Understanding the language of gene regulation

A report on the Cold Spring Harbor Laboratory meeting 'Systems Biology: genomic approaches to transcriptional regulation', Cold Spring Harbor, USA, 6-9 March 2003

Dentistry handbook

2000 handbook for the faculty of Dentistr

CoPub update: CoPub 5.0 a text mining system to answer biological questions

In this article, we present CoPub 5.0, a publicly available text mining system, which uses Medline abstracts to calculate robust statistics for keyword co-occurrences. CoPub was initially developed for the analysis of microarray data, but we broadened the scope by implementing new technology and new thesauri. In CoPub 5.0, we integrated existing CoPub technology with new features, and provided a new advanced interface, which can be used to answer a variety of biological questions. CoPub 5.0 allows searching for keywords of interest and its relations to curated thesauri and provides highlighting and sorting mechanisms, using its statistics, to retrieve the most important abstracts in which the terms co-occur. It also provides a way to search for indirect relations between genes, drugs, pathways and diseases, following an ABC principle, in which A and C have no direct connection but are connected via shared B intermediates. With CoPub 5.0, it is possible to create, annotate and analyze networks using the layout and highlight options of Cytoscape web, allowing for literature based systems biology. Finally, operations of the CoPub 5.0 Web service enable to implement the CoPub technology in bioinformatics workflows. CoPub 5.0 can be accessed through the CoPub portal http://www.copub.org

The balance of Polo-like kinase 1 in tumorigenesis

Polo-like kinase 1 (Plk1) belongs to a family of conserved serine/threonine kinases with a polo-box domain, which have similar but non-overlapping functions in the cell cycle progression. Plk1 plays a key role to ensure the normal mitosis. Interestingly, overexpression of Plk1 is associated with tumor development and could serve as a prognostic marker for many cancers. Due to Plk1 overexpression, several Plk1 inhibitors have been developed and tested for the cancer treatment. However, in a recent study, it has been suggested that down-regulation of Plk1 could also induce aneuploidy and tumor formation in vivo. Therefore, a normal level of Plk1 is important for mitosis. And caution should be taken when Plk1 inhibitors are used in the clinical trial and their side effects including tumorigenesis should be carefully evaluated

PhyloPat: an updated version of the phylogenetic pattern database contains gene neighborhood

Phylogenetic patterns show the presence or absence of certain genes in a set of full genomes derived from different species. They can also be used to determine sets of genes that occur only in certain evolutionary branches. Previously, we presented a database named PhyloPat which allows the complete Ensembl gene database to be queried using phylogenetic patterns. Here, we describe an updated version of PhyloPat which can be queried by an improved web server. We used a single linkage clustering algorithm to create 241 697 phylogenetic lineages, using all the orthologies provided by Ensembl v49. PhyloPat offers the possibility of querying with binary phylogenetic patterns or regular expressions, or through a phylogenetic tree of the 39 included species. Users can also input a list of Ensembl, EMBL, EntrezGene or HGNC IDs to check which phylogenetic lineage any gene belongs to. A link to the FatiGO web interface has been incorporated in the HTML output. For each gene, the surrounding genes on the chromosome, color coded according to their phylogenetic lineage can be viewed, as well as FASTA files of the peptide sequences of each lineage. Furthermore, lists of omnipresent, polypresent, oligopresent and anticorrelating genes have been included. PhyloPat is freely available at http://www.cmbi.ru.nl/phylopat

Estimating the Under-Five Mortality Rate Using a Bayesian Hierarchical Time Series Model

