Patricia G. Baker

An ontology for bioinformatics applications

MOTIVATION An ontology of biological terminology provides a model of biological concepts that can be used to form a semantic framework for many data storage, retrieval and analysis tasks. Such a semantic framework could be used to underpin a range of important bioinformatics tasks, such as the querying of heterogeneous bioinformatics sources or the systematic annotation of experimental results. RESULTS This paper provides an overview of an ontology [the Transparent Access to Multiple Biological Information Sources (TAMBIS) ontology or TaO] that describes a wide range of bioinformatics concepts. The present paper describes the mechanisms used for delivering the ontology and discusses the ontologys design and organization, which are crucial for maintaining the coherence of a large collection of concepts and their relationships. AVAILABILITY The TAMBIS system, which uses a subset of the TaO described here, is accessible over the Web via http://img.cs.man.ac.uk/tambis (although in the first instance, we will use a password mechanism to limit the load on our server). The complete model is also available on the Web at the above URL.

A classification of tasks in bioinformatics

MOTIVATION This paper reports on a survey of bioinformatics tasks currently undertaken by working biologists. The aim was to find the range of tasks that need to be supported and the components needed to do this in a general query system. This enabled a set of evaluation criteria to be used to assess both the biology and mechanical nature of general query systems. RESULTS A classification of the biological content of the tasks gathered offers a checklist for those tasks (and their specialisations) that should be offered in a general bioinformatics query system. This semantic analysis was contrasted with a syntactic analysis that revealed the small number of components required to describe all bioinformatics questions. Both the range of biological tasks and syntactic task components can be seen to provide a set of bioinformatics requirements for general query systems. These requirements were used to evaluate two bioinformatics query systems.

Query processing in the TAMBIS bioinformatics source integration system

Conducting bioinformatic analyses involves biologists in expressing requests over a range of highly heterogeneous information sources and software tools. Such activities are laborious, and require detailed knowledge of the data structures and call interfaces of the different sources. The TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) project seeks to make the diversity in data structures, call interfaces and locations of bioinformatics sources transparent to users. In TAMBIS, queries are expressed in terms of an ontology implemented using a description logic, and queries over the ontology are rewritten to a middleware level for execution over the diverse sources. The paper describes query processing in TAMBIS, focusing in particular on the way source-independent concepts in the ontology are related to source-dependent middleware calls, and describing how the planner identifies efficient ways of evaluating user queries.

Factors Associated With Kidney Disease Progression and Mortality in a Referred CKD Population

BACKGROUND Knowing how kidney disease progresses is important for decision making in patients with chronic kidney disease (CKD) and for designing clinical services. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS We examined renal function trajectories in CRISIS (Chronic Renal Insufficiency Standards Implementation Study), in which 1,325 patients with CKD stages 3-5 and mean age of 65.1 years were followed up prospectively for a median of 26 months after referral to a regional nephrology center in the United Kingdom. By protocol, estimated glomerular filtration rate was determined every 12 months. PREDICTORS CKD stage defined as estimated glomerular filtration rate ≥ 45 (stage 3a), 30-44 (3b), 15-29 (4), and < 15 (5) mL/min/1.73 m². OUTCOMES Onset of renal replacement therapy (RRT), death, the composite end point of RRT or death, or decreasing CKD stage. RESULTS During a median follow-up of 26 months, 13% reached the end point of RRT (5.1 events/100 patient-years), 20% died (9.6 deaths/100 patient-years), and 33% reached the combined end point of RRT or death (14.7 events/100 patient-years). For stage 3a, baseline prevalence and annual probabilities of decreasing CKD stage, RRT, and death were 18.0%, 0.41, 0.01, and 0.02, respectively. Corresponding values for stage 3b were 32.5%, 0.22, < 0.01, and 0.06; for stage 4, 36.5%, 0.17, 0.03, and 0.10; and for stage 5, 13.2%, zero (by definition), 0.31, and 0.08, respectively. Markov model projections suggested a steady decrease for proportions with stages 3a, 3b, and 4; a steady increase for death and RRT; and a biphasic pattern for (non-RRT) stage 5, with a plateau in the first 2 years followed by a steady decrease. LIMITATIONS Single-center observational study. CONCLUSION This study suggests that death and RRT are the dominant outcomes in patients referred for management of CKD and that most patients spend comparatively little time in late stages without RRT.

