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Biomedical subjects

Peter Schattner

Publications and source records attributed to Peter Schattner.

14 recordsLinked to original sources
PubMed2006

Regions of extreme synonymous codon selection in mammalian genes.

Recently there has been increasing evidence that purifying selection occurs among synonymous codons in mammalian genes. This selection appears to be a consequence of either cis-regulatory motifs, such as exonic splicing enhancers (ESEs), or mRNA secondary structures, being superimposed on the coding sequence of the gene. We have developed a program to identify regions likely to be enriched for such motifs by searching for extended regions of extreme codon conservation between homologous genes of related species. Here we present the results of applying this approach to five mammalian species (human, chimpanzee, mouse, rat and dog). Even with very conservative selection criteria, we find over 200 regions of extreme codon conservation, ranging in length from 60 to 178 codons. The regions are often found within genes involved in DNA-binding, RNA-binding or zinc-ion-binding. They are highly depleted for synonymous single nucleotide polymorphisms (SNPs) but not for non-synonymous SNPs, further indicating that the observed codon conservation is being driven by negative selection. Forty-three percent of the regions overlap conserved alternative transcript isoforms and are enriched for known ESEs. Other regions are enriched for TpA dinucleotides and may contain conserved motifs/structures relating to mRNA stability and/or degradation. We anticipate that this tool will be useful for detecting regions enriched in other classes of coding-sequence motifs and structures as well.

Alternative Splicing↗
PubMed2006

The principles of guiding by RNA: chimeric RNA-protein enzymes.

The non-protein-coding transcriptional output of the cell is far greater than previously thought. Although the functions, if any, of the vast majority of these RNA transcripts remain elusive, out of those for which functions have already been established, most act as RNA guides for protein enzymes. Common features of these RNAs provide clues about the evolutionary constraints that led to the development of RNA-guided proteins and the specific biological environments in which target specificity and diversity are most crucial to the cell.

Animals↗
PubMed2006

An update on the etiology and epidemiology of diabetes mellitus.

Diabetes mellitus is one of the most common endocrine disorders affecting almost 6% of the world's population. The number of diabetic patients will reach 300 million in 2025 (International Diabetes Federation, 2001). More than 97% of these patients will have type II diabetes. The projected increase in the number of diabetic patients will strain the capabilities of healthcare providers the world over. Thus it is of paramount importance to revisit the causes and epidemiology of diabetes mellitus. Diabetes mellitus is caused by both environmental and genetic factors. The environmental factors that may lead to the development of diabetes mellitus include physical inactivity, drugs and toxic agents, obesity, viral infection, and location. While type I diabetes is not a genetically predestined disease, an increased susceptibility can be inherited. Genetic susceptibility plays a crucial role in the etiology and manifestation of type II diabetes, with concordance in monozygotic twins approaching 100%. Genetic factors may have to be modified by environmental factors for diabetes mellitus to become overt. An individual with a susceptible gene may become diabetic if environmental factors modify the expression of these genes. Since there is an increase in the trend at which diabetes prevail, it is evident that environmental factors are playing a more increasing role in the cause of diabetes mellitus. The incidence of type I diabetes ranged from 1.9 to 7.0/100,000/yr in Africa, 0.13 to 10/100,000/yr in Asia, approximately 4.4/100,000/yr in Australasia, 3.4 to 36/100,000/yr in Europe, 2.62 to 20.18/100,000/yr in the Middle East, 7.61 to 25.7/100,000/yr in North America, and 1.27 to 18/100,000/yr in South America. The epidemiology of type II diabetes is equally bleak. The prevalence of type II diabetes ranged from 0.3 to 17.9% in Africa, 1.2 to 14.6% in Asia, 0.7 to 11.6% in Europe, 4.6 to 40% in the Middle East, 6.69 to 28.2% in North America, and 2.01 to 17.4% in South America.

Africa↗
PubMed2006

A computational screen for mammalian pseudouridylation guide H/ACA RNAs.