Background: Millennium Development Goal 4 calls for a reduction in the under-five mortality rate by two-thirds between 1990 and 2015, which corresponds to an annual rate of decline of 4.4%. The United Nations Inter-Agency Group for Child Mortality Estimation estimates under-five mortality in every country to measure progress. For the majority of countries, the estimates within a country are based on the assumption of a piece-wise constant rate of decline. Methods and Findings: This paper proposes an alternative method to estimate under-five mortality, such that the underlying rate of change is allowed to vary smoothly over time using a time series model. Information about the average rate of decline and changes therein is exchanged between countries using a Bayesian hierarchical model. Cross-validation exercises suggest that the proposed model provides credible bounds for the under-five mortality rate that are reasonably well calibrated during the observation period. The alternative estimates suggest smoother trends in under-five mortality and give new insights into changes in the rate of decline within countries. Conclusions: The proposed model offers an alternative modeling approach for obtaining estimates of under-five mortality which removes the restriction of a piece-wise linear rate of decline and introduces hierarchy to exchange information between countries. The newly proposed estimates of the rate of decline in under-5 mortality and the uncertaint

Investigating the impact of poverty on mental illness in the UK Biobank using Mendelian Randomization

It is unclear whether poverty and mental illness are causally related. Using UK Biobank and Psychiatric Genomic Consortium data, we examined evidence of causal links between poverty and nine mental illnesses (attention deficit and hyperactivity disorder (ADHD), anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia). We applied genomic structural equation modelling to derive a poverty common factor from household income, occupational income and social deprivation. Then, using Mendelian randomization, we found evidence that schizophrenia and ADHD causally contribute to poverty, while poverty contributes to major depressive disorder and schizophrenia but decreases the risk of anorexia nervosa. Poverty may also contribute to ADHD, albeit with uncertainty due to unbalanced pleiotropy. The effects of poverty were reduced by approximately 30% when we adjusted for cognitive ability. Further investigations of the bidirectional relationships between poverty and mental illness are warranted, as they may inform efforts to improve mental health for all

Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment

The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here, we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses associated with reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e. transmission investment) and reduced growth (i.e. asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission

Magnetic Resonance Imaging-targeted Prostate Biopsy Compared with Systematic Prostate Biopsy in Biopsy-naïve Patients with Suspected Prostate Cancer

BACKGROUND: It remains uncertain whether transrectal ultrasound (TRUS)-guided systematic biopsies can be omitted and rely solely on multiparametric magnetic resonance imaging–targeted biopsies (MRI-TBx) in biopsy-naïve men suspected of prostate cancer (PCa). OBJECTIVE: To compare PCa detection in biopsy-naïve men between systematic biopsy and MRI-TBx. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in a Dutch teaching hospital. Consecutive patients with suspected PCa, no history of biopsy, and no clinical suspicion of metastasis underwent both TRUS-guided systematic biopsies and MRI-TBx by multiparametric magnetic resonance imaging (mpMRI)-ultrasound fusion, including sham biopsies in case of negative mpMRI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinically significant PCa (csPCa), defined as group ≥2 on the International Society of Urological Pathology grading, was detected. RESULTS AND LIMITATIONS: The overall prevalence of csPCa, irrespective of biopsy technique, was 37.4% (132/353) in our population. MRI-TBx were performed in 263/353 (74.5%) patients with suspicious mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The detection rates for csPCa were 39.5% for MRI-TBx and 42.9% for systematic biopsies. The added values, defined as the additional percentages of patients with csPCa detected by adding one biopsy technique, were 8.7% for the systematic biopsies and 5.3% for MRI-TBx. In patients with nonsuspicious mpMRI, five cases (6%) of csPCa were found by systematic biopsies. CONCLUSIONS: This study in biopsy-naïve patients suspected for PCa showed that systematic biopsies have added value to MRI-TBx alone in patients with mpMRI PI-RADS >2. PATIENT SUMMARY: We studied magnetic resonance imaging (MRI)-guided prostate biopsy for diagnosing prostate cancer and compared it with the standard method of prostate biopsy. Standard systematic biopsies cannot be omitted in patients with suspicious MRI, as they add to the detection of significant prostate cancer

Rapid Scaling Up of Insecticide-Treated Bed Net Coverage in Africa and Its Relationship with Development Assistance for Health: A Systematic Synthesis of Supply, Distribution, and Household Survey Data

Stephen Lim and colleagues use several sources of data to estimate the changes in distribution of insecticide-treated bed nets across Africa between 2000 and 2008, and to analyze the link between development assistance and net coverage