24 research outputs found
The GLOBE-Consortium: The Next-Generation Genome Viewer
The GLOBE 3D Genome Viewer is the novel system-biology oriented genome browser necessary to access,
present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real
understanding, educative presentation and curative manipulation planning of this tremendous evolutionary
information grail – genomes. This has required completely new approaches to represent the genome architecture
realistically in combination with the various types of informational annotation including experimental data or
instant analysis capabilities. This creates unrivalled new opportunities for scientific researchers, diagnostic users,
educators and publishers as well as PR and commercial applicants. Potential BETA-TESTERS of the GLOBE 3D
Genome Viewer are asked to sign up now
G3DV: A new 3D genome browser and experimental data viewer.
Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of
information. Their system-biological complexity remains, however, still largely mysterious, despite immense
sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional
and regulatory organization. Here, we present the GLOBE 3D Genome Platform a completely novel grid based
virtual “paper” tool and in fact the first system-biological genome browser integrating the holistic complexity of
genomes in a single easy comprehensible platform: Based on a detailed study of biophysical and IT
requirements, every architectural level from sequence to morphology of one or several genomes can be
approached in a real and in a symbolic representation simultaneously and navigated by continuous scale-free
zooming within a unique three-dimensional OpenGL and grid driven environment. In principle an unlimited
number of multi-dimensional data sets can be visualized, customized in terms of arrangement, shape, colour, and
texture etc. as well as accessed and annotated individually or in groups using internal or external data
bases/facilities. Any information can be searched and correlated by importing or calculating simple relations in
real-time using grid resources. A general correlation and application platform for more complex correlative
analysis and a front-end for system-biological simulations both using again the huge capabilities of grid
infrastructures is currently under development. Hence, the GLOBE 3D Genome Platform is an example of a grid
based approach towards a virtual desktop for genomic work combining the three fundamental distributed
resources: i) visual data representation, ii) data access and management, and iii) data analysis and creation. Thus,
the GLOBE 3D Genome Platform is the novel system-biology oriented information system urgently needed to
access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real
understanding, educative presentation and curative manipulation planning of this tremendous evolutionary
information grail – genomes
ImmunoGlobulin galaxy (IGGalaxy) for simple determination and quantitation of immunoglobulin heavy chain rearrangements from NGS
Background: Sequence analysis of immunoglobulin heavy chain (IGH) gene rearrangements and frequency analysis is a powerful tool for studying the immune repertoire, immune responses and immune dysregulation in health and disease. The challenge is to provide user friendly, secure and reproducible analytical services that are available for both small and large laboratories which are determining VDJ repertoire using NGS technology. Results: In this study we describe ImmunoGlobulin Galaxy (IGGalaxy)- a convenient web based application for analyzing next-generation sequencing results and reporting IGH gene rearrangements for both repertoire and clonality studies. IGGalaxy has two analysis options one using the built in igBLAST algorithm and the second using output from IMGT; in either case repertoire summaries for the B-cell populations tested are available. IGGalaxy supports multi-sample and multi-replicate input analysis for both igBLAST and IMGT/HIGHV-QUEST. We demonstrate the technical validity of this platform using a standard dataset, S22, used for benchmarking the performance of antibody alignment utilities with a 99.9 % concordance with previous results. Re-analysis of NGS data from our samples of RAG-deficient patients demonstrated the validity and user friendliness of this tool. Conclusions: IGGalaxy provides clinical researchers with detailed insight into the repertoire of the B-cell population per individual sequenced and between control and pathogenic genomes. IGGalaxy was developed for 454 NGS results but is capable of analyzing alternative NGS data (e.g. Illumina, Ion Torrent). We demonstrate the use of a Galaxy virtual machine to determine the VDJ repertoire for reference data and from B-cells taken from immune deficient patients. IGGalaxy is available as a VM for download and use on a desktop PC or on a server
Prognostically useful gene-expression profiles in acute myeloid leukemia
BACKGROUND: In patients with acute myeloid leukemia (AML) a combination of
methods must be used to classify the disease, make therapeutic decisions,
and determine the prognosis. However, this combined approach provides
correct therapeutic and prognostic information in only 50 percent of
cases. METHODS: We determined the gene-expression profiles in samples of
peripheral blood or bone marrow from 285 patients with AML using
Affymetrix U133A GeneChips containing approximately 13,000 unique genes or
expression-signature tags. Data analyses were carried out with Omniviz,
significance analysis of microarrays, and prediction analysis of
microarrays software. Statistical analyses were performed to determine the
prognostic significance of cases of AML with specific molecular
signatures. RESULTS: Unsupervised cluster analyses identified 16 groups of
patients with AML on the basis of molecular signatures. We identified the
genes that defined these clusters and determined the minimal numbers of
genes needed to identify prognostically important clusters with a high
degree of accuracy. The clustering was driven by the presence of
chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular
genetic mutations (CEBPA), and abnormal oncogene expression (EVI1). We
identified several novel clusters, some consisting of specimens with
normal karyotypes. A unique cluster with a distinctive gene-expression
signature included cases of AML with a poor treatment outcome.
