| 1. |
- Berghoff, Bork A., et al.
(författare)
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RNA-sequence data normalization through in silico prediction of reference genes : the bacterial response to DNA damage as case study
- 2017
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Ingår i: BioData Mining. - : Springer Science and Business Media LLC. - 1756-0381. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Measuring how gene expression changes in the course of an experiment assesses how an organism responds on a molecular level. Sequencing of RNA molecules, and their subsequent quantification, aims to assess global gene expression changes on the RNA level (transcriptome). While advances in high-throughput RNA-sequencing (RNA-seq) technologies allow for inexpensive data generation, accurate post-processing and normalization across samples is required to eliminate any systematic noise introduced by the biochemical and/or technical processes. Existing methods thus either normalize on selected known reference genes that are invariant in expression across the experiment, assume that the majority of genes are invariant, or that the effects of up-and down-regulated genes cancel each other out during the normalization.Results: Here, we present a novel method, moose(2), which predicts invariant genes in silico through a dynamic programming (DP) scheme and applies a quadratic normalization based on this subset. The method allows for specifying a set of known or experimentally validated invariant genes, which guides the DP. We experimentally verified the predictions of this method in the bacterium Escherichia coli, and show how moose(2) is able to (i) estimate the expression value distances between RNA-seq samples, (ii) reduce the variation of expression values across all samples, and (iii) to subsequently reveal new functional groups of genes during the late stages of DNA damage. We further applied the method to three eukaryotic data sets, on which its performance compares favourably to other methods. The software is implemented in C++ and is publicly available from http://grabherr.github.io/moose2/.Conclusions: The proposed RNA-seq normalization method, moose(2), is a valuable alternative to existing methods, with two major advantages: (i) in silico prediction of invariant genes provides a list of potential reference genes for downstream analyses, and (ii) non-linear artefacts in RNA-seq data are handled adequately to minimize variations between replicates.
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| 2. |
- Chen, Jun, et al.
(författare)
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Clinal Variation at Phenology-Related Genes in Spruce : Parallel Evolution in FTL2 and Gigantea?
- 2014
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 197:3, s. 1025-1038
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Tidskriftsartikel (refereegranskat)abstract
- Parallel clines in different species, or in different geographical regions of the same species, are an important source of information on the genetic basis of local adaptation. We recently detected latitudinal clines in SNPs frequencies and gene expression of candidate genes for growth cessation in Scandinavian populations of Norway spruce (Picea abies). Here we test whether the same clines are also present in Siberian spruce (P. obovata), a close relative of Norway spruce with a different Quaternary history. We sequenced nine candidate genes and 27 control loci and genotyped 14 SSR loci in six populations of P. obovata located along the Yenisei river from latitude 56 N to latitude 67 N. In contrast to Scandinavian Norway spruce that both departs from the standard neutral model (SNM) and shows a clear population structure, Siberian spruce populations along the Yenisei do not depart from the SNM and are genetically unstructured. Nonetheless, as in Norway spruce, growth cessation is significantly clinal. Polymorphisms in photoperiodic (FTL2) and circadian clock (Gigantea, GI, PRR3) genes also show significant clinal variation and/or evidence of local selection. In GI, one of the variants is the same as in Norway spruce. Finally, a strong cline in gene expression is observed for FTL2, but not for GI. These results, together with recent physiological studies, confirm the key role played by FTL2 and circadian clock genes in the control of growth cessation in spruce species and suggest the presence of parallel adaptation in these two species.
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| 3. |
- Kallman, Thomas F., et al.
