X) induce the breaking of the TMV resistance and lead to synergistic proliferation of both viruses. To deduce the gene functions related to this early resistance, we have performed microarray analysis of the transgenic plants during the early resistant stage, and after the resistance break, and also of TMV-infected wild type tobacco plants. Comparison of these transcriptomes to those of corresponding wild type healthy plants indicated that 1362, 1150 and 550 transcripts were up-regulated in the transgenic plants before and after the resistance break, and in the TMV-infected wild type tobacco plants, respectively, and 1422, 1200 and 480 transcripts were down-regulated in these plants, respectively. These transcriptome alterations were distinctly different between the three types of plants, and it appears that several different mechanisms, such as the enhanced expression of the defense, hormone signaling and protein degradation pathways contributed to the TMV-resistance in the young transgenic plants. In addition to these alterations, we also observed a distinct and unique gene expression alteration in these plants, which was the strong suppression of the translational machinery. This may also contribute to the resistance by slowing down the synthesis of viral proteins. Viral replication potential may also be suppressed, to some extent, by the reduction of the translation initiation and elongation factors eIF-3 and eEF1A and B, which are required for the TMV replication complex.
doi:10.1371/journal.pone.0107778
PMCID: PMC4171492  PMID: 25244327
7.  A large-scale evaluation of computational protein function prediction 
Radivojac, Predrag | Clark, Wyatt T | Ronnen Oron, Tal | Schnoes, Alexandra M | Wittkop, Tobias | Sokolov, Artem | Graim, Kiley | Funk, Christopher | Verspoor, Karin | Ben-Hur, Asa | Pandey, Gaurav | Yunes, Jeffrey M | Talwalkar, Ameet S | Repo, Susanna | Souza, Michael L | Piovesan, Damiano | Casadio, Rita | Wang, Zheng | Cheng, Jianlin | Fang, Hai | Gough, Julian | Koskinen, Patrik | Törönen, Petri | Nokso-Koivisto, Jussi | Holm, Liisa | Cozzetto, Domenico | Buchan, Daniel W A | Bryson, Kevin | Jones, David T | Limaye, Bhakti | Inamdar, Harshal | Datta, Avik | Manjari, Sunitha K | Joshi, Rajendra | Chitale, Meghana | Kihara, Daisuke | Lisewski, Andreas M | Erdin, Serkan | Venner, Eric | Lichtarge, Olivier | Rentzsch, Robert | Yang, Haixuan | Romero, Alfonso E | Bhat, Prajwal | Paccanaro, Alberto | Hamp, Tobias | Kassner, Rebecca | Seemayer, Stefan | Vicedo, Esmeralda | Schaefer, Christian | Achten, Dominik | Auer, Florian | Böhm, Ariane | Braun, Tatjana | Hecht, Maximilian | Heron, Mark | Hönigschmid, Peter | Hopf, Thomas | Kaufmann, Stefanie | Kiening, Michael | Krompass, Denis | Landerer, Cedric | Mahlich, Yannick | Roos, Manfred | Björne, Jari | Salakoski, Tapio | Wong, Andrew | Shatkay, Hagit | Gatzmann, Fanny | Sommer, Ingolf | Wass, Mark N | Sternberg, Michael J E | Škunca, Nives | Supek, Fran | Bošnjak, Matko | Panov, Panče | Džeroski, Sašo | Šmuc, Tomislav | Kourmpetis, Yiannis A I | van Dijk, Aalt D J | ter Braak, Cajo J F | Zhou, Yuanpeng | Gong, Qingtian | Dong, Xinran | Tian, Weidong | Falda, Marco | Fontana, Paolo | Lavezzo, Enrico | Di Camillo, Barbara | Toppo, Stefano | Lan, Liang | Djuric, Nemanja | Guo, Yuhong | Vucetic, Slobodan | Bairoch, Amos | Linial, Michal | Babbitt, Patricia C | Brenner, Steven E | Orengo, Christine | Rost, Burkhard | Mooney, Sean D | Friedberg, Iddo
Nature methods  2013;10(3):221-227.
Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based Critical Assessment of protein Function Annotation (CAFA) experiment. Fifty-four methods representing the state-of-the-art for protein function prediction were evaluated on a target set of 866 proteins from eleven organisms. Two findings stand out: (i) today’s best protein function prediction algorithms significantly outperformed widely-used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is significant need for improvement of currently available tools.
doi:10.1038/nmeth.2340
PMCID: PMC3584181  PMID: 23353650
8.  Large-Scale Event Extraction from Literature with Multi-Level Gene Normalization 
PLoS ONE  2013;8(4):e55814.
