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Comparative genome hybridization of Streptococcus mutans strains (vol 22, pg 103, 2007)

ORAL MICROBIOLOGY AND IMMUNOLOGY 2007年第3期22卷 216-216页

作者： Waterhouse, J. C. Swan, D. C. Russell, R. R. B. Oral Biology School of Dental Sciences Bioinformatics Support Unit Newcastle University Newcastle upon Tyne UK

The basis for genotypic and phenotypic variation within Streptococcus mutans is poorly understood but the availability of the genome sequence of strain UA159 provides an opportunity for comparative studies. Genomic DNA prepared from nine strains of S. mutans was used to probe a microarray consisting of oligonucleotides representing 1948 open reading frames of S. mutans UA159. A total of 385 (20%) of the UA159 open reading frames were found to be absent from one or more of the test strains. Absent open reading frames frequently occurred in blocks of adjacent open reading frames and represented regions previously experimentally detected by polymerase chain reaction, predicted genomic islands and insertion sequence elements as well as novel open reading frames. Approximately half appear to involve foreign DNA acquired by horizontal transmission. The results indicate the existence of distinct core and dispensable genomes and may help explain the phenotypic and genotypic variation within S. mutans.

关键词： genome microarray Streptococcus mutans

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Spectral flow cytometry for detecting DNA cargo in malaria parasite–derived extracellular vesicles

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Journal of Biological Chemistry 2025年第5期301卷 108481页

作者： Kozela, Ewa Petrovich-Kopitman, Ekaterina Berger, Yuval Camacho, Abel Cruz Shoham, Yaara Morandi, Mattia I. Rosenhek-Goldian, Irit Rotkopf, Ron Regev-Rudzki, Neta Department of Biomolecular Sciences Faculty of Biochemistry Weizmann Institute of Science Rehovot Israel Flow Cytometry Unit Life Sciences Core Facilities Weizmann Institute of Science Rehovot Israel Institute of Organic Chemistry and Biochemistry of the Czech Academy of Science Prague Czech Republic The International Institute of Molecular Mechanisms and Machines Polish Academy of Sciences Warsaw Poland Department of Chemical Research Support Weizmann Institute of Science Rehovot Israel Bioinformatics Unit Life Science Core Facilities Weizmann Institute of Science Rehovot Israel

Cells across biological kingdoms release extracellular vesicles (EVs) as a means of communication with other cells, be their friends or foes. This is indeed true for the intracellular malaria parasite Plasmodium falciparum (Pf), which utilizes EVs to transport bioactive molecules to various human host systems. Yet, the study of this mode of communication in malaria research is currently constrained due to limitations in high-resolution tools and the absence of commercial antibodies. Here, we demonstrate the power of an advanced spectral flow cytometry approach to robustly detect secreted EVs, isolated from Pf-infected red blood cells. By labeling both EV membrane lipids and the DNA cargo within (non-antibody staining approach), we were able to detect a subpopulation of parasitic-derived EVs enriched in DNA. Furthermore, we could quantitatively measure the DNA-carrying EVs isolated from two distinct blood stages of the parasite: rings and trophozoites. Our findings showcase the potential of spectral flow cytometry to monitor dynamic changes in nucleic acid cargo within pathogenic EVs. © 2025 The Authors

关键词： Blood

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GeneAnnot: interfacing GeneCards with high-throughput gene expression compendia.

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Briefings in bioinformatics 2003年第4期4卷 349-360页

作者： Chalifa-Caspi, Vered Shmueli, Orit Benjamin-Rodrig, Hila Rosen, Naomi Shmoish, Michael Yanai, Itai Ophir, Ron Kats, Pavel Safran, Marilyn Lancet, Doron Bioinformatics Support Unit Life Sciences Dept. Ben-Gurion University of the Negev Beer-Sheva Israel

The interpretation of microarray expression results often includes extensive efforts to identify and annotate the gene representatives immobilised on the arrays. In this paper we describe the usage of our automatic GeneAnnot system, which links between Affymetrix arrays and the rich human gene annotations available in GeneCards. We explain GeneCards search options and results display;elaborate on the presentation of expression information in GeneCards, including both our whole-genome GeneNote project and external expression resources;describe the various parameters and displays used by GeneAnnot to assess the annotation quality and probeset specificity;and show how to search GeneAnnot and GeneNote websites directly.

