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PubMed2026

VisPan: real-time visualisation of multiplex amplicon-based sequencing panels for rapid syndromic surveillance and pathogen detection.

MOTIVATION: Infectious diseases persist as a major global public health challenge. Diverse factors, including climate change, globalization, deforestation, human-animal interactions, lifestyle choices, and various biological factors, can contribute to their emergence and reemergence. Rapid detection and characterization of (re)emerging pathogens are therefore critical for effective outbreak management and for enhancing our understanding of epidemics by monitoring the transmission, spread, evolution, and genomics of pathogens. In this context, next-generation sequencing technologies (NGS), particularly long-read platforms such as Oxford Nanopore Technologies (ONT), have opened new avenues for real-time pathogen monitoring. However, the bioinformatics bottleneck remains a challenge, emphasizing the need for efficient, accessible, and user-friendly analysis tools. RESULTS: Here, we present a tool adapted from the RAMPART software that enables real-time data visualisation of multiplex PCR syndromic panels combined with Oxford Nanopore sequencing. This real-time analysis enables rapid pathogen detection, from raw data acquisition to taxonomic assignment, within minutes. The interface offers dynamic visual tracking of the sequencing run and amplicon coverage, facilitating immediate insights during diagnostic workflows. Validation experiments confirmed the system's reliability, accurately identifying all pathogens present in complex clinical or environmental samples. This tool provides an integrated, user-friendly solution for genomic pathogen surveillance in field or clinical settings.

Software↗

PubMed2024

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

OBJECTIVES: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis. METHODS: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). An optimised approach to standardisation was developed. Technical confounders and batch-effects were identified and adjusted for. Poorly performing SOMAmers and samples were excluded. Variance in the data was determined by principal component (PC) analysis. RESULTS: A synovial fluid standardised protocol was optimised that had good reliability (<20% co-efficient of variation for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. 1720 samples and >6290 SOMAmers met inclusion criteria. 48% of data variance (PC1) was strongly correlated with individual SOMAmer signal intensities, particularly with low abundance proteins (median correlation coefficient 0.70), and was enriched for nuclear and non-secreted proteins. We concluded that this component was predominantly intracellular proteins, and could be adjusted for using an 'intracellular protein score' (IPS). PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. CONCLUSIONS: We have developed a robust method for analysing synovial fluid protein, creating a molecular and clinical dataset of unprecedented scale to explore potential patient subtypes and the molecular pathogenesis of OA. Such methodology underpins the development of new approaches to tackle this disease which remains a huge societal challenge.

Humans↗

PubMed2025

RNAcare: integrating clinical data with transcriptomic evidence using rheumatoid arthritis as a case study.

BACKGROUND: Gene expression analysis is a crucial tool for uncovering the biological mechanisms that underlie differences between patient subgroups, offering insights that can inform clinical decisions. However, despite its potential, gene expression analysis remains challenging for clinicians due to the specialised skills required to access, integrate, and analyse large datasets. Existing tools primarily focus on RNA-Seq data analysis, providing user-friendly interfaces but often falling short in several critical areas: they typically do not integrate clinical data, lack support for patient-specific analyses, and offer limited flexibility in exploring relationships between gene expression and clinical outcomes in disease cohorts. Users, including clinicians with a general knowledge of transcriptomics, however, who may have limited programming experience, are increasingly seeking tools that go beyond traditional analysis. To overcome these issues, computational tools must incorporate advanced techniques, such as machine learning, to better understand how gene expression correlates with patient symptoms of interest. RESULTS: Our RNAcare platform, addresses these limitations by offering an interactive and reproducible solution specifically designed for analysing transcriptomic data from patient samples in a clinical context. This enables researchers to directly integrate gene expression data with clinical features, perform exploratory data analysis, and identify patterns among patients with similar diseases. By enabling users to integrate transcriptomic and clinical data, and customise the target label, the platform facilitates the analysis of the relationships between gene expression and clinical symptoms like pain and fatigue. This allows users to generate hypotheses and illustrative visualisations/reports to support their research. As proof of concept, we use RNAcare to link inflammation-related genes to pain and fatigue in rheumatoid arthritis (RA) and detect signatures in the drug response group, confirming previous findings. CONCLUSION: We present a novel computational platform allowing the interpretation of clinical and transcriptomics data in real-time. The platform can be used for data generated by the user, such as the patient data presented here or using published datasets. The platform is available at https://rna-care.mvls.gla.ac.uk/ , and its source code is https://github.com/sii-scRNA-Seq/RNAcare/ .