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.
doi:10.1371/journal.pone.0055814
PMCID: PMC3629104  PMID: 23613707
9.  University of Turku in the BioNLP'11 Shared Task 
BMC Bioinformatics  2012;13(Suppl 11):S4.
Background
We present a system for extracting biomedical events (detailed descriptions of biomolecular interactions) from research articles, developed for the BioNLP'11 Shared Task. Our goal is to develop a system easily adaptable to different event schemes, following the theme of the BioNLP'11 Shared Task: generalization, the extension of event extraction to varied biomedical domains. Our system extends our BioNLP'09 Shared Task winning Turku Event Extraction System, which uses support vector machines to first detect event-defining words, followed by detection of their relationships.
Results
Our current system successfully predicts events for every domain case introduced in the BioNLP'11 Shared Task, being the only system to participate in all eight tasks and all of their subtasks, with best performance in four tasks. Following the Shared Task, we improve the system on the Infectious Diseases task from 42.57% to 53.87% F-score, bringing performance into line with the similar GENIA Event Extraction and Epigenetics and Post-translational Modifications tasks. We evaluate the machine learning performance of the system by calculating learning curves for all tasks, detecting areas where additional annotated data could be used to improve performance. Finally, we evaluate the use of system output on external articles as additional training data in a form of self-training.
Conclusions
We show that the updated Turku Event Extraction System can easily be adapted to all presently available event extraction targets, with competitive performance in most tasks. The scope of the performance gains between the 2009 and 2011 BioNLP Shared Tasks indicates event extraction is still a new field requiring more work. We provide several analyses of event extraction methods and performance, highlighting potential future directions for continued development.
doi:10.1186/1471-2105-13-S11-S4
PMCID: PMC3384251  PMID: 22759458
10.  Semantically linking molecular entities in literature through entity relationships 
BMC Bioinformatics  2012;13(Suppl 11):S6.
Background
Text mining tools have gained popularity to process the vast amount of available research articles in the biomedical literature. It is crucial that such tools extract information with a sufficient level of detail to be applicable in real life scenarios. Studies of mining non-causal molecular relations attribute to this goal by formally identifying the relations between genes, promoters, complexes and various other molecular entities found in text. More importantly, these studies help to enhance integration of text mining results with database facts.
Results
We describe, compare and evaluate two frameworks developed for the prediction of non-causal or 'entity' relations (REL) between gene symbols and domain terms. For the corresponding REL challenge of the BioNLP Shared Task of 2011, these systems ranked first (57.7% F-score) and second (41.6% F-score). In this paper, we investigate the performance discrepancy of 16 percentage points by benchmarking on a related and more extensive dataset, analysing the contribution of both the term detection and relation extraction modules. We further construct a hybrid system combining the two frameworks and experiment with intersection and union combinations, achieving respectively high-precision and high-recall results. Finally, we highlight extremely high-performance results (F-score >90%) obtained for the specific subclass of embedded entity relations that are essential for integrating text mining predictions with database facts.
Conclusions
The results from this study will enable us in the near future to annotate semantic relations between molecular entities in the entire scientific literature available through PubMed. The recent release of the EVEX dataset, containing biomolecular event predictions for millions of PubMed articles, is an interesting and exciting opportunity to overlay these entity relations with event predictions on a literature-wide scale.
doi:10.1186/1471-2105-13-S11-S6
PMCID: PMC3384255  PMID: 22759460
11.  Exploring Biomolecular Literature with EVEX: Connecting Genes through Events, Homology, and Indirect Associations 
Advances in Bioinformatics  2012;2012:582765.
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.
doi:10.1155/2012/582765
PMCID: PMC3375141  PMID: 22719757
12.  Wrapper-based selection of genetic features in genome-wide association studies through fast matrix operations 
Background
Through the wealth of information contained within them, genome-wide association studies (GWAS) have the potential to provide researchers with a systematic means of associating genetic variants with a wide variety of disease phenotypes. Due to the limitations of approaches that have analyzed single variants one at a time, it has been proposed that the genetic basis of these disorders could be determined through detailed analysis of the genetic variants themselves and in conjunction with one another. The construction of models that account for these subsets of variants requires methodologies that generate predictions based on the total risk of a particular group of polymorphisms. However, due to the excessive number of variants, constructing these types of models has so far been computationally infeasible.
