CoryneCenter – An online resource for the integrated analysis of corynebacterial genome and transcriptome data

Neuweger H, Baumbach J, Albaum S, et al. CoryneCenter: an online resource for the integrated analysis of corynebacterial genome and transcriptome data. BMC Systems Biology. 2007;1(1): 55.Background: The introduction of high-throughput genome sequencing and post-genome analysis technologies, e.g. DNA microarray approaches, has created the potential to unravel and scrutinize complex gene-regulatory networks on a large scale. The discovery of transcriptional regulatory interactions has become a major topic in modern functional genomics. Results: To facilitate the analysis of gene-regulatory networks, we have developed CoryneCenter, a web-based resource for the systematic integration and analysis of genome, transcriptome, and gene regulatory information for prokaryotes, especially corynebacteria. For this purpose, we extended and combined the following systems into a common platform: (1) GenDB, an open source genome annotation system, (2) EMMA, a MAGE compliant application for high-throughput transcriptome data storage and analysis, and (3) CoryneRegNet, an ontology-based data warehouse designed to facilitate the reconstruction and analysis of gene regulatory interactions. We demonstrate the potential of CoryneCenter by means of an application example. Using microarray hybridization data, we compare the gene expression of Corynebacterium glutamicum under acetate and glucose feeding conditions: Known regulatory networks are confirmed, but moreover CoryneCenter points out additional regulatory interactions. Conclusion: CoryneCenter provides more than the sum of its parts. Its novel analysis and visualization features significantly simplify the process of obtaining new biological insights into complex regulatory systems. Although the platform currently focusses on corynebacteria, the integrated tools are by no means restricted to these species, and the presented approach offers a general strategy for the analysis and verification of gene regulatory networks. CoryneCenter provides freely accessible projects with the underlying genome annotation, gene expression, and gene regulation data. The system is publicly available at http://www.CoryneCenter.d

CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

Background: The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. // Results: Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. // Conclusions: Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A reference map of the human binary protein interactome.

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes

MoRAine - A web server for fast computational transcription factor binding motif re-annotation

Background: A precise experimental identification of transcription factor binding motifs (TFBMs), accurate to a single base pair, is time-consuming and difficult. For several databases, TFBM annotations are extracted from the literature and stored 5ʹ → 3ʹ relative to the target gene. Mixing the two possible orientations of a motif results in poor information content of subsequently computed position frequency matrices (PFMs) and sequence logos. Since these PFMs are used to predict further TFBMs, we address the question if the TFBMs underlying a PFM can be re-annotated automatically to improve both the information content of the PFM and subsequent classification performance

Treatment of Tularemia in Patient with Chronic Graft-versus-Host Disease

We describe a case of human tularemia caused by Francisella tularensis subsp. holarctica in a stem cell transplant recipient with chronic graft-versus-host disease who was receiving levofloxacin prophylaxis. The infection was characterized by pneumonia with septic complications. The patient was successfully treated with doxycycline. Tularemia is a zoonotic infection caused by the gramnegative bacterium Francisella tularensis. Humans are accidental hosts; infection occurs after contact with infected animals, contaminated water or soil, or invertebrate vectors (1). Strains of the 2 subspecies F. tularensis subsp. tularensis and F. tularensis subsp. holarctica account for virtually all infections in humans. Only rarely have strains of the subspecies F. tularensis novicida or the closely related species F. philomiragia or F. hispaniensis been cultured from clinical specimens (2). F. tularensis subsp. tularensis, also referred to as type A, is found almost exclusively in North America and is the most virulent subspecies. F. tularensis subsp. holarctica, also referred to as type B, is found predominantly in Asia and Europe, but also in North America (3). Patients infected with F. tularensis have abrupt onset of fever, chills, headache, and malaise after an incubation period of 2–21 days. Additional signs and symptoms may develop, depending on the portal of entry. The most common signs and symptoms are lymphadenopathy, fever, pharyngitis, appearance of ulcers/eschars/papules, nausea and vomiting, and hepatosplenomegaly. Antimicrobial drug therapy should be administered to patients with this suspected or confirmed diagnosis, even though spontaneous resolution may occur in 50%–95 % o

The early use of appropriate prophylactic antibiotics in susceptible women for the prevention of preterm birth of infectious etiology

INTRODUCTION: Preterm birth is the major cause of perinatal mortality and morbidity in high-income countries. The etiology of preterm birth is multifactorial but there is overwhelming evidence to implicate infection as a major cause. Abnormal genital tract flora in early pregnancy is predictive of preterm birth so it is logical to consider the use of antibiotics for the prevention of preterm birth.AREAS COVERED: Infection and antibiotics in the etiology, prediction and prevention of preterm birth.EXPERT OPINION: Antibiotics for the prevention of preterm birth have addressed different risk groups, diagnostic methods, degrees of abnormal flora, antibiotic dose regimens, routes of administration, host susceptibilities, host response, gestational age at time of treatment, outcome parameters and definitions of success and outcomes. To address this confusion, a number of systematic reviews/meta-analyses have been conducted but none has simultaneously addressed the optimal choice of agent, patient and timing of intervention. We conclude that inappropriate antibiotics used in inappropriate women at inappropriately late gestations do not reduce preterm birth. Conversely, a focused systematic review/meta-analysis, which targeted the use of clindamycin before 22 weeks gestation, in women with objective evidence of abnormal genital tract flora, demonstrated that clindamycin produced a significant decrease in late miscarriage and preterm birth.</p

MoRAine - A web server for fast computational transcription factor binding motif re-annotation

SummaryBackground: A precise experimental identification of transcription factor binding motifs (TFBMs), accurate to a single base pair, is time-consuming and difficult. For several databases, TFBM annotations are extracted from the literature and stored 5ʹ → 3ʹ relative to the target gene. Mixing the two possible orientations of a motif results in poor information content of subsequently computed position frequency matrices (PFMs) and sequence logos. Since these PFMs are used to predict further TFBMs, we address the question if the TFBMs underlying a PFM can be re-annotated automatically to improve both the information content of the PFM and subsequent classification performance.Results: We present MoRAine, an algorithm that re-annotates transcription factor binding motifs. Each motif with experimental evidence underlying a PFM is compared against each other such motif. The goal is to re-annotate TFBMs by possibly switching their strands and shifting them a few positions in order to maximize the information content of the resulting adjusted PFM. We present two heuristic strategies to perform this optimization and subsequently show that MoRAine significantly improves the corresponding sequence logos. Furthermore, we justify the method by evaluating specificity, sensitivity, true positive, and false positive rates of PFM-based TFBM predictions for E. coli using the original database motifs and the MoRAine-adjusted motifs. The classification performance is considerably increased if MoRAine is used as a preprocessing step.Conclusions: MoRAine is integrated into a publicly available web server and can be used online or downloaded as a stand-alone version from http://moraine.cebitec.uni-bielefeld.de.</jats:p