Humans↗

PubMed2022

A graph-based approach for the visualisation and analysis of bacterial pangenomes.

BACKGROUND: The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation. RESULTS: Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences. CONCLUSIONS: We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.

Bacteria↗

PubMed2026

Global inequities in hepatitis B and C genomic surveillance revealed through an interactive data integration dashboard.

OBJECTIVES: To assess global disparities in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomic surveillance and to develop an integrated platform that links genomic data with epidemiological burden. STUDY DESIGN: Retrospective observational analysis. METHODS: We reviewed existing viral genomic repositories to identify structural and analytical limitations. Subsequently, we integrated 10 996 HBV and 3533 HCV whole-genome sequences (WGS) from public databases with Global Burden of Disease (GBD) estimates to quantify inequities in genomic surveillance across countries and genotypes. Using these data, we developed the open-access Hepatitis Dashboard, incorporating >14 000 sequences from 141 countries with GBD metrics to evaluate representativeness and sequencing coverage relative to disease burden. RESULTS: Marked inequities in hepatitis genomic surveillance were identified. Despite increasing HBV- and HCV-associated mortality, virus sequence availability remains geographically and genotypically skewed-dominated by China and the United States, with substantial underrepresentation of HBV genotype E and HCV genotypes 5 and 8. Many high-endemic countries in Africa and the Western Pacific remain severely undersampled. We detected circulating antiviral drug-resistance mutations and developed a burden-adjusted sequencing coverage metric, revealing that several high-burden countries, including China, Nigeria and India, are among the least represented in global genomic datasets. Projections to 2030 indicate that neither HBV nor HCV are currently on track to meet WHO elimination targets. CONCLUSIONS: The Hepatitis Dashboard provides an integrated, continuously updated resource that links genomic and epidemiological data to quantify and visualise global surveillance gaps. This analysis highlights a critical disconnect between sequencing efforts and public health needs, which may limit the effectiveness of surveillance-informed strategies to support progress toward WHO 2030 elimination goals. By enabling burden-adjusted prioritisation and longitudinal tracking of genomic coverage, the platform supports evidence-based sampling strategies, equitable resource allocation, and monitoring of global progress toward hepatitis elimination.

Humans↗

PubMed1992

A new technique for fractal analysis applied to human, intracerebrally recorded, ictal electroencephalographic signals.

Application of a new method of fractal analysis to human, intracerebrally recorded, ictal electroencephalographic (EEG) signals is reported. 'Frameshift-Richardson' (FR) analysis involves estimation of fractal dimension (1 < FD < 2) of consecutive, overlapping 10-s epochs of digitised EEG data; it is suggested that this technique offers significant operational advantages over use of algorithms for FD estimation requiring preliminary reconstruction of EEG data in phase space. FR analysis was found to reduce substantially the volume of EEG data, without loss of diagnostically important information concerning onset, propagation and evolution of ictal EEG discharges. Arrhythmic EEG events were correlated with relatively increased FD; rhythmic EEG events with relatively decreased FD. It is proposed that development of this method may lead to: (i) enhanced definition and localisation of initial ictal changes in the EEG presumed due to multi-unit activity; and (ii) synoptic visualisation of long periods of EEG data.

Algorithms↗

PubMed1992

Visualization of multimodal image information in medicine.

