Diane E. Oliver

The GuideLine Interchange Format: A Model for Representing Guidelines

OBJECTIVE To allow exchange of clinical practice guidelines among institutions and computer-based applications. DESIGN The GuideLine Interchange Format (GLIF) specification consists of GLIF model and the GLIF syntax. The GLIF model is an object-oriented representation that consists of a set of classes for guideline entities, attributes for those classes, and data types for the attribute values. The GLIF syntax specifies the format of the test file that contains the encoding. METHODS Researchers from the InterMed Collaboratory at Columbia University, Harvard University (Brigham and Womens Hospital and Massachusetts General Hospital), and Stanford University analyzed four existing guideline systems to derive a set of requirements for guideline representation. The GLIF specification is a consensus representation developed through a brainstorming process. Four clinical guidelines were encoded in GLIF to assess its expressivity and to study the variability that occurs when two people from different sites encode the same guideline. RESULTS The encoders reported that GLIF was adequately expressive. A comparison of the encodings revealed substantial variability. CONCLUSION GLIF was sufficient to model the guidelines for the four conditions that were examined. GLIF needs improvement in standard representation of medical concepts, criterion logic, temporal information, and uncertainty.

Integrating genotype and phenotype information : an overview of the pharmGKB project

Pharmacogenetics seeks to explain how people respond in different ways to the same drug treatment. A classic example of the importance of pharmacogenomics is the variation in individual responses to the anti-leukemia drug, 6-mercaptopurine. Most people metabolize the drug quickly. Some individuals, with a genetic variation for the enzyme thiopurine methyltransferase (TPMT),1 do not. Consequently, they need lower doses of 6-mercaptopurine for effective treatment as normal doses can be lethal. One of the many promises of the human genome project is an ability to pharmacologically treat individuals in a more personalized rather than statistical manner.

The Unified Medical Language System: Toward a Collaborative Approach for Solving Terminologic Problems

The approach taken by the Unified Medical Language System (UMLS), in which disparate terminology systems are integrated, has allowed construction of an electronic thesaurus (the Metathesaurus) that avoids imposing any restrictions upon the content, structure, or semantics of the source terminologies. As such, the UMLS has served as a unifying paradigm by providing appropriate links among equivalent entities that are used in different contexts or for different purposes. It accordingly provides a vehicle through which possibly orthogonal semantic models can co-exist within a single framework. This framework provides a model for the collaborative evolution of biomedical terminology and allows a synergistic relationship between the UMLS and its source terminology systems.

Representation of change in controlled medical terminologies.

Computer-based systems that support health care require large controlled terminologies to manage names and meanings of data elements. These terminologies are not static, because change in health care is inevitable. To share data and applications in health care, we need standards not only for terminologies and concept representation, but also for representing change. To develop a principled approach to managing change, we analyze the requirements of controlled medical terminologies and consider features that frame knowledge-representation systems have to offer. Based on our analysis, we present a concept model, a set of change operations, and a change-documentation model that may be appropriate for controlled terminologies in health care. We are currently implementing our modeling approach within a computational architecture.

Automating Data Acquisition into Ontologies from Pharmacogenetics Relational Data Sources Using Declarative Object Definitions and XML

Ontologies are useful for organizing large numbers of concepts having complex relationships, such as the breadth of genetic and clinical knowledge in pharmacogenomics. But because ontologies change and knowledge evolves, it is time consuming to maintain stable mappings to external data sources that are in relational format. We propose a method for interfacing ontology models with data acquisition from external relational data sources. This method uses a declarative interface between the ontology and the data source, and this interface is modeled in the ontology and implemented using XML schema. Data is imported from the relational source into the ontology using XML, and data integrity is checked by validating the XML submission with an XML schema. We have implemented this approach in PharmGKB (http://www.pharmgkb.org/), a pharmacogenetics knowledge base. Our goals were to (1) import genetic sequence data, collected in relational format, into the pharmacogenetics ontology, and (2) automate the process of updating the links between the ontology and data acquisition when the ontology changes. We tested our approach by linking PharmGKB with data acquisition from a relational model of genetic sequence information. The ontology subsequently evolved, and we were able to rapidly update our interface with the external data and continue acquiring the data. Similar approaches may be helpful for integrating other heterogeneous information sources in order make the diversity of pharmacogenetics data amenable to computational analysis.