Results
We have implemented an algorithm, known as greedy RLS, that we use to perform the first known wrapper-based feature selection on the genome-wide level. The running time of greedy RLS grows linearly in the number of training examples, the number of features in the original data set, and the number of selected features. This speed is achieved through computational short-cuts based on matrix calculus. Since the memory consumption in present-day computers can form an even tighter bottleneck than running time, we also developed a space efficient variation of greedy RLS which trades running time for memory. These approaches are then compared to traditional wrapper-based feature selection implementations based on support vector machines (SVM) to reveal the relative speed-up and to assess the feasibility of the new algorithm. As a proof of concept, we apply greedy RLS to the Hypertension – UK National Blood Service WTCCC dataset and select the most predictive variants using 3-fold external cross-validation in less than 26 minutes on a high-end desktop. On this dataset, we also show that greedy RLS has a better classification performance on independent test data than a classifier trained using features selected by a statistical p-value-based filter, which is currently the most popular approach for constructing predictive models in GWAS.
Conclusions
Greedy RLS is the first known implementation of a machine learning based method with the capability to conduct a wrapper-based feature selection on an entire GWAS containing several thousand examples and over 400,000 variants. In our experiments, greedy RLS selected a highly predictive subset of genetic variants in a fraction of the time spent by wrapper-based selection methods used together with SVM classifiers. The proposed algorithms are freely available as part of the RLScore software library at http://users.utu.fi/aatapa/RLScore/.
doi:10.1186/1748-7188-7-11
PMCID: PMC3606421  PMID: 22551170
GWAS; Genome-wide association study; Machine learning; Feature selection
14.  Complex event extraction at PubMed scale 
Bioinformatics  2010;26(12):i382-i390.
Motivation: There has recently been a notable shift in biomedical information extraction (IE) from relation models toward the more expressive event model, facilitated by the maturation of basic tools for biomedical text analysis and the availability of manually annotated resources. The event model allows detailed representation of complex natural language statements and can support a number of advanced text mining applications ranging from semantic search to pathway extraction. A recent collaborative evaluation demonstrated the potential of event extraction systems, yet there have so far been no studies of the generalization ability of the systems nor the feasibility of large-scale extraction.
Results: This study considers event-based IE at PubMed scale. We introduce a system combining publicly available, state-of-the-art methods for domain parsing, named entity recognition and event extraction, and test the system on a representative 1% sample of all PubMed citations. We present the first evaluation of the generalization performance of event extraction systems to this scale and show that despite its computational complexity, event extraction from the entire PubMed is feasible. We further illustrate the value of the extraction approach through a number of analyses of the extracted information.
Availability: The event detection system and extracted data are open source licensed and available at http://bionlp.utu.fi/.
Contact: jari.bjorne@utu.fi
doi:10.1093/bioinformatics/btq180
PMCID: PMC2881365  PMID: 20529932
15.  All-paths graph kernel for protein-protein interaction extraction with evaluation of cross-corpus learning 
BMC Bioinformatics  2008;9(Suppl 11):S2.
Background
Automated extraction of protein-protein interactions (PPI) is an important and widely studied task in biomedical text mining. We propose a graph kernel based approach for this task. In contrast to earlier approaches to PPI extraction, the introduced all-paths graph kernel has the capability to make use of full, general dependency graphs representing the sentence structure.
Results
We evaluate the proposed method on five publicly available PPI corpora, providing the most comprehensive evaluation done for a machine learning based PPI-extraction system. We additionally perform a detailed evaluation of the effects of training and testing on different resources, providing insight into the challenges involved in applying a system beyond the data it was trained on. Our method is shown to achieve state-of-the-art performance with respect to comparable evaluations, with 56.4 F-score and 84.8 AUC on the AImed corpus.
Conclusion
We show that the graph kernel approach performs on state-of-the-art level in PPI extraction, and note the possible extension to the task of extracting complex interactions. Cross-corpus results provide further insight into how the learning generalizes beyond individual corpora. Further, we identify several pitfalls that can make evaluations of PPI-extraction systems incomparable, or even invalid. These include incorrect cross-validation strategies and problems related to comparing F-score results achieved on different evaluation resources. Recommendations for avoiding these pitfalls are provided.
doi:10.1186/1471-2105-9-S11-S2
PMCID: PMC2586751  PMID: 19025688
16.  Comparative analysis of five protein-protein interaction corpora 
BMC Bioinformatics  2008;9(Suppl 3):S6.
Background
Growing interest in the application of natural language processing methods to biomedical text has led to an increasing number of corpora and methods targeting protein-protein interaction (PPI) extraction. However, there is no general consensus regarding PPI annotation and consequently resources are largely incompatible and methods are difficult to evaluate.
