Inherited disorder phenotypes: controlled annotation and statistical analysis for knowledge mining from gene lists

BACKGROUND: Analysis of inherited diseases and their associated phenotypes is of great importance to gain knowledge of underlying genetic interactions and could ultimately give clinically useful insights into disease processes, including complex diseases influenced by multiple genetic loci. Nevertheless, to date few computational contributions have been proposed for this purpose, mainly due to lack of controlled clinical information easily accessible and structured for computational genome-wise analyses. To allow performing phenotype analyses of inherited disorder related genes we implemented new original modules within GFINDer , a Web system we previously developed that dynamically aggregates functional annotations of user uploaded gene lists and allows performing their statistical analysis and mining. RESULTS: New GFINDer modules allow annotating large numbers of user classified biomolecular sequence identifiers with morbidity and clinical information, classifying them according to genetic disease phenotypes and their locations of occurrence, and statistically analyzing the obtained classifications. To achieve this we exploited, normalized and structured the information present in textual form in the Clinical Synopsis sections of the Online Mendelian Inheritance in Man (OMIM) databank. Such valuable information delineates numerous signs and symptoms accompanying many genetic diseases and it is divided into phenotype location categories, either by organ system or type of finding. CONCLUSION: Supporting phenotype analyses of inherited diseases and biomolecular functional evaluations, GFINDer facilitates a genomic approach to the understanding of fundamental biological processes and complex cellular mechanisms underlying patho-physiological phenotypes

The Impact of Directionality in Predications on Text Mining

The number of publications in biomedicine is increasing enormously each year. To help researchers digest the information in these documents, text mining tools are being developed that present co-occurrence relations between concepts. Statistical measures are used to mine interesting subsets of relations. We demonstrate how directionality of these relations affects interestingness. Support and confidence, simple data mining statistics, are used as proxies for interestingness metrics. We first built a test bed of 126,404 directional relations extracted from biomedical abstracts, which we represent as graphs containing a central starting concept and 2 rings of associated relations. We manipulated directionality in four ways and randomly selected 100 starting concepts as a test sample for each graph type. Finally, we calculated the number of relations and their support and confidence. Variation in directionality significantly affected the number of relations as well as the support and confidence of the four graph types

Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

BACKGROUND: Genomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease. RESULTS: The filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing. In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease in several important databases on genetic disorders. CONCLUSION: Information based on the proximity postprocessing method we suggest is of sufficient quality to be profitably used for subsequent applications aimed at uncovering new biomedical knowledge. Although proximity filtering is only marginally effective for enhancing the precision of relations extracted with co-occurrence processing, it is likely to benefit methods based, even partially, on syntactic structure, regardless of the relation

Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

BACKGROUND: Genomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease. RESULTS: The filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing. In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease in several important databases on genetic disorders. CONCLUSION: Information based on the proximity postprocessing method we suggest is of sufficient quality to be profitably used for subsequent applications aimed at uncovering new biomedical knowledge. Although proximity filtering is only marginally effective for enhancing the precision of relations extracted with co-occurrence processing, it is likely to benefit methods based, even partially, on syntactic structure, regardless of the relation

OpenDMAP: An open source, ontology-driven concept analysis engine, with applications to capturing knowledge regarding protein transport, protein interactions and cell-type-specific gene expression

<p>Abstract</p> <p>Background</p> <p>Information extraction (IE) efforts are widely acknowledged to be important in harnessing the rapid advance of biomedical knowledge, particularly in areas where important factual information is published in a diverse literature. Here we report on the design, implementation and several evaluations of OpenDMAP, an ontology-driven, integrated concept analysis system. It significantly advances the state of the art in information extraction by leveraging knowledge in ontological resources, integrating diverse text processing applications, and using an expanded pattern language that allows the mixing of syntactic and semantic elements and variable ordering.</p> <p>Results</p> <p>OpenDMAP information extraction systems were produced for extracting protein transport assertions (transport), protein-protein interaction assertions (interaction) and assertions that a gene is expressed in a cell type (expression). Evaluations were performed on each system, resulting in F-scores ranging from .26 – .72 (precision .39 – .85, recall .16 – .85). Additionally, each of these systems was run over all abstracts in MEDLINE, producing a total of 72,460 transport instances, 265,795 interaction instances and 176,153 expression instances. </p> <p>Conclusion</p> <p>OpenDMAP advances the performance standards for extracting protein-protein interaction predications from the full texts of biomedical research articles. Furthermore, this level of performance appears to generalize to other information extraction tasks, including extracting information about predicates of more than two arguments. The output of the information extraction system is always constructed from elements of an ontology, ensuring that the knowledge representation is grounded with respect to a carefully constructed model of reality. The results of these efforts can be used to increase the efficiency of manual curation efforts and to provide additional features in systems that integrate multiple sources for information extraction. The open source OpenDMAP code library is freely available at <url>http://bionlp.sourceforge.net/</url></p