ONTOLOGY DEVELOPMENT FOR A PHARMACOGENETICS KNOWLEDGE BASE

Research directed toward discovering how genetic factors influence a patients response to drugs requires coordination of data produced from laboratory experiments, computational methods, and clinical studies. A public repository of pharmacogenetic data should accelerate progress in the field of pharmacogenetics by organizing and disseminating public datasets. We are developing a pharmacogenetics knowledge base (PharmGKB) to support the storage and retrieval of both experimental data and conceptual knowledge. PharmGKB is an Internet-based resource that integrates complex biological, pharmacological, and clinical data in such a way that researchers can submit their data and users can retrieve information to investigate genotype-phenotype correlations. Successful management of the names, meaning, and organization of concepts used within the system is crucial. We have selected a frame-based knowledge-representation system for development of an ontology of concepts and relationships that represent the domain and that permit storage of experimental data. Preliminary experience shows that the ontology we have developed for gene-sequence data allows us to accept, store, and query data submissions.

Tools for loading MEDLINE into a local relational database

BackgroundResearchers who use MEDLINE for text mining, information extraction, or natural language processing may benefit from having a copy of MEDLINE that they can manage locally. The National Library of Medicine (NLM) distributes MEDLINE in eXtensible Markup Language (XML)-formatted text files, but it is difficult to query MEDLINE in that format. We have developed software tools to parse the MEDLINE data files and load their contents into a relational database. Although the task is conceptually straightforward, the size and scope of MEDLINE make the task nontrivial. Given the increasing importance of text analysis in biology and medicine, we believe a local installation of MEDLINE will provide helpful computing infrastructure for researchers.ResultsWe developed three software packages that parse and load MEDLINE, and ran each package to install separate instances of the MEDLINE database. For each installation, we collected data on loading time and disk-space utilization to provide examples of the process in different settings. Settings differed in terms of commercial database-management system (IBM DB2 or Oracle 9i), processor (Intel or Sun), programming language of installation software (Java or Perl), and methods employed in different versions of the software. The loading times for the three installations were 76 hours, 196 hours, and 132 hours, and disk-space utilization was 46.3 GB, 37.7 GB, and 31.6 GB, respectively. Loading times varied due to a variety of differences among the systems. Loading time also depended on whether data were written to intermediate files or not, and on whether input files were processed in sequence or in parallel. Disk-space utilization depended on the number of MEDLINE files processed, amount of indexing, and whether abstracts were stored as character large objects or truncated.ConclusionsRelational database (RDBMS) technology supports indexing and querying of very large datasets, and can accommodate a locally stored version of MEDLINE. RDBMS systems support a wide range of queries and facilitate certain tasks that are not directly supported by the application programming interface to PubMed. Because there is variation in hardware, software, and network infrastructures across sites, we cannot predict the exact time required for a user to load MEDLINE, but our results suggest that performance of the software is reasonable. Our database schemas and conversion software are publicly available at http://biotext.berkeley.edu.

Indexing pharmacogenetic knowledge on the World Wide Web.

A key challenge for pharmacogenetics is the creation of databases to store, analyse and disseminate important datasets in order to catalyse research and training. Most successful databases have a limited scope: Genbank contains DNA sequences [1]; the Protein Data Bank contains the three-dimensional coordinates of macromolecules [2]; the Online Mendelian Inheritance in Man contains a record of human genetic disease [3]; and PubMED contains the biomedical literature [4]. This limited scope is a great strength, because the information can be stored, searched and analysed using a few powerful tools, and the users of these databases know exactly what to expect. Databases for pharmacogenetics and pharmacogenomics will have much more diversity. Pharmacogenetic data involve phenotypes that are as diverse as the assays we invent to measure them. Thus, it is unclear what a user should expect from a pharmacogenetics database, and yet a public repository of pharmacogenetic data is critical to establish a core dataset for the field upon which we can build new analyses and new hypotheses [1]. Clearly, successful databases for pharmacogenetics must employ some sort of classification of phenotypes that is general purpose, yet extensible to include undefined characterizations of phenotype.