| 1. |
- Gurke, Robert, et al.
(författare)
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Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:10
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Forskningsöversikt (refereegranskat)abstract
- The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in similar to 30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients.
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| 2. |
- Hannon, Eilis, et al.
(författare)
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DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.
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| 3. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 4. |
- Moore, Paul A., et al.
(författare)
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Assessing the peatland hummock-hollow classification framework using high-resolution elevation models : implications for appropriate complexity ecosystem modeling
- 2019
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Ingår i: Biogeosciences. - : COPERNICUS GESELLSCHAFT MBH. - 1726-4170 .- 1726-4189. ; 16:18, s. 3491-3506
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Tidskriftsartikel (refereegranskat)abstract
- The hummock-hollow classification framework used to categorize peatland ecosystem microtopography is pervasive throughout peatland experimental designs and current peatland ecosystem modeling approaches. However, identifying what constitutes a representative hummock-hollow pair within a site and characterizing hummock-hollow variability within or between peatlands remains largely unassessed. Using structure from motion (SfM), high-resolution digital elevation models (DEMs) of hummock-hollow microtopography were used to (1) examine how much area needs to be sampled to characterize site-level microtopographic variation; and (2) examine the potential role of microtopographic shape/structure on biogeochemical fluxes using plot-level data from nine northern peatlands. To capture 95% of site-level microtopographic variability, on average, an aggregate sampling area of 32 m(2) composed of 10 randomly located plots was required. Both site(i.e. transect data) and plot-level (i.e. SfM-derived DEM) results show that microtopographic variability can be described as a fractal at the submeter scale, where contributions to total variance are very small below a 0.5 m length scale. Microtopography at the plot level was often found to be non-bimodal, as assessed using a Gaussian mixture model (GMM). Our findings suggest that the non-bimodal distribution of microtopography at the plot level may result in an undersampling of intermediate topographic positions. Extended to the modeling domain, an underrepresentation of intermediate microtopographic positions is shown to lead to potentially large flux biases over a wide range of water table positions for ecosystem processes which are non-linearly related to water and energy availability at the moss surface. Moreover, our simple modeling results suggest that much of the bias can be eliminated by representing microtopography with several classes rather than the traditional two (i.e. hummock/hollow). A range of tools examined herein can be used to easily parameterize peatland models, from GMMs used as simple transfer functions to spatially explicit fractal landscapes based on simple power-law relations between microtopographic variability and scale.
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| 5. |
- Chakera, Annette H., et al.
(författare)
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EANM-EORTC general recommendations for sentinel node diagnostics in melanoma
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:10, s. 1713-1742
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Forskningsöversikt (refereegranskat)abstract
- The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, ( 8) use of dye, ( 9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.
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| 6. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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