Hybrid Monte Carlo: an efficient algorithm for condensed matter simulation

A detailed comparison has been made of the performance of molecular dynamics and hybrid Monte Carlo simulation algorithms for calculating thermodynamic properties of 2D Lennard‐Jonesium. The hybrid Monte Carlo simulation required an order of magnitude fewer steps than the molecular dynamics simulation to calculate reproducible values of the specific heat. The ergodicity of the two algorithms was compared via the use of intermediate scattering functions. For classical systems the intermediate scattering functions should be real; however, a simple analysis demonstrates that this function will have a significant imaginary component when ergodicity breaks down. For q vectors near the zone boundary, the scattering functions are real for both algorithms. However, for q vectors near the zone center (i.e., harmonic, weakly coupled modes), the scattering function calculated via molecular dynamics had a significantly larger imaginary component than that calculated using hybrid Monte Carlo. Therefore, the hybrid Monte Carlo algorithm is more ergodic and samples phase space more efficiently than molecular dynamics for simulations of 2D Lennard‐Jonesium.

The use of eGFR and ACR to predict decline in renal function in people with diabetes

BACKGROUND There have been few attempts to estimate progression of kidney disease in people with diabetes in a single large population with predictive modelling. The aim of this study was to investigate the rate of progression of chronic kidney disease in people with diabetes according to their estimated glomerular filtration rate (eGFR) and presence of albuminuria. METHODS Data were collected on all people with diabetes in Salford, UK, where an eGFR could be calculated using the four-variable MDRD formula and urinary albumin-creatinine ratio (uACR) was available. All data between 2001 and 2007 were used in the model. Classification of albuminuria status was based on the average of their first two uACR measurements. A longitudinal mixed effect dynamic regression model was fitted to the data. Parameters were estimated by maximum likelihood. RESULTS For the analysis of the population, average progression of eGFR, uACR and drug prescribing were available in 3431 people. The regression model showed that in people with diabetes and macroalbuminuria, eGFR declined at 5.7% per annum, while the eGFR of those with microalbuminuria or without albuminuria declined at 1.5% and 0.3% per annum, respectively, independently of age (P < 0.0001). CONCLUSIONS The longitudinal effect of time on eGFR showed that people with diabetes and macroalbuminuria have an estimated 19 times more rapid decline in renal function compared with those without albuminuria. This study demonstrates that the progression of kidney disease in diabetic people without albuminuria is relatively benign compared with those with albuminuria.

Complex Query Formulation Over Diverse Information Sources in TAMBIS

Biologists increasingly need to ask complex questions over the large number of data and analysis tools that are available on the Internet. To do this, the individual resources need to be made to work together. The knowledge needed to accomplish this, for example about the locations of the sources and their capabilities, places barriers between biologists and the questions they would like to ask. The TAMBIS project (Transparent Access to Multiple Bioinformatics Information Sources) has sought to remove some of these barriers, thereby making the process of asking questions against multiple sources more straightforward. Central to the TAMBIS system is an ontology of bioinformatics and biological terms. Users express retrieval requests in terms of the concepts and relationships described in the ontology, rather than by making direct reference to individual sources. This allows TAMBIS to be used to formulate rich, declarative queries over multiple sources. The ontology is constructed in a manner that ensures only biologically meaningful queries can be posed. User’s queries are constructed using an interactive ontology browsing and query construction tool, and are rewritten by a query planner for evaluation using a wrapper layer. This paper provides an overview of the TAMBIS approach to source integration, focusing on the way the ontology is used to support query formulation and refinement.

Recent developments in biological sequence databases.

Biological sequence databases are currently being re-engineered to make them more efficient and easier to use. This re-engineering is also providing an infrastructure to make it easier to interrogate and integrate data from different sources. The net result of this effort should be a great improvement in the power and availability of bioinformatics resources to the general biology community.

TAMBIS Online: a bioinformatics source integration tool

Conducting bioinformatic analyses involves biologists in expressing requests over a range of heterogeneous information sources. The TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) project seeks to make the diversity in data structures, call interfaces and locations of bioinformatics sources transparent to users. TAMBIS is available at .

The languages of health in general practice electronic patient records: a Zipf’s law analysis

BackgroundNatural human languages show a power law behaviour in which word frequency (in any large enough corpus) is inversely proportional to word rank - Zipf’s law. We have therefore asked whether similar power law behaviours could be seen in data from electronic patient records.ResultsIn order to examine this question, anonymised data were obtained from all general practices in Salford covering a seven year period and captured in the form of Read codes. It was found that data for patient diagnoses and procedures followed Zipf’s law. However, the medication data behaved very differently, looking much more like a referential index. We also observed differences in the statistical behaviour of the language used to describe patient diagnosis as a function of an anonymised GP practice identifier.ConclusionsThis works demonstrate that data from electronic patient records does follow Zipf’s law. We also found significant differences in Zipf’s law behaviour in data from different GP practices. This suggests that computational linguistic techniques could become a useful additional tool to help understand and monitor the data quality of health records.