The box H/ACA RNA gene family is one of the largest non-protein-coding gene families in eukaryotes and archaea. Recently, we developed snoGPS, a computational screening program for H/ACA snoRNAs, and applied it to Saccharomyces cerevisiae. We report here results of extending our method to screen for H/ACA RNAs in multiple large genomes of related species, and apply it to the human, mouse, and rat genomes. Because of the 250-fold larger search space compared to S. cerevisiae, significant enhancements to our algorithms were required. Complementing extensive cloning experiments performed by others, our findings include the detection and experimental verification of seven new mammalian H/ACA RNAs and the prediction of 23 new H/ACA RNA pseudouridine guide assignments. These assignments include four for H/ACA RNAs previously classified as orphan H/ACA RNAs with no known targets. We also determined systematic syntenic conservation among human and mouse H/ACA RNAs. With this work, 82 of 97 ribosomal RNA pseudouridines and 18 of 32 spliceosomal RNA pseudouridines in mammals have been linked to H/ACA guide RNAs.

Algorithms↗
PubMed2006

Do GPs use electronic mental health resources? - a qualitative study.

BACKGROUND: The Better Outcomes in Mental Health Care (BOMHC) initiative encourages general practitioners to use electronic mental health resources (EMHRs) during consultation with patients requiring psychological assistance. However, there is little data on GPs' acceptance and use of EMHRs. METHOD: Semistructured interviews were conducted with 27 GPs to determine their attitude toward EMHRs, and their use during consultation with patients. RESULTS: Few GPs reported frequently using EMHRs in consultation. Identified barriers to use included lack of familiarity with information technology, and insufficient knowledge of available resources. Identified advantages of electronic resources included high patient acceptance, time efficiency, and improved quality of information. DISCUSSION: General practitioners recognise several advantages of utilising electronic resources for managing patients with mental illness. However, GPs are not sufficiently familiar with electronic resources to use them effectively. This could be overcome by education.

Attitude of Health Personnel↗
PubMed2005

The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs.

Transfer RNAs (tRNAs) and small nucleolar RNAs (snoRNAs) are two of the largest classes of non-protein-coding RNAs. Conventional gene finders that detect protein-coding genes do not find tRNA and snoRNA genes because they lack the codon structure and statistical signatures of protein-coding genes. Previously, we developed tRNAscan-SE, snoscan and snoGPS for the detection of tRNAs, methylation-guide snoRNAs and pseudouridylation-guide snoRNAs, respectively. tRNAscan-SE is routinely applied to completed genomes, resulting in the identification of thousands of tRNA genes. Snoscan has successfully detected methylation-guide snoRNAs in a variety of eukaryotes and archaea, and snoGPS has identified novel pseudouridylation-guide snoRNAs in yeast and mammals. Although these programs have been quite successful at RNA gene detection, their use has been limited by the need to install and configure the software packages on UNIX workstations. Here, we describe online implementations of these RNA detection tools that make these programs accessible to a wider range of research biologists. The tRNAscan-SE, snoscan and snoGPS servers are available at http://lowelab.ucsc.edu/tRNAscan-SE/, http://lowelab.ucsc.edu/snoscan/ and http://lowelab.ucsc.edu/snoGPS/, respectively.

Genomics↗
PubMed2005

Non-coding RNAs: hope or hype?

The past four years have seen an explosion in the number of detected RNA transcripts with no apparent protein-coding potential. This has led to speculation that non-protein-coding RNAs (ncRNAs) might be as important as proteins in the regulation of vital cellular functions. However, there has been significantly less progress in actually demonstrating the functions of these transcripts. In this article, we review the results of recent experiments that show that transcription of non-protein-coding RNA is far more widespread than was previously anticipated. Although some ncRNAs act as molecular switches that regulate gene expression, the function of many ncRNAs is unknown. New experimental and computational approaches are emerging that will help determine whether these newly identified transcription products are evidence of important new biochemical pathways or are merely 'junk' RNA generated by the cell as a by-product of its functional activities.

Animals↗
PubMed2004

Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome.

