| 1. |
- Andersson, Erik, et al.
(författare)
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Ambio fit for the 2020s
- 2022
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Ingår i: Ambio. - : Springer Nature. - 0044-7447 .- 1654-7209. ; 51:5, s. 1091-1093
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Wadensten, Elisabeth, et al.
(författare)
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Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer.
- 2023
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Ingår i: JCO Precision Oncology (JCO PO). - : American Society of Clinical Oncology. - 2473-4284. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have indicated that broad genomic characterization of childhood cancer provides diagnostically and/or therapeutically relevant information in selected high-risk cases. However, the extent to which such characterization offers clinically actionable data in a prospective broadly inclusive setting remains largely unexplored.We implemented prospective whole-genome sequencing (WGS) of tumor and germline, complemented by whole-transcriptome sequencing (RNA-Seq) for all children diagnosed with a primary or relapsed solid malignancy in Sweden. Multidisciplinary molecular tumor boards were set up to integrate genomic data in the clinical decision process along with a medicolegal framework enabling secondary use of sequencing data for research purposes.During the study's first 14 months, 118 solid tumors from 117 patients were subjected to WGS, with complementary RNA-Seq for fusion gene detection in 52 tumors. There was no significant geographic bias in patient enrollment, and the included tumor types reflected the annual national incidence of pediatric solid tumor types. Of the 112 tumors with somatic mutations, 106 (95%) exhibited alterations with a clear clinical correlation. In 46 of 118 tumors (39%), sequencing only corroborated histopathological diagnoses, while in 59 cases (50%), it contributed to additional subclassification or detection of prognostic markers. Potential treatment targets were found in 31 patients (26%), most commonly ALK mutations/fusions (n = 4), RAS/RAF/MEK/ERK pathway mutations (n = 14), FGFR1 mutations/fusions (n = 5), IDH1 mutations (n = 2), and NTRK2 gene fusions (n = 2). In one patient, the tumor diagnosis was revised based on sequencing. Clinically relevant germline variants were detected in 8 of 94 patients (8.5%).Up-front, large-scale genomic characterization of pediatric solid malignancies provides diagnostically valuable data in the majority of patients also in a largely unselected cohort.
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| 5. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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| 6. |
- Lundström, Erik, Docent, 1964-, et al.
(författare)
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Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden
- 2020
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Ingår i: Trials. - Uppsala : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Studies have suggested that fluoxetine might improve neurological recovery after stroke, but the results remain inconclusive. The EFFECTS (Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke) reached its recruitment target of 1500 patients in June 2019. The purpose of this article is to present all amendments to the protocol and describe how we formed the EFFECTS trial collaboration in Sweden. Methods In this investigator-led, multicentre, parallel-group, randomised, placebo-controlled trial, we enrolled non-depressed stroke patients aged 18 years or older between 2 and 15 days after stroke onset. The patients had a clinical diagnosis of stroke (ischaemic or intracerebral haemorrhage) with persisting focal neurological deficits. Patients were randomised to fluoxetine 20 mg or matching placebo capsules once daily for 6 months. Results Seven amendments were made and included clarification of drug interaction between fluoxetine and metoprolol and the use of metoprolol for severe heart failure as an exclusion criterion, inclusion of data from central Swedish registries and the Swedish Stroke Register, changes in informed consent from patients, and clarification of design of some sub-studies. EFFECTS recruited 1500 patients at 35 centres in Sweden between 20 October 2014 and 28 June 2019. We plan to unblind the data in January 2020 and report the primary outcome in May 2020. Conclusion EFFECTS will provide data on the safety and efficacy of 6 months of treatment with fluoxetine after stroke in a Swedish health system setting. The data from EFFECTS will also contribute to an individual patient data meta-analysis.
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| 7. |
- Giacomello, Stefania, et al.
(författare)
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Spatially resolved transcriptome profiling in model plant species
- 2017
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Ingår i: Nature Plants. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Understanding complex biological systems requires functional characterization of specialized tissue domains. However, existing strategies for generating and analysing high-throughput spatial expression profiles were developed for a limited range of organisms, primarily mammals. Here we present the first available approach to generate and study highresolution, spatially resolved functional profiles in a broad range of model plant systems. Our process includes highthroughput spatial transcriptome profiling followed by spatial gene and pathway analyses. We first demonstrate the feasibility of the technique by generating spatial transcriptome profiles from model angiosperms and gymnosperms microsections. In Arabidopsis thaliana we use the spatial data to identify differences in expression levels of 141 genes and 189 pathways in eight inflorescence tissue domains. Our combined approach of spatial transcriptomics and functional profiling offers a powerful new strategy that can be applied to a broad range of plant species, and is an approach that will be pivotal to answering fundamental questions in developmental and evolutionary biology.
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| 8. |
- Jonsson, Hans, et al.
(författare)
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Genome sequence of segmented filamentous bacteria present in the human intestine
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Segmented filamentous bacteria (SFB) are unique immune modulatory bacteria colonizing the small intestine of a variety of animals in a host-specific manner. SFB exhibit filamentous growth and attach to the host's intestinal epithelium, offering a physical route of interaction. SFB affect functions of the host immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome has been reported. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65-71% average amino acid identity to the others. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB genome. We thus conclude that a unique SFB variant exists in humans and foresee a renewed interest in the elucidation of SFB functionality in this environment.
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| 10. |
- Nystedt, Björn, et al.
(författare)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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