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- Almlöf, Jonas Carlsson, et al.
(författare)
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Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e52260-
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.
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| 5. |
- Fang, Li Tai, et al.
(författare)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 6. |
- Guerriero, Giuseppe, et al.
(författare)
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Efficacy of transcutaneous vagus nerve stimulation as treatment for depression: A systematic review
- 2021
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Ingår i: Journal of Affective Disorders Reports. - : Elsevier BV. - 2666-9153. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcutaneous vagus nerve stimulation (tVNS) has been suggested as a treatment method for depression. Methods: A systematic review to systematically evaluate the efficacy of tVNS for the treatment of depression was conducted according to PRISMA guidelines. Primary outcomes were mortality, self-harm, depressive symptoms, and health-related quality of life (HRQoL). Secondary outcomes were anxiety symptoms, medication use, everyday functioning, complications, and patients’ experiences of treatment. Five databases were searched systematically. The included articles were critically appraised and certainty of evidence was assessed using GRADE. Results: Two studies evaluating efficacy and a case series collecting data on complications were included. One randomized trial (n = 37) and one cohort study (n = 160) comparing tVNS with sham-tVNS reported significant reduction in the tVNS group of self-rated (SMD = -0.82, 95%-CI = -1.50, -0.15) but not clinician-rated depressive symptoms, after two weeks, and of both self-rated (SMD = -0.99, 95%-CI = -1.32, -0.66) and clinician-rated (SMD = -0.89, 95%-CI = -1.22, -0.57) depressive symptoms, after four weeks, respectively. Furthermore, the cohort study found reduction of both self-rated (SMD = -0.66, 95%-CI = -0.98, -0.34) and clinician-rated (SMD = -0.14, 95%-CI = -0.46, 0.17) anxiety symptoms. One case series (n = 12), collecting data on complications, reported mild to moderate transient side effects. Limitations: Available studies are few and heterogeneous, have major study limitations, problems with directness and imprecision. Conclusions: It is uncertain whether tVNS reduces depressive symptoms and anxiety. Although existing studies show promising results, further studies are needed to increase the certainty of evidence. © 2021 The Authors
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| 9. |
- Natarajan, E, et al.
(författare)
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Experimental determination of bed agglomeration tendencies of some common agricultural residues in fluidized bed combustion and gasification
- 1998
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Ingår i: Biomass and Bioenergy. - 0961-9534 .- 1873-2909. ; 15:2, s. 163-169
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Tidskriftsartikel (refereegranskat)abstract
- Ever increasing energy demand and the polluting nature of existing fossil fuel energy sources demonstrate the need for other non-polluting and renewable sources of energy. The agricultural residues available in abundance in many countries can be used for power generation. The fluidized bed technology seems to be suitable for converting a wide range of agricultural residues into energy, due to its inherent advantages of fuel flexibility, low operating temperature and isothermal operating condition. The major ash-related problem encountered in fluidized beds is bed agglomeration which, in the worst case, may result in total defluidization and unscheduled downtime. The initial agglomeration temperature for some common tropical agricultural residues were experimentally determined by using a newly developed method based on the controlled fluidized bed agglomeration test. The agricultural residues chosen for the study were rice husk, bagasse, cane trash and olive flesh. The results showed that the initial agglomeration temperatures were less than the initial deformation temperature predicted by the ASTM standard ash fusion tests for all fuels considered. The initial agglomeration temperatures of rice husk and bagasse were more than 1000°C. The agglomeration of cane trash and olive flesh was encountered at relatively low temperatures and their initial agglomeration temperatures in gasification were lower than those in combustion with both bed materials. The use of lime as bed material instead of quartz improved the agglomeration temperature of cane trash and olive flesh in combustion and decreased the same in gasification. The results indicate that rice husk and bagasse can be used in the fluidized bed for energy generation since their agglomeration temperatures are sufficiently high.
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| 10. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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