CONCLUSIONS: Gene-expression profiling allows a comprehensive
classification of AML that includes previously identified genetically
defined subgroups and a novel cluster with an adverse prognosis
Characterisation of a major phytoplankton bloom in the River Thames (UK) using flow cytometry and high performance liquid chromatography
Recent river studies have observed rapid phytoplankton dynamics, driven by diurnal cycling and short-term responses to storm events, highlighting the need to adopt new high-frequency characterisation methods to understand these complex ecological systems. This study utilised two such analytical methods; pigment analysis by high performance liquid chromatography (HPLC) and cell counting by flow cytometry (FCM), alongside traditional chlorophyll spectrophotometry and light microscopy screening, to characterise the major phytoplankton bloom of 2015 in the River Thames, UK. All analytical techniques observed a rapid increase in chlorophyll a concentration and cell abundances from March to early June, caused primarily by a diatom bloom. Light microscopy identified a shift from pennate to centric diatoms during this period. The initial diatom bloom coincided with increased HPLC peridinin concentrations, indicating the presence of dinoflagellates which were likely to be consuming the diatom population. The diatom bloom declined rapidly in early June, coinciding with a storm event. There were low chlorophyll a concentrations (by both HPLC and spectrophotometric methods) throughout July and August, implying low biomass and phytoplankton activity.However, FCM revealed high abundances
of pico-chlorophytes and cyanobacteria through July and August, showing that phytoplankton communities remain active and abundant throughout the summer period. In combination, these techniques are able to simultaneously characterise a wider range of phytoplankton groups, with greater certainty, and provide improved understanding of phytoplankton functioning (e.g. production of UV inhibiting pigments by cyanobacteria in response to high light levels) and ecological status (through examination of pigment degradation products). Combined HPLC and FCM analyses offer rapid and cost-effective characterisation of phytoplankton communities at appropriate timescales. This will allow a more-targeted use of light microscopy to capture phytoplankton peaks or to investigate periods of rapid community succession. This will lead to greater system understanding of phytoplankton succession in response to biogeochemical drivers
Recent Advances in i-Gene Tools and Analysis: Microarrays, Next Generation Sequencing and Mass Spectrometry
215-225Recent advances in technology and associated methodology have made
the current period one of the most exciting in molecular biology and medicine.
Underlying these is an appreciation that modern research is driven by
increasing large amounts of data being interpreted by interdisciplinary
collaborative teams which are often geographically dispersed. The availability
of cheap computing power, high speed informatics networks and high quality
analysis software has been essential to this as has the application of modern
quality assurance methodologies. In this review, we discuss the application of
modern ‘High-Throughput’ molecular biological technologies such as
‘Microarrays’ and ‘Next Generation Sequencing’ to scientific and biomedical
research as we have observed. Furthermore in
this review, we also offer some guidance that enables the reader as to
understand certain features of these as well as new strategies and help them to
apply these i-Gene tools in their endeavours successfully. Collectively, we
term this ‘i-Gene Analysis’. We also offer predictions as to the developments
that are anticipated in the near and more distant future.
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The GLOBE 3D Genome Browser
The combination of genome sequence and structure, its annotation and experimental data in an accessible and
comprehensible way is a major challenge. Increasingly, there are a large number of extremely divergent data
sets: the sequence itself, genes, regulatory regions, various forms of reoccurring sequence features and clone sets
etc. Currently, one possibility to represent this information in a visual form - and thus to reveal its scientific
meaning - is to use genome browsers such as "Ensembl" or "The UCSC Genome Browser". These browsers have
been beneficial in the understanding of the complex organization of genomes. However, there are also huge
limitations concerning their focus on linear presentation, standardized input and data bank accessibility. Also
customisability by a remote user with special requirements is difficult.
Therefore, the GLOBE-Consortium has developed the next generation genome viewer - the GLOBE 3D-Viewer
- to visualize multi-dimensional data sets from various sources in an easy intuitive manor while accounting for
the complexity of genome organization. Together with an easily accessible data-warehouse for archiving (un-
)published experimental data and the Erasmus Computing Grid (ECG) for fast interactive large-scale
(correlative) analysis the GLOBE-Consortium creates an intuitive holistic environment for genome research.
Thus, the GLOBE 3D-Viewer sets the new standard to integrate complex genomic data sets within a single
holistic display system and thus is major advance for scientific and clinical genome research
Is there a role for doravirine in African HIV treatment programmes? A large observational resistance study in South Africa
Introduction: Dolutegravir has replaced efavirenz in most low- and middle-income countries, due to better tolerability and formidable resistance profile, but dolutegravir side effects suggest alternatives are needed. We evaluated doravirine resistance in South Africa as a first step to assess whether doravirine may replace dolutegravir. Methods: A retrospective dataset was analysed for predicted doravirine susceptibility, including sequences obtained from three patient groups. First, data from 277 patients initiating antiretroviral treatment (ART) were collected between February 2013 and October 2014 as part of a national survey. Second, data from 788 patients experiencing NNRTI-based ART failure were obtained between February 2013 and October 2014 as part of a national survey. Third, data derived from 584 patients who had genotypic drug resistance testing requested after NNRT-based failure as part of individual patient management between January 2016 and December 2019. Pol sequences were generated using validated population-based in-house genotyping and submitted to Stanford HIVdb v8.9. Results and discussion: Less than 5% of patients initiating ART presented with genotypic doravirine resistance, whereas most patients experiencing NNRTI-based ART failure presented with predicted intermediate (41.0%) or high-level resistance (43.8%) to doravirine. High-level resistance to doravirine was commonly predicted by the presence of at least three DRMs (79.7%). The predicted resistance profile to doravirine in ART-naïve patients is promising, but less so in those experiencing failure to first-generation NNRTIs. Accumulation of NNRTI DRMs seems to be an important factor in the poor resistance prediction for doravirine. Conclusions: Although doravirine is approved as initial therapy in patients who are ART-naïve, it is currently recommended to obtain a genotype prior to the initiation of ART. Clinical studies are needed to ascertain whether predicted resistance profiles in ART naïve and NNRTI-treated patients translate into poor clinical outcomes, especially in settings where genotypic resistance testing is not available