Radiological and clinical practice can be enhanced by improved access to multimodal image informations. Analysis, visualization, method characteristic image processing and image synthesis is needed not only for the interpretation of the images but also for performing effective consultations with clinical colleagues and computer supported therapy planning and control strategies. The distributed system RADVIS (radiological visualization) is presented which enables the fast display, three dimensional visualization and the modality oriented analysis of multimodal image informations. Based on a unique image format, modality specific evaluation procedures and two- or three dimensional processing tools of image analysis produce the input data for therapy planning programs. The easy use of this multimedia visualisation tool enables radiologists and clinicians to deal with their image data. The description of methods and procedures of the prototype, as well as typical examples of radiologic practice will demonstrate the efficiency of the presented system.

Humans↗

PubMed1990

Measurement of atactic and paretic gait in neuropathies of rats based on analysis of walking tracks.

In 23 Lewis rats 2 forms of neuropathy both with atactic gait were studied by morphometric analysis of walking tracks. In one group of animals experimental allergic neuritis (EAN) was induced which leads to both sensory and motor dysfunction. Clinical symptoms are atactic gait and hindlimb paresis. In another group pyridoxine (vitamin B6) neuropathy was induced which is a purely sensory neuropathy clinically presenting with gait ataxia, too. Track analysis is a simple method that requires no visualisation process and produces significant and reproducible data. The findings were compared with the clinical scores and electrophysiological data. In EAN, toe spreading was impaired early, and at a later stage stride width, print length and outward rotation of the hind feet changed. Pyridoxine-induced neuropathy produced only an increase in stride width. Track analysis correlated well with clinical grading and electrophysiological recordings. We propose track analysis as a reliable and accurate indicator of neuropathy symptoms in rats.

Animals↗

PubMed1992

Gastrointestinal endoscopy: an accurate and safe primary diagnostic and therapeutic modality.

OBJECTIVE: To review the place of gastrointestinal endoscopy in the management of upper and lower gastrointestinal disorders. DATA SOURCES: We reviewed articles on endoscopy reported over two decades. A Medline search complementing our experience and knowledge of the literature was used to identify the articles. STUDY SELECTION: Papers were selected which focused on indications, comparison with radiology, including clinical outcome measures, and complications. One hundred papers, including those from radiology journals, were reviewed. DATA EXTRACTION: Results of studies are referenced as appropriate. DATA SYNTHESIS AND CONCLUSIONS: Endoscopy allows direct visualisation of the mucosa of the upper gastrointestinal tract, colon and terminal ileum. Subtleties of colour change, vascular pattern abnormalities and scarring are easily detected at endoscopy and are often of diagnostic importance. Endoscopy also provides access for tissue biopsy and allows a wide variety of therapeutic interventions. Traditionally barium studies have been the first step in the evaluation of many gastrointestinal symptoms and still retain cost advantages over endoscopy. However, endoscopy is frequently more sensitive and specific than barium studies. Costs associated with incorrect diagnoses may undermine the apparent cost benefits of barium studies. Advances in endoscopic design have allowed wider therapeutic options and increased safety. Gastrointestinal endoscopy should now be the first line of investigation where diagnostic precision is required or where therapeutic intervention is likely.

Barium Sulfate↗

PubMed1986

Image analysis of the histochemical demonstration of glucose-6-phosphatase activity in rat liver.

Activities of histochemically demonstrated glucose-6-phosphatase were quantified by computerized densitometry using image analysis in livers of female adult Wistar rats fed ad libitum and fasted 22 h before sacrifice. Mean optical densities along the path between small portal tracts and efferent hepatic venous branches and enzyme activities obtained from biochemical assays exhibited a strong positive correlation. The gradients of high periportal to lower perivenous glucose-6-phosphatase activities were analysed by profiles of optical density along these distances. Mapping optical densities in an image of equidensity range provided information on the distribution pattern of hepatic glucose-6-phosphatase over an extended two-dimensional area. This visualisation of histochemical enzyme reaction based on quantitative data supports the approach of sampling across the entire protal----hepatic venous distance disregarding parenchymal zonation. Utilities provided by computer assisted image analysis will have some bearing for further adequate quantitative description of liver function and structural make up.