(författare)
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PREVALENCE OF ANALGESIC USE IN PATIENTS WITH CHRONIC PAIN REFERRED TO A MULTIDISCIPLINARY PAIN CENTRE AND ITS CORRELATION WITH PATIENT-REPORTED OUTCOME MEASURES: A CROSS-SECTIONAL, REGISTRY- BASED STUDY
- 2020
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Ingår i: Journal of Rehabilitation Medicine. - : FOUNDATION REHABILITATION INFORMATION. - 1650-1977 .- 1651-2081. ; 52:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic pain is prevalent in Sweden, nearing 20% in the adult population. Treatment often requires a multimodal approach, with medication, physical therapy and psychological interventions. However, the frequency of medication in patients with chronic pain in Sweden, and its correlation with patient-reported outcome measures (PROMs), are currently unknown. Objectives: To investigate the frequency of use of analgesics and other medication in patients with chronic pain referred to a multidisciplinary pain centre, and how opioid treatment relates to PROMs. Design: Cross-sectional, registry-based study. Patients: New referral visits (n = 1,275) to the Pain and Rehabilitation Center in Linkoping, Sweden in 2015. 441 patients had complete medication and PROM data. Methods: Patient-reported analgesic and other medications were matched with patient PROM data from the Swedish Quality Registry for Pain Rehabilitation. Univariate analysis was conducted with IBM Statistical Package for the Social Sciences (SPSS; IBM Corporation, Somers, NY, USA) version 24.0, and multivariate analysis with SIMCA-P+ (version 13, Umetrics AB, Umea, Sweden), with a special emphasis on opioids. Results: n = 132 (30%) patients used opioids daily, and this group differed from other patients on many PROMs, with medium effect sizes for pain severity, interference, health-related quality of life, activity engagement, and satisfaction with social life. Multivariate analysis identified four groups and showed that daily use of opioids was significantly correlated with high pain intensity and low physical functioning. Conclusion: Prevalence of daily opioid use was 30% and daily opioid use did not correlate with better outcome of PROMs. Longitudinal studies are warranted (e.g. on the clinical effect of tapering), as are studies that can better explain the medication variability in patients with complex chronic pain.
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| 4. |
- Kallman, Thomas F., et al.
(författare)
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Salivary beta-endorphin and substance P are not biomarkers of neuropathic chronic pain propensity
- 2018
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe pathophysiology of chronic pain is complex, with most of our knowledge being derived from preclinical studies. The search for biomarkers mirroring the pathophysiology of chronic pain is ongoing, and there is an increasing interest in saliva as a diagnostic tool. Given what is known about salivary substance Pand salivary gland innervation, we hypothesized that salivary substance P and/or beta-endorphin might reflect the basal activity of these neuropeptides in the central nervous system, thereby perhaps mirroring a general propensity to chronic pain. Based on this overall hypothesis, our aim was to compare salivary levels of these neuropeptides in chronic neuropathic pain patients with healthy controls. An additional aim was to relate salivary levels to plasma levels.Materials and methodsWe compared salivary concentrations of beta-endorphin and substance P in 14 chronic neuropathic pain patients with concentrations in 18 healthy controls using a Luminex technology kit. Salivary-to-plasma quotients were also calculated.ResultsWe found no significant difference between the groups' salivary concentrations of substance P and beta-endorphin. No correlation was found between salivary and plasma concentrations of each neuropeptide, which we hypothesize might point to local production of beta-endorphin and/or substance P in the salivary glands. Given high substance P salivary-to-plasma quotients, such a local production seems more likely for substance P than for beta-endorphin.ConclusionsPropensity to neuropathic chronic pain was not substantiated by our analysis of salivary levels of substance P and/or beta-endorphin. However, we report salivary-to-plasma quotients that give potentially important physiological insight about these neuropeptides.
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| 5. |
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| 6. |
- Larsson, Hanna, et al.