关键词： DNA arrays gene annotation human genome databases

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The Use of EQ-5D in the Middle East and North Africa Region: A Systematic Literature Review

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PharmacoEconomics 2025年 1-19页

作者： Al Rabayah, Abeer Puntscher, Sibylle Al Sayah, Fatima Sawalha, Razan Stolk, Elly Simon, Judit Drummond, Michael Siebert, Uwe Institute of Public Health Medical Decision Making and Health Technology Assessment Department of Public Health Health Services Research and Health Technology Assessment UMIT TIROL-University for Health Sciences and Technology Hall in Tirol Austria Pharmacy Department Center for Drug Policy and Technology Assessment King Hussein Cancer Center Amman Jordan Alberta PROMs & EQ-5D Research & Support Unit (APERSU) School of Public Health University of Alberta Edmonton AB Canada EuroQol Research Foundation Rotterdam Netherlands Erasmus School of Health Policy & Management Erasmus University Rotterdam Rotterdam Netherlands Department of Health Economics Center for Public Health Medical University of Vienna Vienna Austria Department of Psychiatry University of Oxford Oxford United Kingdom Department of Health Policy Institute of Social and Political Sciences Corvinus University Budapest Hungary Centre for Health Economics University of York York United Kingdom Division of Health Technology Assessment and Bioinformatics ONCOTYROL-Center for Personalized Cancer Medicine Innsbruck Austria Departments of Epidemiology and Health Policy and Management Center for Health Decision Science Harvard T.H. Chan School of Public Health Boston MA United States Institute for Technology Assessment and Department of Radiology Massachusetts General Hospital Harvard Medical School Boston MA United States

Introduction: The EQ-5D is the most commonly used preference-based measure of health-related quality of life. There is limited evidence about the use of the EQ-5D in the Middle East and North Africa (MENA) region. This study aimed to systematically identify, review, summarize, and synthesize the published literature on using the EQ-5D in this region. Methods: A systematic literature review was conducted, according to the PRISMA 2020 guidelines, using PubMed, Cochrane, PsycINFO, and CINAHL and covering the period up to 30 August 2024. Studies using any version of the EQ-5D in adults or youth in the MENA region were included. Pilot studies, guidelines, study protocols, and reviews were excluded. Key study characteristics and outcomes assessed included study design, clinical area, population, type of EQ-5D data reported, reference value set used, and mode of administration. Title/abstract screening was conducted independently by two reviewers to assess eligibility for inclusion. Two researchers completed full-text screening and extracted data using a standardized form. Disagreements were referred to a third reviewer if not resolved by discussion. Results were summarized in systematic evidence tables. Results: After removing duplicates, 18,034 references were considered for title/abstract screening. In total, 184 studies were included with a total sample size of 128,164 subjects. Of the included single-country studies, 42% were reported in Iran, 20% in Saudi Arabia, and 11% in Jordan. Patient populations were investigated in 86% of the studies, 23% of which targeted endocrine diseases. Study design was observational in 57% and experimental in 14% of the studies. Only 10% of the included studies applied the EQ-5D in an economic evaluation. The EQ-5D-3L version was used in 40% of the studies. However, the trend is towards a greater use of the 5L version in more recent years. Twenty percent of the studies reported EQ-5D results using the index score, frequencies of severit

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Screening of candidate analgesics using a patient-derived human iPSC model of nociception identifies putative compounds for therapeutic treatment

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Clinical and Translational Medicine 2025年第5期15卷 e70339页

作者： Jack R. Thornton Alberto Capurro Sally Harwood Thomas C Henderson Adrienne Unsworth Franziska Görtler Sushma Nagaraja-Grellscheid Vsevolod Telezhkin Majlinda Lako Evelyne Sernagor Lyle Armstrong Biosciences Institute Newcastle University Newcastle-upon-Tyne UK Bioinformatics Support Unit Newcastle University Newcastle-upon-Tyne UK Department of Biological Sciences University of Bergen Bergen Norway School of Dental Sciences Newcastle University Newcastle-upon-Tyne UK Prof. Evelyne Sernagor passed away during the revision of this manuscript. This work is published in her memory.

