Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests

Scintillation Materials for Medical Applications

Scintillators are beginning to attract renewed attention because modern High Energy Physics accelerators are placing unprecedented demands of quantity and quality of detector materials and Positron Emission Tomography (PET), used by the medical field. Both applications required materials for scintillator detectors with properties beyond those delivered by traditional scintillators. Thallium doped halides are very efficient, but slow and chemically unstable. Two modern developments, namely the very fast BaF[sub 2], which owed its success to the newly discovered crossover transitions, and CeF[sub 3], which carried a promise of fast components, more practical wavelengths and attractive efficiency. Since traditional scintillators (Tl doped halides) are very efficient, and could be even more efficient at larger concentrations of Tl, if it were not for concentration quenching. However Tl transitions are spin forbidden and slow. Both ills could be remedied by replacing Tl with Ce, whose transitions are allowed and which is known to form fully concentrated compounds of high photoluminescent efficiency and no quenching. These materials, plus new Ce-doped materials, exhibiting highly promising properties for medical applications, became the target of our studies

Gene duplications in prokaryotes can be associated with environmental adaptation

<p>Abstract</p> <p>Background</p> <p>Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes.</p> <p>Results</p> <p>Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis.</p> <p>Conclusions</p> <p>Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive advantage to the organism. Paralogs and singletons dominate different categories of functional classification, where paralogs in particular seem to be associated with processes involving interaction with the environment.</p

Transcriptomic response to differentiation induction

BACKGROUND: Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. METHODS: We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL) are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome. RESULTS: Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements). We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by drug treatment. CONCLUSION: Improvement is needed in understanding the nature of the mutations responsible for controlling the maturation process and how these genes regulate downstream effects if there is to be better targeting of chemical interventions. Expanded implementation of the techniques and results reported here may better direct future efforts to improve treatment for diseases not restricted to APL

PubMatrix: a tool for multiplex literature mining

BACKGROUND: Molecular experiments using multiplex strategies such as cDNA microarrays or proteomic approaches generate large datasets requiring biological interpretation. Text based data mining tools have recently been developed to query large biological datasets of this type of data. PubMatrix is a web-based tool that allows simple text based mining of the NCBI literature search service PubMed using any two lists of keywords terms, resulting in a frequency matrix of term co-occurrence. RESULTS: For example, a simple term selection procedure allows automatic pair-wise comparisons of approximately 1–100 search terms versus approximately 1–10 modifier terms, resulting in up to 1,000 pair wise comparisons. The matrix table of pair-wise comparisons can then be surveyed, queried individually, and archived. Lists of keywords can include any terms currently capable of being searched in PubMed. In the context of cDNA microarray studies, this may be used for the annotation of gene lists from clusters of genes that are expressed coordinately. An associated PubMatrix public archive provides previous searches using common useful lists of keyword terms. CONCLUSIONS: In this way, lists of terms, such as gene names, or functional assignments can be assigned genetic, biological, or clinical relevance in a rapid flexible systematic fashion

Interferon stimulated exonuclease gene 20 kDa links psychiatric events to distinct hepatitis C virus responses in human immunodeficiency virus positive patients: ISG20 Links Psychiatric Events to HCV Clearance

Hepatitis C Virus (HCV) infection occurs frequently in patients with preexisting mental illness. Treatment for chronic hepatitis C using interferon formulations often increases risk for neuropsychiatric symptoms. Pegylated-Interferon-α (PegIFN-α) remains crucial for attaining sustained virologic response (SVR); however, PegIFN-α based treatment is associated with psychiatric adverse effects, which require dose reduction and/or interruption. This study's main objective was to identify genes induced by PegIFN-α and expressed in the central nervous system and immune system, which could mediate the development of psychiatric toxicity in association with antiviral outcome. Using peripheral blood mononuclear cells from Human Immunodeficiency Virus (HIV)/HCV co-infected donors (N=28), DNA microarray analysis was performed and 21 differentially regulated genes were identified in patients with psychiatric toxicity vs. those without. Using these 21 expression profiles a two-way-ANOVA was performed to select genes based on antiviral outcome and occurrence of neuropsychiatric adverse events. Microarray analysis demonstrated that Interferon-stimulated-exonuclease-gene 20kDa (ISG20) and Interferon-alpha-inducible-protein 27 (IFI27) were the most regulated genes (P<0.05) between three groups that were built by combining antiviral outcome and neuropsychiatric toxicity. Validation by bDNA assay confirmed that ISG20 expression levels were significantly associated with these outcomes (P<0.035). Baseline levels and induction of ISG20 correlated independently with no occurrence of psychiatric adverse events and non-response to therapy (P<0.001). Among the 21 genes that were associated with psychiatric adverse events and 20 Interferon-inducible genes (IFIGs) used as controls, only ISG20 expression was able to link PegIFN-α related neuropsychiatric toxicity to distinct HCV-responses in patients co-infected with HIV and HCV in vivo

Cerium Compounds as Scintillators

Stoichiometric Ce-materials with negligible Ce-Ce interactions should have superior scintillator properties. We present two materials: CeF{sub 3} and Ce{sub x}La{sub 1-x}P{sub 5}O{sub 14}. While cerium trifluoride is a known scintillator, pentaphosphate is of a limited usefulness, except as a remarkable model material. We show that quenching in fluoride is responsible for loss of 50% of the light output and is the cause of the, so-called, ultra fast component (2 ns). Light output of fluoride (about 50% of BGO) could be significantly improved. Deeper understanding of Ce-systems is needed to fully exploit their potentials. 10 figs., 6 refs