Use of genomic DNA control features and predicted operon structure in microarray data analysis: ArrayLeaRNA – a Bayesian approach

<p>Abstract</p> <p>Background</p> <p>Microarrays are widely used for the study of gene expression; however deciding on whether observed differences in expression are significant remains a challenge.</p> <p>Results</p> <p>A computing tool (ArrayLeaRNA) has been developed for gene expression analysis. It implements a Bayesian approach which is based on the Gumbel distribution and uses printed genomic DNA control features for normalization and for estimation of the parameters of the Bayesian model and prior knowledge from predicted operon structure. The method is compared with two other approaches: the classical LOWESS normalization followed by a two fold cut-off criterion and the OpWise method (Price, et al. 2006. BMC Bioinformatics. 7, 19), a published Bayesian approach also using predicted operon structure. The three methods were compared on experimental datasets with prior knowledge of gene expression. With ArrayLeaRNA, data normalization is carried out according to the genomic features which reflect the results of equally transcribed genes; also the statistical significance of the difference in expression is based on the variability of the equally transcribed genes. The operon information helps the classification of genes with low confidence measurements.</p> <p>ArrayLeaRNA is implemented in Visual Basic and freely available as an Excel add-in at <url>http://www.ifr.ac.uk/safety/ArrayLeaRNA/</url></p> <p>Conclusion</p> <p>We have introduced a novel Bayesian model and demonstrated that it is a robust method for analysing microarray expression profiles. ArrayLeaRNA showed a considerable improvement in data normalization, in the estimation of the experimental variability intrinsic to each hybridization and in the establishment of a clear boundary between non-changing and differentially expressed genes. The method is applicable to data derived from hybridizations of labelled cDNA samples as well as from hybridizations of labelled cDNA with genomic DNA and can be used for the analysis of datasets where differentially regulated genes predominate.</p

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

LeMMINGs - II. The e-MERLIN legacy survey of nearby galaxies. The deepest radio view of the Palomar sample on parsec scale

We present the second data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 177 nearby galaxies from the Palomar sample, observed with the e-MERLIN array, as part of the Legacy e-MERLIN Multi-band Imaging of Nearby Galaxies Sample (LeMMINGs) survey. Together with the 103 targets of the first LeMMINGs data release, this represents a complete sample of 280 local active (LINER and Seyfert) and inactive galaxies (H II galaxies and absorption line galaxies, ALG). This large program is the deepest radio survey of the local Universe, ≳1017.6 W Hz−1, regardless of the host and nuclear type: we detect radio emission ≳0.25 mJy beam−1 for 125/280 galaxies (44.6 per cent) with sizes of typically ≲100 pc. Of those 125, 106 targets show a core which coincides within 1.2 arcsec with the optical nucleus. Although we observed mostly cores, around one third of the detected galaxies features jetted morphologies. The detected radio core luminosities of the sample range between ∼1034 and 1040 erg s−1. LINERs and Seyferts are the most luminous sources, whereas H II galaxies are the least. LINERs show FR I-like core-brightened radio structures while Seyferts reveal the highest fraction of symmetric morphologies. The majority of H II galaxies have single radio core or complex extended structures, which probably conceal a nuclear starburst and/or a weak active nucleus (seven of them show clear jets). ALGs, which are typically found in evolved ellipticals, although the least numerous, exhibit on average the most luminous radio structures, similar to LINERs

Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection

LeMMINGs III. The e-MERLIN legacy survey of the Palomar sample: exploring the origin of nuclear radio emission in active and inactive galaxies through the [O iii] – radio connection

What determines the nuclear radio emission in local galaxies? To address this question, we combine optical [O III] line emission, robust black hole (BH) mass estimates, and high-resolution e-MERLIN 1.5-GHz data, from the LeMMINGs survey, of a statistically complete sample of 280 nearby optically active (LINER and Seyfert) and inactive [H II and absorption line galaxies (ALGs)] galaxies. Using [O III] luminosity (⁠L[OIII]⁠) as a proxy for the accretion power, local galaxies follow distinct sequences in the optical–radio planes of BH activity, which suggest different origins of the nuclear radio emission for the optical classes. The 1.5-GHz radio luminosity of their parsec-scale cores (Lcore) is found to scale with BH mass (MBH) and [O III] luminosity. Below MBH ∼ 106.5 M⊙, stellar processes from non-jetted H II galaxies dominate with Lcore∝M0.61±0.33BH and Lcore∝L0.79±0.30[OIII]⁠. Above MBH ∼ 106.5 M⊙, accretion-driven processes dominate with Lcore∝M1.5−1.65BH and Lcore∝L0.99−1.31[OIII] for active galaxies: radio-quiet/loud LINERs, Seyferts, and jetted H II galaxies always display (although low) signatures of radio-emitting BH activity, with L1.5GHz≳1019.8 W Hz−1 and MBH ≳ 107 M⊙, on a broad range of Eddington-scaled accretion rates (⁠m˙⁠). Radio-quiet and radio-loud LINERs are powered by low-m˙ discs launching sub-relativistic and relativistic jets, respectively. Low-power slow jets and disc/corona winds from moderately high to high-m˙ discs account for the compact and edge-brightened jets of Seyferts, respectively. Jetted H II galaxies may host weakly active BHs. Fuel-starved BHs and recurrent activity account for ALG properties. In conclusion, specific accretion–ejection states of active BHs determine the radio production and the optical classification of local active galaxies