Results
We present the first comparative evaluation of the diverse PPI corpora, performing quantitative evaluation using two separate information extraction methods as well as detailed statistical and qualitative analyses of their properties. For the evaluation, we unify the corpus PPI annotations to a shared level of information, consisting of undirected, untyped binary interactions of non-static types with no identification of the words specifying the interaction, no negations, and no interaction certainty.
We find that the F-score performance of a state-of-the-art PPI extraction method varies on average 19 percentage units and in some cases over 30 percentage units between the different evaluated corpora. The differences stemming from the choice of corpus can thus be substantially larger than differences between the performance of PPI extraction methods, which suggests definite limits on the ability to compare methods evaluated on different resources. We analyse a number of potential sources for these differences and identify factors explaining approximately half of the variance. We further suggest ways in which the difficulty of the PPI extraction tasks codified by different corpora can be determined to advance comparability. Our analysis also identifies points of agreement and disagreement in PPI corpus annotation that are rarely explicitly stated by the authors of the corpora.
Conclusions
Our comparative analysis uncovers key similarities and differences between the diverse PPI corpora, thus taking an important step towards standardization. In the course of this study we have created a major practical contribution in converting the corpora into a shared format. The conversion software is freely available at .
doi:10.1186/1471-2105-9-S3-S6
PMCID: PMC2349296  PMID: 18426551
17.  BioInfer: a corpus for information extraction in the biomedical domain 
BMC Bioinformatics  2007;8:50.
Background
Lately, there has been a great interest in the application of information extraction methods to the biomedical domain, in particular, to the extraction of relationships of genes, proteins, and RNA from scientific publications. The development and evaluation of such methods requires annotated domain corpora.
Results
We present BioInfer (Bio Information Extraction Resource), a new public resource providing an annotated corpus of biomedical English. We describe an annotation scheme capturing named entities and their relationships along with a dependency analysis of sentence syntax. We further present ontologies defining the types of entities and relationships annotated in the corpus. Currently, the corpus contains 1100 sentences from abstracts of biomedical research articles annotated for relationships, named entities, as well as syntactic dependencies. Supporting software is provided with the corpus. The corpus is unique in the domain in combining these annotation types for a single set of sentences, and in the level of detail of the relationship annotation.
Conclusion
We introduce a corpus targeted at protein, gene, and RNA relationships which serves as a resource for the development of information extraction systems and their components such as parsers and domain analyzers. The corpus will be maintained and further developed with a current version being available at .
doi:10.1186/1471-2105-8-50
PMCID: PMC1808065  PMID: 17291334
18.  Lexical adaptation of link grammar to the biomedical sublanguage: a comparative evaluation of three approaches 
BMC Bioinformatics  2006;7(Suppl 3):S2.
Background
We study the adaptation of Link Grammar Parser to the biomedical sublanguage with a focus on domain terms not found in a general parser lexicon. Using two biomedical corpora, we implement and evaluate three approaches to addressing unknown words: automatic lexicon expansion, the use of morphological clues, and disambiguation using a part-of-speech tagger. We evaluate each approach separately for its effect on parsing performance and consider combinations of these approaches.
Results
In addition to a 45% increase in parsing efficiency, we find that the best approach, incorporating information from a domain part-of-speech tagger, offers a statistically significant 10% relative decrease in error.
Conclusion
When available, a high-quality domain part-of-speech tagger is the best solution to unknown word issues in the domain adaptation of a general parser. In the absence of such a resource, surface clues can provide remarkably good coverage and performance when tuned to the domain. The adapted parser is available under an open-source license.
doi:10.1186/1471-2105-7-S3-S2
PMCID: PMC1764446  PMID: 17134475
19.  Contextual weighting for Support Vector Machines in literature mining: an application to gene versus protein name disambiguation 
BMC Bioinformatics  2005;6:157.
Background
The ability to distinguish between genes and proteins is essential for understanding biological text. Support Vector Machines (SVMs) have been proven to be very efficient in general data mining tasks. We explore their capability for the gene versus protein name disambiguation task.
Results
We incorporated into the conventional SVM a weighting scheme based on distances of context words from the word to be disambiguated. This weighting scheme increased the performance of SVMs by five percentage points giving performance better than 85% as measured by the area under ROC curve and outperformed the Weighted Additive Classifier, which also incorporates the weighting, and the Naive Bayes classifier.
Conclusion
We show that the performance of SVMs can be improved by the proposed weighting scheme. Furthermore, our results suggest that in this study the increase of the classification performance due to the weighting is greater than that obtained by selecting the underlying classifier or the kernel part of the SVM.
doi:10.1186/1471-2105-6-157
PMCID: PMC1180820  PMID: 15972097

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