Background and purpose In this study, we applied an induced pluripotent stem cell (iPSC)-based model of inherited erythromelalgia (IEM) to screen a library of 281 small molecules, aiming to identify candidate pain-modulating compounds. Experimental approach Human iPSC-derived sensory neuron-like cells, which exhibit action potentials in response to noxious stimulation, were evaluated using whole-cell patch-clamp and microelectrode array (MEA) techniques. Key results Sensory neuron-like cells derived from individuals with IEM showed spontaneous electrical activity characteristic of genetic pain disorders. The drug screen identified four compounds (AZ106, AZ129, AZ037 and AZ237) that significantly decreased spontaneous firing with minimal toxicity. The calculated IC 50 values indicate the potential efficacy of these compounds. Electrophysiological analysis confirmed the compounds’ ability to reduce action potential generation in IEM patient-specific iPSC-derived sensory neuron-like cells. Conclusions and implications Our screening approach demonstrates the reproducibility and effectiveness of human neuronal disease modelling offering a promising avenue for discovering new analgesics. These findings address a critical gap in current therapeutic strategies for both general and neuropathic pain, warranting further investigation. This study highlights the innovative use of patient-derived iPSC sensory neuronal models in pain research and emphasises the potential for personalised medicine in developing targeted analgesics. Key points Utilisation of human iPSCs for efficient differentiation into sensory neuron-like cells offers a novel strategy for studying pain mechanisms. IEM sensory neuron-like cells exhibit key biomarkers and generate action potentials in response to noxious stimulation. IEM sensory neuron-like cells display spontaneous electrical activity, providing a relevant nociceptive model. Screening of 281 compounds identified four candidates that significantly r

关键词： analgesic candidates drug screening electrophysiology induced pluripotent stem cells (iPSCs) inherited erythromelalgia (IEM) sensory neuron

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Clarifying Monastrell red wine with grape seed extracts. Mechanisms of action

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LWT 2025年 226卷

作者： María José Carrasco-Palazón Encarna Gómez-Plaza Paula Pérez-Porras Enrique Pérez-Navarro Ricardo Jurado-Fuentes Ana Belén Bautista-Ortín Department of Food Technology Nutrition and Bromatology Faculty of Veterinary Science. University of Murcia 30100 Murcia Spain Statistical and Bioinformatics Support Unit of the Biosanitary Research Service (SIB) Scientific and Technical Research Area (ACTI). University of Murcia 30100 Murcia Spain Agrovin S.A. Avenida de los Vinos s/n Ciudad Real 13600 Alcázar de San Juan Spain

In winemaking, the clarification stage is crucial to reduce turbidity, so animal-derived protein clarifying agents are commonly used. Nevertheless, these can cause allergic problems and be rejected by vegans. Due to that, plant-based proteins are becoming more popular, although with limited effectiveness. This work studied the behaviour of protein-rich red and white grape seed extracts when applied to a turbid Monastrell red wine, comparing their performance and protein composition with that of different commercial clarifying agents. Results showed that egg albumin and grape seed extracts were similarly effective in reducing wine turbidity after 72 h of contact time. As regard chromatic characteristics, pea protein, white grape seed extract and isinglass significantly reduced the methylcellulose precipitable tannin content, while the anthocyanin concentration was barely affected. Proteomic studies revealed that egg albumin and grape seed extracts present a similar amino acid profile, which may explain their turbidity-reducing effectiveness, indicating that grape seed extracts could be a good alternative to both animal and plant-based clarifying agents.

关键词： Clarifying agents Fining Grape seed extracts Red wine Turbidity Phenolic compounds Amino acids Proteomic

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Interpretable and robust hospital readmission predictions from Electronic Health Records

Interpretable and robust hospital readmission predictions fr...

