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PubMed2006

Development of grid frameworks for clinical trials and epidemiological studies.

E-Health initiatives such as electronic clinical trials and epidemiological studies require access to and usage of a range of both clinical and other data sets. Such data sets are typically only available over many heterogeneous domains where a plethora of often legacy based or in-house/bespoke IT solutions exist. Considerable efforts and investments are being made across the UK to upgrade the IT infrastructures across the National Health Service (NHS) such as the National Program for IT in the NHS (NPFIT) [1]. However, it is the case that currently independent and largely non-interoperable IT solutions exist across hospitals, trusts, disease registries and GP practices - this includes security as well as more general compute and data infrastructures. Grid technology allows issues of distribution and heterogeneity to be overcome, however the clinical trials domain places special demands on security and data which hitherto the Grid community have not satisfactorily addressed. These challenges are often common across many studies and trials hence the development of a re-usable framework for creation and subsequent management of such infrastructures is highly desirable. In this paper we present the challenges in developing such a framework and outline initial scenarios and prototypes developed within the MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) project [2].

Access to Information↗
PubMed1996

List update processing (LUP)--solving the sequence database update problem.

Sequence databases of today require frequent updating. Mirror procedures to copy incrementally updated databases as cumulative sets are the preferred method and can be implemented by straightforward scripting. However, limited bandwidth of networks and the increase of data require more powerful paradigms to reduce the workload reliably. We suggest the List Update Processing (LUP) principle. The system has been implemented on an experimental basis to update the Swiss EMBnet Node (BioComputing Basel, CH) with data from the European Bioinformatics Institute (EMBL Outstation, Hinxton Hall, UK). The results obtained from the prototype suggest to expand the system to several sites.

CD-ROM↗
PubMed1997

Ubiquitous distributed objects with CORBA.

Database interoperation is becoming a bottleneck for the research community in biology. In this paper, we first discuss the question of interoperability and give a brief overview of CORBA. Then, an example is explained in some detail: a simple but realistic data bank of STSs is implemented. The Object Request Broker is the media for communication between an object server (the data bank) and a client (possibly a genome center). Since CORBA enables easy development of networked applications, we meant this paper to provide an incentive for the bioinformatics community to develop distributed objects.

Base Sequence↗
PubMed1997

An approach to detection of protein structural motifs using an encoding scheme of backbone conformations.

This paper presents an approach to detection of protein structural motifs. In our approach, first all protein backbone conformations are converted into character strings using an encoding scheme. Then we use the Smith-Waterman local alignment algorithm to detect common structural motifs. By comparing results with the PROSITE regular expression patterns, our method can detect several motifs which the PROSITE patterns fail to detect.

Amino Acid Sequence↗
PubMed1997

Using the radial distributions of physical features to compare amino acid environments and align amino acid sequences.

We have performed a comprehensive analysis of the microenvironments surrounding the twenty amino acids. Our analysis includes comparison of amino acid environments with random control environments as well as with each of the other amino acid environments. We describe the amino acid environments with a set of 21 features summarizing atomic, chemical group, residue, and secondary structural features. The environments are divided into radial shells of 1 A thickness to represent the distance of the features from the amino acid C beta atoms. We make the results of our analysis available graphically over the world wide web. To illustrate the validity and utility of our analysis, we used the amino acid comparative profiles to construct a substitution matrix, the WAC matrix, based on a simple summary of the computed environmental differences. We compared our matrix to BLOSUM62 and PAM250 in BLAST searches with query sequences selected from 39 protein families found in the PROSITE database. Although BLOSUM62 was the most sensitive matrix overall, our matrix was more sensitive for some families, and exhibited overall performance similar to PAM250. Our results suggest that the radial distribution of biochemical and biophysical features is useful for comparing amino acid environments, and that similarity matrices based on the geometric distribution of features around amino acids may produce improved search sensitivity.

Amino Acid Sequence↗
PubMed1998

"Virtual" clinical trials: case control experiments utilizing a health services research workstation.

We created an interface to a growing repository of clinical and administrative information to facilitate the design and execution of case-control experiments. The system enables knowledgeable users to generate and test hypotheses regarding associations among diseases and outcomes. The intuitive interface allows the user to specify criteria for selecting cases and defining putative risks. The repository contains comprehensive administrative and selected clinical information on all ambulatory and emergency department visits as well as hospital admissions since 1994. We tested the workstation's ability to determine relationships between outpatient diagnoses including hypertension, osteoarthritis and hypercholesterolemia with the occurrence of admissions for stroke and myocardial infarction and achieved results consistent with published studies. Successful implementation of this Health Services Research Workstation will allow "virtual" clinical trials to validate the results of formal clinical trials on a local population and may provide meaningful analyses of data when formal clinical trials are not feasible.

Case-Control Studies↗
PubMed1998

Automatic query mapping among genomic databases: a pilot exploration.

As databases in the human genome project proliferate, it is important for users of one genomic database to identify similar or inconsistent data in other autonomously developed genomic databases. To do so, the user needs to issue the same query across multiple databases. We describe an approach that allows a query issued against one database to be automatically mapped to an equivalent query against another structurally different database. Our approach features two components: 1) a database designed to capture knowledge (metadata) that describes the correspondences among individual database components and 2) a module that utilizes the metadata to perform query mappings. As a demonstration, we apply our query mapping approach to two chromosome map databases (DB/12 and GDB).

Algorithms↗
PubMed2005

Number of embryos for transfer after IVF and ICSI: a Cochrane review.

BACKGROUND: The most common complication of IVF is multiple pregnancy, which occurs in 25% of pregnancies following the transfer of two embryos. Single embryo transfer can minimize twin pregnancies but could also lower live birth rates. Our aim was to perform a systematic review of randomized trials to determine the effectiveness of single versus double embryo transfer. METHODS: Cochrane Collaboration review methods were followed. Randomized controlled trials comparing single and double embryo transfers were identified by searching Medline, EMBASE and the Cochrane register of controlled trials. Contents of specialist journals and proceedings from meetings of relevant societies were hand searched. Data were pooled with Rev Man software using the Peto-modified Mantel-Hanzel method. RESULTS: Pooled results from four trials indicate that although double embryo transfer leads to a higher live birth rate per woman [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.47-2.55] in a fresh IVF cycle, comparable results are obtained by subsequent transfer of a frozen embryo (OR 1.19, 95% CI 0.87-1.62). The multiple pregnancy rate is significantly higher (OR 62.83, 95% CI 8.52-463.57) after double embryo transfer. CONCLUSIONS: Single embryo transfer significantly reduces the risk of multiple pregnancy, but also decreases the chance of live birth in a fresh IVF cycle. Subsequent replacement of a single frozen embryo achieves a live birth rate comparable with double embryo transfer.

Adult↗
PubMed2000

Contact Allergen Avoidance Program: a topical skin care product database.

Management of allergic contact dermatitis can be challenging for patients because of difficulties they encounter while attempting to avoid antigens identified by patch tests. The disorder is commonly caused by fragrances, preservatives, or other ingredients found in skin care products. After patch testing, the clinician routinely educates the patient on the sources of the antigens to which he or she is sensitive. Because typical allergen names are long, are difficult to spell, commonly have numerous complex synonyms, and are often frankly intimidating for patients, compliance with allergen avoidance is frequently problematic. We have developed a Contact Allergen Avoidance Program database tool that generates an extensive list of skin care products that are free of the given patient's allergens. It has been used clinically for 2 years to facilitate successful antigen avoidance and has been positively received by both patients and clinicians.

Allergens↗