| 1. |
- Asking, Lars, et al.
(författare)
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An electrostatic aerosol sampler
- 1988
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 19:7, s. 1023-1026
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 5. |
- MARTINSSON, BENGT G., et al.
(författare)
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A relative humidity processing method for the sampling of aerosol particles with low growth‐ability
- 1992
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 44:5, s. 632-644
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Tidskriftsartikel (refereegranskat)abstract
- A method for the fractionation of aerosol particles with respect to size and ability to grow with an increased relative humidity has been developed. The system consists of cascade impactors, diffusion driers, a humidifier and a temperature stabiliser. Diffusion driers were designed and the vapour penetration was modelled below 20%. A humidifier which can be operated with an output relative humidity above 95% was developed. Flow‐rates up to 51/min can be used and the relative humidity can be controlled within approximately 1%. The ability of the system to fractionate aerosol particles with respect to growth with relative humidity was investigated. The equivalent aerodynamic diameter growth factor for sodium chloride was determined to 2 at a relative humidity of 98%, in good agreement with theory. The growth is used to collect particles with no, or limited growth with increased relative humidity in separate fractions for chemical characterisation. This is obtained with an impactor stage operated at high relative humidity followed by a diffusion drier and an impactor stage with a factor of 1.4 lower cut‐off diameter operated at low relative humidity, where the particles with low growth‐ability are collected. The system was in operation during the EUROTRAC sub‐project Ground‐based Cloud Experiment (GCE) at Po Valley, supplying important information on the particle size related scavenging and the elemental composition of particles with a low growth‐ability.
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| 6. |
- Staaf, Johan, et al.
(författare)
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RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer
- 2022
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Ingår i: npj Breast Cancer. - : Nature Publishing Group. - 2374-4677. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Multigene assays for molecular subtypes and biomarkers can aid management of early invasive breast cancer. Using RNA-sequencing we aimed to develop single-sample predictor (SSP) models for clinical markers, subtypes, and risk of recurrence (ROR). A cohort of 7743 patients was divided into training and test set. We trained SSPs for subtypes and ROR assigned by nearest-centroid (NC) methods and SSPs for biomarkers from histopathology. Classifications were compared with Prosigna in two external cohorts (ABiM, n = 100 and OSLO2-EMIT0, n = 103). Prognostic value was assessed using distant recurrence-free interval. Agreement between SSP and NC for PAM50 {five subtypes) was high (85%, Kappa = 0.78) for Subtype (four subtypes) very high {90%, Kappa = 0.84) and for ROR risk category high (84%, Kappa = 0.75, weighted Kappa = 0.90). Prognostic value was assessed as equivalent and clinically relevant. Agreement with histopathology was very high or high for receptor status, while moderate for Ki67 status and poor for Nottingham histological grade. SSP and Prosigna concordance was high for subtype (OSLO-EMIT0 83%, Kappa = 0.73 and ABiM 80%, Kappa = 0.72) and moderate and high for ROR risk category (68 and 84%, Kappa = 0.50 and 0.70, weighted Kappa = 0.70 and 0.78). Pooled concordance for emulated treatment recommendation dichotomized for chemotherapy was high (85%, Kappa = 0.66). Retrospective evaluation suggested that SSP application could change chemotherapy recommendations for up to 17% of postmenopausal ER+/HER2-/N0 patients with balanced escalation and de-escalation. Results suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level and that SSP models can be derived to closely match clinical tests.
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