Automatic extraction of biomolecular interactions: an empirical approach

Background We describe a method for extracting data about how biomolecule pairs interact from texts. This method relies on empirically determined characteristics of sentences. The characteristics are efficient to compute, making this approach to extraction of biomolecular interactions scalable. The results of such interaction mining can support interaction network annotation, question answering, database construction, and other applications. Results We constructed a software system to search MEDLINE for sentences likely to describe interactions between given biomolecules. The system extracts a list of the interaction-indicating terms appearing in those sentences, then ranks those terms based on their likelihood of correctly characterizing how the biomolecules interact. The ranking process uses a tf-idf (term frequency-inverse document frequency) based technique using empirically derived knowledge about sentences, and was applied to the MEDLINE literature collection. Software was developed as part of the MetNet toolkit (http://www.metnetdb.org). Conclusions Specific, efficiently computable characteristics of sentences about biomolecular interactions were analyzed to better understand how to use these characteristics to extract how biomolecules interact. The text empirics method that was investigated, though arising from a classical tradition, has yet to be fully explored for the task of extracting biomolecular interactions from the literature. The conclusions we reach about the sentence characteristics investigated in this work, as well as the technique itself, could be used by other systems to provide evidence about putative interactions, thus supporting efforts to maximize the ability of hybrid systems to support such tasks as annotating and constructing interaction networks

Extraction of semantic biomedical relations from text using conditional random fields

<p>Abstract</p> <p>Background</p> <p>The increasing amount of published literature in biomedicine represents an immense source of knowledge, which can only efficiently be accessed by a new generation of automated information extraction tools. Named entity recognition of well-defined objects, such as genes or proteins, has achieved a sufficient level of maturity such that it can form the basis for the next step: the extraction of relations that exist between the recognized entities. Whereas most early work focused on the mere detection of relations, the classification of the type of relation is also of great importance and this is the focus of this work. In this paper we describe an approach that extracts both the existence of a relation and its type. Our work is based on Conditional Random Fields, which have been applied with much success to the task of named entity recognition.</p> <p>Results</p> <p>We benchmark our approach on two different tasks. The first task is the identification of semantic relations between diseases and treatments. The available data set consists of manually annotated PubMed abstracts. The second task is the identification of relations between genes and diseases from a set of concise phrases, so-called GeneRIF (Gene Reference Into Function) phrases. In our experimental setting, we do not assume that the entities are given, as is often the case in previous relation extraction work. Rather the extraction of the entities is solved as a subproblem. Compared with other state-of-the-art approaches, we achieve very competitive results on both data sets. To demonstrate the scalability of our solution, we apply our approach to the complete human GeneRIF database. The resulting gene-disease network contains 34758 semantic associations between 4939 genes and 1745 diseases. The gene-disease network is publicly available as a machine-readable RDF graph.</p> <p>Conclusion</p> <p>We extend the framework of Conditional Random Fields towards the annotation of semantic relations from text and apply it to the biomedical domain. Our approach is based on a rich set of textual features and achieves a performance that is competitive to leading approaches. The model is quite general and can be extended to handle arbitrary biological entities and relation types. The resulting gene-disease network shows that the GeneRIF database provides a rich knowledge source for text mining. Current work is focused on improving the accuracy of detection of entities as well as entity boundaries, which will also greatly improve the relation extraction performance.</p