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2023 IEEE International Conference on Big Data, BigData 2023

作者： Calero-Diaz, Hugo Hamad, Rebeen Ali Atallah, Christian Casement, John Canoy, Dexter Reynolds, Nick J Barnes, Michael Missier, Paolo Newcastle University School of Computing Newcastle upon Tyne United Kingdom Newcastle University Bioinformatics Support Unit Newcastle upon Tyne United Kingdom Newcastle University Faculty of Medical Sciences Newcastle upon Tyne United Kingdom Queen Mary's University of London Centre for Translational Bioinformatics London United Kingdom

ISBN: (纸本)9798350324457

Rates of Hospital Readmission (HR), defined as unplanned readmission within 30 days of discharge, have been increasing over the years, and impose an economic burden on healthcare services worldwide. Despite recent research into predicting HR, few models provide sufficient discriminative ability. Three main drawbacks can be identified in the published literature: (i) imbalance in the target classes (readmitted or not), (ii) not including demographic and lifestyle predictors, and (iii) lack of interpretability of the models. In this work, we address these three points by evaluating class balancing techniques, performing a feature selection process including demographic and lifestyle features, and adding interpretability through a combination of SHapley Additive exPlanations (SHAP) and Accumulated Local Effects (ALE) post hoc methods. Our best classifier for this binary outcome achieves a UAC of 0.849 using a selection of 1296 features, extracted from patients' Electronic Health Records (EHRs) and from their sociodemographics profiles. Using SHAP and ALE, we have established the importance of age, the number of long-term conditions, and the duration of the first admission as top predictors. In addition, we show through an ablation study that demographic and lifestyle features provide even better predictive capabilities than other features, suggesting their relevance toward HR. © 2023 IEEE.

关键词： Classification Feature Selection Hospital readmission Imbalance correction Interpretability

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THU0019 Are micrornas a molecular clock? the newcastle thousand families cohort study

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Annals of the Rheumatic Diseases 2018年 77卷 237-238页

作者： T.L. Jones D.A. Young M.S. Pearce A. Skelton F.N. Birrell Institute of Cellular Medicine Institute of Genetic Medicine Institute of Health and Society Bioinformatics Support Unit Newcastle University Newcastle-upon-Tyne UK

Background No single biomarker has been identified for monitoring ageing trajectory. To date, biological clocks are based on DNA methylation, telomere length, p16 ink4a expression and microsatellite mutations 1 . Body ageing is a complex phenomenon, including a progressive, pro-inflammatory state, termed ‘inflammaging’. MicroRNAs have been linked with cellular senescence and inflammaging. MicroRNAs are short, non-coding sequences of RNA regulating post-transcriptional gene expression with impressive stability and ubiquitous presence, making them ideal candidate biomarkers. Previous studies of circulating microRNAs in ageing were small-scale 2 or compared individuals of different ages, which is methodologically less robust 3 . MicroRNA biomarkers can bring greater understanding to ageing mechanisms, diagnosis/prognosis of age-related disease and even novel treatment targets. Objectives To quantify relationships between circulating microRNA expression and biological ageing and determine whether microRNAs may be a molecular clock. Methods This pilot work is a nested substudy within a prospective, longitudinal birth cohort from May/June 1947 (the Newcastle Thousand Families Study NTFS). Serum samples from 23 subjects taken at ages 50 and 62 years were extracted from the biobank. HTG EdgeSeq microRNA whole transcriptome assay was performed, measuring expression of 2083 human microRNA transcripts using an array followed by next generation sequencing. Global microRNA expression profiles were generated and analysed using this technology, profiling all known microRNAs from a small volume of serum (<15 µL). NIHR funding has been secured for whole cohort analysis. Results Resulting data has shown very strong associations (up to p<10–1 2 ) for biological ageing, with 84 microRNAs meeting p-values<0.05 (see heat map). Analysing the whole cohort will independently validate and extend the findings, in order to identify an ageing signature; the molecular clock. Download: Download h

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Tracking trajectories of multiple long-term conditions using dynamic patient-cluster associations

Tracking trajectories of multiple long-term conditions using...