Animals↗

PubMed1990

Cellular and immunologic features of carotid artery disease in man and experimental animal models.

A better understanding of the pathogenesis of atherosclerosis and of post surgical intimal hyperplasia can be obtained by analysis of the cellular composition of the lesions using immunohistochemical techniques. In the present study, we have compared human atherosclerotic plaques obtained as endarterectomy specimens from the carotid artery, with lesions induced by mechanical injury and cholesterol feeding in rats and rabbits. Antibodies to cell type-specific antigens were used to identify cells, and visualisation was with enzyme-conjugated second antibodies. Our data show that the lipid core region of the human plaque is dominated by macrophages. Such cells also dominate the lesions of cholesterol-fed rabbits. In contrast, intimal lesions induced by balloon catheters in rats consist almost entirely of vascular smooth muscle cells, with a small inflammatory infiltrate of monocytes and T lymphocytes. This situation resembles that in the fibrous cap region of the human plaque. However, the human lesion contains a much higher proportion of T lymphocytes and macrophages than the experimental one. In all types of lesions, class II major histocompatibility antigens were induced on the cells, suggesting that an immune reaction with activation of T lymphocytes may be taking place. Finally, different subpopulations of smooth muscle cells were observed, possibly representing different degrees of differentiation or a response to immune mediators. In conclusion, our studies demonstrate that different experimental models resemble the human disease in various aspects. The choice of experimental model will therefore depend on the problem to be studied. The balloon catheter model should be ideally suited for studies of intimal hyperplasia after surgery and also for studies of fibrous cap formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1977

On the visualisation of nonstationarities in point processes.

A method is described for graphically presenting interval data, such as neural interspike intervals or electrocardiographic R-R intervals, in a form that facilitates the identification of nonstationaries. The method is essentially a plot of isoprobability contours of the cumulative interval histogram, as functions of time. A sequential algorithm is used for updating the contour-line positions. This display is used in an interactive system for visually identifying nonstationarities, and for subsequently comparing selected segments of the data quantitatively using the Kolmogorov-Smirnov test.

Computers↗

PubMed1986

Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices.

The pharmacokinetic basis for using various experimental indices, (urinary drug: metabolite and metabolite:drug + metabolite ratios, urinary metabolite recovery and AUC values), for detecting polymorphic oxidative drug metabolism was examined. Pharmacokinetic determinants in addition to partial metabolic clearance down the polymorphic route were identified in each index. The ability of the various indices to discriminate bimodality in population data was assessed using a computer simulation. With the exception of the AUC data, bimodality was apparent to varying extents in all of the frequency distributions and, in general, logarithmic transformation allowed clearer visualisation of the two phenotypic groups. Simulated distributions were compared with those observed experimentally for metoprolol and its alpha-hydroxy metabolite. Detailed pharmacokinetic data from controlled studies in small numbers of volunteers can form the basis of the input to the simulation programme. Inspection of the output may help in the design of further studies in larger numbers of subjects in whom only limited data collection is possible.

Dealkylation↗

PubMed1987

Senescent vision: is it all the fault of the lens?

Visual decrement correlated with age is often attributed to a progressive deterioration in the optical quality of the ocular media, notably the crystalline lens. Experimental evidence is presented to test the extent to which this hypothesis can be sustained. Recent data on lenticular scatter are shown to be useful in the visualisation and photography of cataract in man.

Adult↗

PubMed1992

Fluorescent CMP-sialic acids as a tool to study the specificity of the CMP-sialic acid carrier and the glycoconjugate sialylation in permeabilized cells.