Ranking differentially expressed genes from Affymetrix gene expression data: methods with reproducibility, sensitivity, and specificity

<p>Abstract</p> <p>Background</p> <p>To identify differentially expressed genes (DEGs) from microarray data, users of the Affymetrix GeneChip system need to select both a preprocessing algorithm to obtain expression-level measurements and a way of ranking genes to obtain the most plausible candidates. We recently recommended suitable combinations of a preprocessing algorithm and gene ranking method that can be used to identify DEGs with a higher level of sensitivity and specificity. However, in addition to these recommendations, researchers also want to know which combinations enhance reproducibility.</p> <p>Results</p> <p>We compared eight conventional methods for ranking genes: weighted average difference (WAD), average difference (AD), fold change (FC), rank products (RP), moderated <it>t </it>statistic (modT), significance analysis of microarrays (samT), shrinkage <it>t </it>statistic (shrinkT), and intensity-based moderated <it>t </it>statistic (ibmT) with six preprocessing algorithms (PLIER, VSN, FARMS, multi-mgMOS (mmgMOS), MBEI, and GCRMA). A total of 36 real experimental datasets was evaluated on the basis of the area under the receiver operating characteristic curve (AUC) as a measure for both sensitivity and specificity. We found that the RP method performed well for VSN-, FARMS-, MBEI-, and GCRMA-preprocessed data, and the WAD method performed well for mmgMOS-preprocessed data. Our analysis of the MicroArray Quality Control (MAQC) project's datasets showed that the FC-based gene ranking methods (WAD, AD, FC, and RP) had a higher level of reproducibility: The percentages of overlapping genes (POGs) across different sites for the FC-based methods were higher overall than those for the <it>t</it>-statistic-based methods (modT, samT, shrinkT, and ibmT). In particular, POG values for WAD were the highest overall among the FC-based methods irrespective of the choice of preprocessing algorithm.</p> <p>Conclusion</p> <p>Our results demonstrate that to increase sensitivity, specificity, and reproducibility in microarray analyses, we need to select suitable combinations of preprocessing algorithms and gene ranking methods. We recommend the use of FC-based methods, in particular RP or WAD.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

PathEx: a novel multi factors based datasets selector web tool

<p>Abstract</p> <p>Background</p> <p>Microarray experiments have become very popular in life science research. However, if such experiments are only considered independently, the possibilities for analysis and interpretation of many life science phenomena are reduced. The accumulation of publicly available data provides biomedical researchers with a valuable opportunity to either discover new phenomena or improve the interpretation and validation of other phenomena that partially understood or well known. This can only be achieved by intelligently exploiting this rich mine of information.</p> <p>Description</p> <p>Considering that technologies like microarrays remain prohibitively expensive for researchers with limited means to order their own experimental chips, it would be beneficial to re-use previously published microarray data. For certain researchers interested in finding gene groups (requiring many replicates), there is a great need for tools to help them to select appropriate datasets for analysis. These tools may be effective, if and only if, they are able to re-use previously deposited experiments or to create new experiments not initially envisioned by the depositors. However, the generation of new experiments requires that all published microarray data be completely annotated, which is not currently the case. Thus, we propose the PathEx approach.</p> <p>Conclusion</p> <p>This paper presents PathEx, a human-focused web solution built around a two-component system: one database component, enriched with relevant biological information (expression array, omics data, literature) from different sources, and another component comprising sophisticated web interfaces that allow users to perform complex dataset building queries on the contents integrated into the PathEx database.</p

LeMMINGs. VI. Connecting nuclear activity to bulge properties of active and inactive galaxies: radio scaling relations and galaxy environment

Multiwavelength studies indicate that nuclear activity and bulge properties are closely related, but the details remain unclear. To study this further, we combine Hubble Space Telescope bulge structural and photometric properties with 1.5 GHz, e-MERLIN nuclear radio continuum data from the LeMMINGs survey for a large sample of 173 'active' galaxies (LINERs and Seyferts) and 'inactive' galaxies (H IIs and absorption line galaxies, ALGs). Dividing our sample into active and inactive, they define distinct (radio core luminosity)-(bulge mass), LR,core − M∗,bulge, relations, with a mass turnover at M∗,bulge ∼ 109.8±0.3M☉ (supermassive blackhole mass MBH ∼ 106.8±0.3M☉), which marks the transition from AGN-dominated nuclear radio emission in more massive bulges to that mainly driven by stellar processes in low-mass bulges. None of our 10/173 bulge-less galaxies host an AGN. The AGN fraction increases with increasing M∗,bulge such that foptical_AGN ∝ M∗,bulge0.24±0.06 and fradio_AGN ∝ M∗,bulge0.24±0.05. Between M∗,bulge ∼ 108.5 and 1011.3M☉, foptical_AGN steadily rises from 15 ± 4 to 80 ± 5 per cent. We find that at fixed bulge mass, the radio loudness, nuclear radio activity, and the (optical and radio) AGN fraction exhibit no dependence on environment. Radio-loud hosts preferentially possess an early-type morphology than radio-quiet hosts, the two types are however indistinguishable in terms of bulge Sérsic index and ellipticity, while results on the bulge inner logarithmic profile slope are inconclusive. We finally discuss the importance of bulge mass in determining the AGN triggering processes, including potential implications for the nuclear radio emission in nearby galaxies