One of the largest families of small RNAs in eukaryotes is the H/ACA small nucleolar RNAs (snoRNAs), most of which guide RNA pseudouridine formation. So far, an effective computational method specifically for identifying H/ACA snoRNA gene sequences has not been established. We have developed snoGPS, a program for computationally screening genomic sequences for H/ACA guide snoRNAs. The program implements a deterministic screening algorithm combined with a probabilistic model to score gene candidates. We report here the results of testing snoGPS on the budding yeast Saccharomyces cerevisiae. Six candidate snoRNAs were verified as novel RNA transcripts, and five of these were verified as guides for pseudouridine formation at specific sites in ribosomal RNA. We also predicted 14 new base-pairings between snoRNAs and known pseudouridine sites in S.cerevisiae rRNA, 12 of which were verified by gene disruption and loss of the cognate pseudouridine site. Our findings include the first prediction and verification of snoRNAs that guide pseudouridine modification at more than two sites. With this work, 41 of the 44 known pseudouridine modifications in S.cerevisiae rRNA have been linked with a verified snoRNA, providing the most complete accounting of the H/ACA snoRNAs that guide pseudouridylation in any species.

Algorithms↗
PubMed2003

Rural secondary school students living in a small community: their attitudes, beliefs and perceptions towards general practice.

OBJECTIVE: To study the attitudes and beliefs towards general practice of rural secondary school students, in particular, their perception of the barriers to the effective delivery of primary health care. SETTING: Students attending a government-funded secondary school in a rural community of less than 4000 people. SUBJECTS: 250 students in years 7-12 were surveyed, with 177 (71%) replying, 45% of these being male. DESIGN: Cross-sectional, self-administered questionnaire survey. RESULTS: The study found that most students value general practitioners (GPs) as valuable sources of health care, feel they have reasonable access to care and in most instances appear to attend appropriately for their health problems. Most felt their doctor would be an empathetic listener, would provide sufficient time to provide effective care and communicated in a language they could understand. Confidentiality issues were considered important, especially by females. CONCLUSION: Although students have very positive attitudes about general practice, the findings could be used to improve a number of GP services for young people in small rural communities. This is particularly so for presentations which require a high degree of confidentiality and skillful counselling, such as psychological problems and risk-taking behaviours.

Adolescent↗
PubMed2002

Searching for RNA genes using base-composition statistics.

The hypothesis that genomic regions rich in non-protein-coding RNAs (ncRNAs) can be identified using local variations in single-base and dinucleotide statistics has been investigated. (G+C)%, (G-C)% difference, (A-T)% difference and dinucleotide-frequency statistics were compared among seven classes of ncRNAs and three genomes. Significant variations were observed in (G+C)% and, in Methanococcus jannaschii, in the frequency of the dinucleotide 'CG'. Screening programs based on these two base-composition statistics were developed. With (G+C)% screening alone, a 1% fraction of the M.jannaschii genome containing all 44 known transfer RNAs, ribosomal RNAs and signal recognition particle RNAs could be identified. When (G+C)% combined with CG dinucleotide-frequency screening was used, 43 of the 44 known M.jannaschii structural ncRNAs were again identified, while the number of presumably false hits overlapping a known or putative protein-coding gene was reduced from 15 to 6. In addition, 19 candidate ncRNAs were identified including one with significant homology to several known archaeal RNaseP RNAs.

Animals↗
PubMed2002

The Bioperl toolkit: Perl modules for the life sciences.

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.

Algorithms↗
PubMedDate not supplied

Audit of a behaviour modification program for weight management.

BACKGROUND: The traditional management of overweight and obesity is to make weight loss the primary goal and to offer advice about eating less and exercising more. In controlled settings participants who remain in weight loss programs usually lose 10% of their weight, However, one to two-thirds of the weight lost is regained within one year, and almost all is regained within five years. METHOD: At the Melbourne Weight Management and Eating Behaviour Clinic we designed a program to assist patients achieve and maintain a healthy weight. The program is based on achieving behaviour change rather than focussing on weight loss as the primary goal. The focus is on the reasons why patients exceed their most healthy weight, setting realistic behaviour change and accepting what cannot be changed. DISCUSSION: We conducted an audit of this program to identify changes in eating behaviour and weight management, and examine whether any change were maintained after the completion of the program.

Behavior Therapy↗
PubMedDate not supplied

Using computers to work smarter--a guide for GPs.

BACKGROUND: Computers have many uses in general practice, but to get the most out of them requires commitment of time and money. OBJECTIVE: This article describes some of the most important benefits of computers, but also indicates some of the difficulties in their use which can be overcome with simple strategies. DISCUSSION: Realising the benefits of computers requires a positive mindset which welcomes their role in improving the quality of patient care and the efficiency of general practice.

Ambulatory Care Information Systems↗