(författare)
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Distribution of Long-Range Linkage Disequilibrium and Tajima's D Values in Scandinavian Populations of Norway Spruce (Picea abies)
- 2013
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Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 3:5, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- The site frequency spectrum of mutations (SFS) and linkage disequilibrium (LD) are the two major sources of information in population genetics studies. In this study we focus on the levels of LD and the SFS and on the effect of sample size on summary statistics in 10 Scandinavian populations of Norway spruce. We found that previous estimates of a low level of LD were highly influenced by both sampling strategy and the fact that data from multiple loci were analyzed jointly. Estimates of LD were in fact heterogeneous across loci and increased within individual populations compared with the estimate from the total data. The variation in levels of LD among populations most likely reflects different demographic histories, although we were unable to detect population structure by using standard approaches. As in previous studies, we also found that the SFS-based test Tajima's D was highly sensitive to sample size, revealing that care should be taken to draw strong conclusions from this test when sample size is small. In conclusion, the results from this study are in line with recent studies in other conifers that have revealed a more complex and variable pattern of LD than earlier studies suggested and with studies in trees and humans that suggest that Tajima's D is sensitive to sample size. This has large consequences for the design of future association and population genetic studies in Norway spruce.
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| 7. |
- Lind, Mårten, et al.
(författare)
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A Picea abies Linkage Map Based on SNP Markers Identifies QTLs for Four Aspects of Resistance to Heterobasidion parviporum Infection
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7, s. e101049-
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Tidskriftsartikel (refereegranskat)abstract
- A consensus linkage map of Picea abies, an economically important conifer, was constructed based on the segregation of 686 SNP markers in a F-1 progeny population consisting of 247 individuals. The total length of 1889.2 cM covered 96.5% of the estimated genome length and comprised 12 large linkage groups, corresponding to the number of haploid P. abies chromosomes. The sizes of the groups (from 5.9 to 9.9% of the total map length) correlated well with previous estimates of chromosome sizes (from 5.8 to 10.8% of total genome size). Any locus in the genome has a 97% probability to be within 10 cM from a mapped marker, which makes the map suited for QTL mapping. Infecting the progeny trees with the root rot pathogen Heterobasidion parviporum allowed for mapping of four different resistance traits: lesion length at the inoculation site, fungal spread within the sapwood, exclusion of the pathogen from the host after initial infection, and ability to prevent the infection from establishing at all. These four traits were associated with two, four, four and three QTL regions respectively of which none overlapped between the traits. Each QTL explained between 4.6 and 10.1% of the respective traits phenotypic variation. Although the QTL regions contain many more genes than the ones represented by the SNP markers, at least four markers within the confidence intervals originated from genes with known function in conifer defence; a leucoanthocyanidine reductase, which has previously been shown to upregulate during H. parviporum infection, and three intermediates of the lignification process; a hydroxycinnamoyl CoA shikimate/quinate hydroxycinnamoyltransferase, a 4-coumarate CoA ligase, and a R2R3-MYB transcription factor.
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| 8. |
- Markenroth, Karin, 1973, et al.
(författare)
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Crossing the dripline to N-11 using elastic resonance scattering
- 2000
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 6203:3
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Tidskriftsartikel (refereegranskat)abstract
- The level structure of the unbound nucleus N-11 has been studied by C-10+p elastic resonance scattering in inverse geometry with the LISE3 spectrometer at GANIL, using a C-10 beam with an energy of 9.0 MeV/ nucleon. An additional measurement was done at the A1200 spectrometer at MSU. The excitation function above the C-10+p threshold has been determined up to 5 MeV. A potential-model analysis revealed three resonance states at energies 1.27(-0.05)(+0.18) MeV (Gamma = 1.44 +/- 0.2 MeV), 2.01(-0.05)(+0.15) MeV (Gamma = 0.84 +/- 0.2 MeV), and 3.75 +/- 0.05 MeV (Gamma = 0.60 +/- 0.05 MeV) with the spin-parity assignments I-pi=1/2+,1/2,-,5/2+, respectively. Hence, N-11 is shown to have a ground state parity inversion completely analogous to its mirror partner Be-11. A narrow resonance in the excitation function at 4.33 +/- 0.05 MeV was also observed and assigned spin parity 3/2-.
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| 9. |
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