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2022 IEEE International Conference on Big Data, Big Data 2022

作者： Kremer, Ron Raza, Syed Mohib Eto, Fabiola Casement, John Atallah, Christian Finer, Sarah Lendrem, Dennis Barnes, Michael Reynolds, Nick J Missier, Paolo Newcastle University School of Computing Newcastle upon Tyne United Kingdom Queen Mary University of London Wolfson Institute of Population Health London United Kingdom Newcastle University Bioinformatics Support Unit Newcastle upon Tyne United Kingdom Newcastle University Faculty of Medical Sciences Newcastle upon Tyne United Kingdom Queen Mary University of London Centre for Translational Bioinformatics London United Kingdom

ISBN: (纸本)9781665480451

Momentum has been growing into research to better understand the dynamics of multiple long-term conditions - multimorbidity (MLTC-M), defined as the co-occurrence of two or more long-term or chronic conditions within an individual. Several research efforts make use of Electronic Health Records (EHR), which represent patients' medical histories. These range from discovering patterns of multimorbidity, namely by clustering diseases based on their co-occurrence in EHRs, to using EHRs to predict the next disease or other specific outcomes. One problem with the former approach is that it discards important temporal information on the co-occurrence, while the latter requires "big"data volumes that are not always available from routinely collected EHRs, limiting the robustness of the resulting *** this paper we take an intermediate approach, where initially we use about 143,000 EHRs from UK Biobank to perform time-independent clustering using topic modelling, and Latent Dirichlet Allocation specifically. We then propose a metric to measure how strongly a patient is "attracted"into any given cluster at any point through their medical history. By tracking how such gravitational pull changes over time, we may then be able to narrow the scope for potential interventions and preventative measures to specific clusters, without having to resort to full-fledged predictive *** this preliminary work we show exemplars of these dynamic associations, which suggest that further exploration may lead to actionable insights into patients' medical trajectories. © 2022 IEEE.

关键词： Statistics

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POS1431 POTENTIAL DISEASE-MODIFYING EFFECT OF EARLY USE OF METHOTREXATE IN GIANT CELL ARTERITIS

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Annals of the Rheumatic Diseases 2024年 83卷 1091-1092页

作者： J. Berry C. Mun Alice Lin J. Weightman J. Casement B. Thompson J. Heaney K. Baker A. Lorenzi G. Reynolds Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne United Kingdom Musculoskeletal Unit Freeman Hospital Newcastle upon Tyne United Kingdom Bioinformatics Support Unit Newcastle University Newcastle upon Tyne United Kingdom

Background: Glucocorticoids remain the principal treatment for giant cell arteritis (GCA), despite causing significant comorbidity including osteoporosis, infection, and diabetes. The anti-IL6 receptor inhibitor tocilizumab has demonstrated benefit as a steroid-sparing agent, though its use in many countries including the UK is limited to a minority of patients with relapsing or refractory disease. Methotrexate is commonly used in practice but evidence for its effectiveness as a steroid-sparing agent or in maintaining remission is equivocal. In other immune-mediated rheumatic diseases, early treatment with methotrexate can improve long-term outcomes and rates of remission. In this cohort study, we aimed to assess whether early use of methotrexate in GCA influences the long-term prognosis including rates of relapse following completion of glucocorticoid taper. Objectives: The primary outcome was time to first relapse following completion of glucocorticoid taper. Methods: We included all consecutive patients referred to the Fast Track GCA service at the Freeman Hospital in Newcastle and given a diagnosis of GCA between December 2016 to December 2020 (Newcastle and North Tyneside Research Ethics Committee, 16/NE/0319). Methotrexate is not a standard of care in our service, with the decision to initiate treatment influenced by both physician and patient preference and comorbidities. Baseline clinical data is prospectively recorded in a clinical database and longitudinal outcome data is captured through retrospective case notes review. Results: 124 consecutive patients with confirmed GCA were included in analyses, of which 77 (62%) started methotrexate during glucocorticoid taper. Median follow-up was 41.8 months (IQR 32.5 - 56.1) for the entire cohort. There was no significant difference in daily prednisolone dose between those treated with or without methotrexate at 6 months (8mg vs. 9mg, p = 0.56) and 12 months (3mg vs 3mg, p = 0.71) after diagnosis. Completion of glu

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