| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 7. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 8. |
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| 9. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 10. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 11. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 12. |
- Brizuela, F., et al.
(författare)
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High resolution full-field imaging of nanostructures using compact extreme ultraviolet lasers
- 2009
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Ingår i: 9TH INTERNATIONAL CONFERENCE ON X-RAY MICROSCOPY. - : IOP Publishing.
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Konferensbidrag (refereegranskat)abstract
- Recent advances in the development of high peak brightness table-top extreme ultraviolet (EUV) and soft x-ray (SRX) lasers have opened new opportunities for the demonstration of compact full-field EUV/SXR microscopes capable of capturing images with short exposures down to a single laser shot. We demonstrate the practical application of table-top zone plate EUV microscopes that can image nanostructures with a spatial resolution of 54 nm and below and exposure times as short as 1.2 ns, the duration of a single laser shot.
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| 13. |
- Sokolov, Aleksandr V., et al.
(författare)
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Brain Cancer Drug Discovery : Clinical Trials, Drug Classes, Targets, and Combinatorial Therapies
- 2021
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Ingår i: Pharmacological Reviews. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0031-6997 .- 1521-0081. ; 73:4, s. 1-32
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Forskningsöversikt (refereegranskat)abstract
- Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials. gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. Significance Statement-This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.
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| 14. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 15. |
- Brizuela, F., et al.
(författare)
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Near-wavelength Resolution Extreme Ultraviolet Imaging With a Desktop-size Laser
- 2008
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Ingår i: 2008 CONFERENCE ON LASERS AND ELECTRO-OPTICS & QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE, VOLS 1-9. ; , s. 400-401
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Konferensbidrag (refereegranskat)abstract
- We have realized the first demonstration of imaging in the extreme ultraviolet (EUV) with near-wavelength spatial resolution, 54 nm, using a uniquely compact full-field microscope that can produce images with a single one nanosecond exposure.
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| 16. |
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| 17. |
- Brewer, Courtney A., et al.
(författare)
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High spatial resolution full-field microscopy using a desktop-size soft x-ray laser
- 2007
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Ingår i: Proceedings of SPIE. - : SPIE.
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Konferensbidrag (refereegranskat)abstract
- Images with nanoscale resolution were obtained in both transmission and reflection modes using a full-field microscope that is illuminated by an extremely compact λ = 46.9 nm (hv = 26.4 eV) soft x-ray laser. The microscope was used to image the surface of partially processed silicon semiconductor chips containing periodic patterns of polysilicon and metal lines. To characterize the microscope, modulation transfer functions were experimentally built for three different objective zone plates, and images with near-wavelength resolution were obtained.
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| 18. |
- Brewer, Courtney A., et al.
(författare)
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Single-shot extreme ultraviolet laser imaging of nanostructures with wavelength resolution
- 2008
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Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 33:5, s. 518-520
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Tidskriftsartikel (refereegranskat)abstract
- We have demonstrated near-wavelength resolution microscopy in the extreme ultraviolet. Images of 50 nm diameter nanotubes were obtained with a single ~1 ns duration pulse from a desktop-size 46.9 nm laser. We measured the modulation transfer function of the microscope for three different numerical aperture zone plate objectives, demonstrating that 54 nm half-period structures can be resolved. The combination of near-wavelength spatial resolution and high temporal resolution opens myriad opportunities in imaging, such as the ability to directly investigate dynamics of nanoscale structures.
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| 19. |
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| 20. |
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| 21. |
- Menoni, C. S., et al.
(författare)
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Advances in Nanoscale Resolution Soft X-Ray Laser Microscopy
- 2009
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Ingår i: X-RAY LASERS 2008, PROCEEDINGS. - : Springer Netherlands. - 9781402099236 ; , s. 341-347
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Konferensbidrag (refereegranskat)abstract
- We review our most recent results on table-top, nanometer-scale resolution, microscopy using compact soft x-ray lasers developed at Colorado State University. We have realized the first demonstration of wavelength-resolution microscopy in the soft x-ray spectral range. Images of carbon nanotubes, 50 nm in diameter, were obtained with a single similar to 1 ns duration laser pulse from a desk-top size capinary discharge 46.9 nm laser. We fully characterized the new microscope by measuring the modulation transfer function of the instrument for zone plate objectives with three different numerical apertures, demonstrating that 54 nm half-period structures can be resolved. The combination of near-wavelength spatial resolution with high temporal resolution imaging opens myriad opportunities for imaging nanoscale structures.
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| 22. |
- Menoni, C. S., et al.
(författare)
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Nanometer-scale imaging and ablation with Extreme Ultraviolet lasers
- 2007
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Ingår i: 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5. - 9781424435906 ; , s. 1401-1402
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Konferensbidrag (refereegranskat)abstract
- The short wavelength and high brightness of compact extreme ultraviolet lasers is shown to enable the development of microscopes with spatial resolution of tens of nanometers and new types of nanoprobes.
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| 23. |
- Menoni, C. S., et al.
(författare)
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Nanoscale resolution microscopy and ablation with extreme ultraviolet lasers
- 2007
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Ingår i: 2007 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2. - 9781424409242 ; , s. 488-489
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Konferensbidrag (refereegranskat)abstract
- We obtain a spatial resolution down to 38 run with full field imaging and laser-ablation systems that exploit the short wavelength and high brightness output from compact extreme ultraviolet lasers in combination with zone plate optics.
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| 24. |
- Mischak, Harald, et al.
(författare)
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Implementation of proteomic biomarkers : making it work
- 2012
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 42:9, s. 1027-1036
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Tidskriftsartikel (refereegranskat)abstract
- While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare.
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| 25. |
- Allely, Clare Sarah, et al.
(författare)
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Sexual offending and autism spectrum disorders
- 2016
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Ingår i: Journal of Intellectual Disabilities and Offending Behaviour. - 2050-8824. ; 7:1, s. 35-51
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – Studies have found innate vulnerabilities which potentially may increase the risk of an individual with autism spectrum disorders (ASD) finding themselves involved with the criminal justice system as a result of being charged with a sexual offence. The purpose of this paper is to evaluate the literature which has explored sexual offending in individuals with ASD. Design/methodology/approach – A systematic PRISMA review (PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted using internet-based bibliographic databases (PsycINFO, MEDLINE, Psychology and Behavioural Sciences Collection and PsycARTICLES) in order to access studies which investigated to any degree the association between ASD and sexual offending. Findings – Only a small number of case reports (n=7) on sexual offending in individuals with ASD and a small number of prevalence studies (n=7) were identified. Research limitations/implications – Research is urgently required to identify the specific requirements and needs of sexual offenders with ASD in order to inform an appropriate treatment strategy for successful outcomes. Originality/value – Relatively few studies and reviews have investigated the area of ASD and sexual offending specifically. © 2016, © Emerald Group Publishing Limited.
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