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- Bonetti, A, et al.
(author)
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RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1018-
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Journal article (peer-reviewed)abstract
- Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA–chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type–specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.
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- Castelo-Branco, A., et al.
(author)
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Treatment patterns in patients with multiple sclerosis : a single hospital cohort study in Sweden
- 2021
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In: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 732-732
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Journal article (other academic/artistic)abstract
- Introduction: An increasing number of disease-modifying therapies (DMT) for multiple sclerosis (MS) has led to switching between treatments.Objectives: In a Swedish MS cohort study, we analysed switching treatment patterns, including prescribed symptomatic medications, before and after an MS diagnosis.Methods: A national incident MS cohort diagnosed in 2008–2016 in the Swedish National Patient Register was linked to the national Prescribed Drug Register. A subcohort in the electronic medical records (EMR) of the Karolinska University Hospital was analysed for medication usage.Results: Patients with an MS diagnosis in the EMR cohort (n=1289) were identified (female, 68.2%; mean age (standard deviation), 38.8 (12.2) years). Prescribed symptomatic medications in the year before cohort entry included analgesics (23.2%), antidepressants (13.9%), opioids (13.4%), systemic corticosteroids (11.2%), and anxiolytics (10.0%). In the 4 years after cohort entry, medications included analgesics (65.2%), systemic antibacterials (55.9%), anti-inflammatory and antirheumatics (50.1%), antidepressants (34.8%), anxiolytics (21.1%), antiepileptics (19.1%) and ophthalmic drugs (16.6%). Of 1289 patients, 1040 were prescribed a DMT (80.7%). Median time (months, interquartile range) to first usage of new DMTs by age group was 1.71, 0.82–4.30 (<40 years); 1.87, 0.95–7.00 (40–59 years); and 3.96, 1.15–12.16 (⩾60 years). The most common DMTs (n=patients) were first-line (n=1054): interferons (55.9%), rituximab (15.7%), dimethyl fumarate (9.1%), natalizumab (7.4%), glatiramer acetate (7.1%), fingolimod (3.5%); second-line (n=551): rituximab (29.4%), natalizumab (19.4%), dimethyl fumarate (17.6%), fingolimod (16.3%), glatiramer acetate (7.8%), interferons (3.1%), teriflunomide (2.2%); third-line (n=184): rituximab (51.1%), natalizumab (13.0%), interferons (9.8%), fingolimod (9.8%), dimethyl fumarate (6.0%).Conclusions: These data indicate high usage of prescribed symp-tomatic medications before and after the MS diagnosis, which may indicate the consequences of prodromal and early sympto-matic MS. Most patients were treated with a DMT within months of diagnosis, with predominant initial use of interferons, and switching to more potent agents in later lines of therapy. Prescribing patterns are changing and expected to evolve further with earlier use of powerful agents.
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- Deng, YX, et al.
(author)
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Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level
- 2022
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 375:6581, s. 681-
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Journal article (peer-reviewed)abstract
- Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling of histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, and next-generation sequencing. Spatially resolved chromatin states in mouse embryos revealed tissue-type-specific epigenetic regulations in concordance with ENCODE references and provide spatial information at tissue scale. Spatial-CUT&Tag revealed epigenetic control of the cortical layer development and spatial patterning of cell types determined by histone modification in mouse brain. Single-cell epigenomes can be derived in situ by identifying 20-micrometer pixels containing only one nucleus using immunofluorescence imaging. Spatial chromatin modification profiling in tissue may offer new opportunities to study epigenetic regulation, cell function, and fate decision in normal physiology and pathogenesis.
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