GRISOTTO: A greedy approach to improve combinatorial algorithms for motif discovery with prior knowledge

<p>Abstract</p> <p>Background</p> <p>Position-specific priors (PSP) have been used with success to boost EM and Gibbs sampler-based motif discovery algorithms. PSP information has been computed from different sources, including orthologous conservation, DNA duplex stability, and nucleosome positioning. The use of prior information has not yet been used in the context of combinatorial algorithms. Moreover, priors have been used only independently, and the gain of combining priors from different sources has not yet been studied.</p> <p>Results</p> <p>We extend RISOTTO, a combinatorial algorithm for motif discovery, by post-processing its output with a greedy procedure that uses prior information. PSP's from different sources are combined into a scoring criterion that guides the greedy search procedure. The resulting method, called GRISOTTO, was evaluated over 156 yeast TF ChIP-chip sequence-sets commonly used to benchmark prior-based motif discovery algorithms. Results show that GRISOTTO is at least as accurate as other twelve state-of-the-art approaches for the same task, even without combining priors. Furthermore, by considering combined priors, GRISOTTO is considerably more accurate than the state-of-the-art approaches for the same task. We also show that PSP's improve GRISOTTO ability to retrieve motifs from mouse ChiP-seq data, indicating that the proposed algorithm can be applied to data from a different technology and for a higher eukaryote.</p> <p>Conclusions</p> <p>The conclusions of this work are twofold. First, post-processing the output of combinatorial algorithms by incorporating prior information leads to a very efficient and effective motif discovery method. Second, combining priors from different sources is even more beneficial than considering them separately.</p

The use of a compliant EHR when providing clinical pathway driven care to a subset of diabetic patients : recommendation from a working group

The Belgian National Health Insurance Institute (NHII) and other Healthcare Authorities intend to improve the quality of care through promoting clinical pathway driven care and by optimising cooperation between the responsible primary care physician and the diabetologist. Patients and healthcare professionals are granted some (financial) benefits when meeting the conditions defined in a mutual agreement. This article describes the conditions and the functional requirements to be met by an EHR to enable and to maximise the benefits of a clinical pathway driven patient care to a specific group of diabetic type 2 patients, based on a mandate issued by the NHII. The generic and specific functional requirements are then translated in test criteria for certification and prioritised in an implementation plan

Collecting information on the quality of prescribing in primary care using semi-automatic data extraction from GPs' electronic medical records

Objectives: To evaluate a semi-automatic data extraction from the electronic medical record (EMR) of general practitioners (GPs) through a comparison with a paper sheets data collection simultaneously used in a primary care research project on the quality of prescribing for osteoarthritis in the elderly. Subjects: One hundred and fifty-two GPs using five different EMR-software systems participated with the semi-automatic data extraction from the EMR and 233 GPs collected data with paper registration sheets. Methods: The proportion of patients with respectively a drug prescription, paracetamol, a non-steroidal anti-inflammatory drug (NSAID) and ibuprofen were compared between the semi-automatic extraction and the paper data collection and among the EMR-software systems. Results: Using the semi-automatic data extraction, a significantly lower proportion of patients on drugs was obtained compared to the paper data collection (adjusted OR: 0.31; 95% CI 0.25-0.39). However, the proportion of patients on a specific type of drug was comparable. Within the results from the semi-automatic extraction, the results were heterogeneous among the different EMR-software systems. Conclusions: The semi-automatic data extraction with multiple EMR-software systems proposed in this study seems suitable for quality of prescribing assessment in primary care. However, it may be less reliable when only a single EMR-software is used. (c) 2005 Elsevier Ireland Ltd. All rights reserved

The Evolutionarily Conserved Protein LAS1 Is Required for Pre-rRNA Processing at Both Ends of ITS2

Ribosome synthesis entails the formation of mature rRNAs from long precursor molecules, following a complex pre-rRNA processing pathway. Why the generation of mature rRNA ends is so complicated is unclear. Nor is it understood how pre-rRNA processing is coordinated at distant sites on pre-rRNA molecules. Here we characterized, in budding yeast and human cells, the evolutionarily conserved protein Las1. We found that, in both species, Las1 is required to process ITS2, which separates the 5.8S and 25S/28S rRNAs. In yeast, Las1 is required for pre-rRNA processing at both ends of ITS2. It is required for Rrp6-dependent formation of the 5.8S rRNA 3′ end and for Rat1-dependent formation of the 25S rRNA 5′ end. We further show that the Rat1-Rai1 5′-3′ exoribonuclease (exoRNase) complex functionally connects processing at both ends of the 5.8S rRNA. We suggest that pre-rRNA processing is coordinated at both ends of 5.8S rRNA and both ends of ITS2, which are brought together by pre-rRNA folding, by an RNA processing complex. Consistently, we note the conspicuous presence of ∼7- or 8-nucleotide extensions on both ends of 5.8S rRNA precursors and at the 5′ end of pre-25S RNAs suggestive of a protected spacer fragment of similar length