The specificity of the Golgi carrier for CMP-sialic-acids and the lumenal sialylation of glycoconjugates in mechanically permeabilized cells (semi-intact CHO 15B cells) was studied with CMP-activated fluorescent sialic acids as sensitive markers. Semi-intact cells represent a well-established cellular model for studies on the constitutive secretion pathway because the perforated plasma membrane allows membrane-impermeable CMP-sialic-acids to gain access to cellular organelles. The subcellular structures of semi-intact cells remain morphologically intact and hence synthetic CMP-sialic-acids can be assayed as substrates for the corresponding Golgi sugar-nucleotide transporter. The results prove that the CMP-sialic-acid carrier is able to translocate fluorescent CMP-glycosides, despite the bulky fluoresceinyl residue located at position C5 or C9 of the sialic-acid moiety; the data suggest a slightly higher affinity of the carrier for the C9-substituted CMP-glycoside, whereas the affinity of cellular sialyltransferases is fourfold higher for CMP-5-N-fluoresceinylaminoacetylneuraminic acid (5-FTIUNeuAc; 5-N-fluoresceinylaminoneuraminic acid). Using CMP-9-fluoresceinylthioureido-N-acetylneuraminic acid (CMP-9-FTIUNeuAc), an easy and sensitive fluorometric assay was established for the lumenal sialylation in semi-intact cells. Cellular proteins and gangliosides are both labelled by covalent incorporation of the fluorescent N-acetylneuraminic acid analogue. The assay allows rapid screening for small biomolecules or proteins that influence cellular sialyl transport and sialyl transfer; the lumenal fluorescence incorporation does not require ATP or cytosolic compounds. The suitability of fluorescent CMP-glycosides as markers for intracellular sialylation, proven in this paper, introduces the use of synthetic sialic acids for visualisation of cellular sialic acid pathways by fluorescence microscopy. Based on the data presented here, specific CMP-N-acetylneuraminic-acid analogues can be produced and used for the characterization of the Golgi CMP-sialic-acid carrier.

Animals↗

PubMed1987

Detection of low copy human papilloma virus DNA and mRNA in routine paraffin sections of cervix by non-isotopic in situ hybridisation.

In analysing human papilloma virus (HPV) infection of the cervix in formalin fixed paraffin sections by non-isotopic in situ hybridisation two main problems were found: detachment of sections from the glass during hybridisation and probe detection; inadequate sensitivity and inability to assess sensitivity of the in situ procedure. The first problem was investigated by assessing the efficiency of various tissue adhesives individually and in combination. The second problem was addressed by optimising conditions for DNA unmasking, hybridisation, and biotinylated probe detection. Sensitivity of the final in situ procedure developed was assessed by using the detection of pHY2.1 repeats as a built-in control. Extrapolation of data showed that less than 10 copies of HPV DNA can be visualised by these procedures. HPV nucleic acid, mainly in the form of DNA, was detected not only in koilocytic nuclei but also in suprabasal cells in condylomas and CIN lesions. HPV mRNA was also visualised in the cytoplasm (and probably also nuclei) of the same cell types. These non-isotopic in situ procedures give results comparable to those obtained with radiolabelled probes, but they are less time consuming and provide better morphological resolution.

Cervix Uteri↗

PubMed1986

Development of the Lundia Pro dialyser.

The development of a new plate dialyser with polycarbonate membrane is described. The principles for the dialyser design, the methods for flow visualisation and for determining the residual blood as well as in vitro data for clearance and ultrafiltration are presented. The in vitro results are compared with a corresponding dialyser with a Cuprophan membrane.

Blood↗

PubMed1987

A three-level amplitude discriminator for the separation of multi-unit electrophysiological information.

A device is described that consists of two parallel, three-level differential amplitude discriminators suitable for the selection of electrophysiological data. The present device has been designed for simplicity of construction and operation. The unit allows for a visualisation of the selected levels in precise relationship to the input signal oscilloscope channel. The design eliminates the possibility that a lower level will exceed a higher level. The resulting ease with which complex multi-unit electrophysiological data may be discriminated for analysis using the three digital reference level outputs, makes this instrument suitable for a wide range of electrophysiological experiments.

Electrophysiology↗