| 1. |
- Alexandersson, Erik, et al.
(författare)
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Transcriptional regulation of aquaporins in accessions of Arabidopsis in response to drought stress.
- 2010
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Ingår i: Plant Journal. - 1365-313X. ; 61, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Summary Aquaporins facilitate water transport over cellular membranes and are therefore believed to play an important role in water homeostasis. In higher plants aquaporin-like proteins, also called major intrinsic proteins (MIPs), are divided into 5 subfamilies. We have previously shown that MIP transcription in Arabidopsis thaliana generally is down-regulated in leaves upon drought stress, apart from two members of the Plasma membrane Intrinsic Protein (PIP) subfamily, AtPIP1;4 and AtPIP2;5, which are up-regulated. In order to assess if this regulation is general or accession-specific we monitored gene expression of all PIPs in five Arabidopsis accessions. Overall drought regulation of PIPs was well conserved for all five accessions tested suggesting a general and fundamental physiological role of this drought response. In addition, significant differences among accessions were identified for transcripts of three PIP genes. Principal component analysis showed that most of the PIP transcriptional variation during drought stress could be explained by one variable linked to leaf water content. Promoter-GUS constructs of AtPIP1;4, AtPIP2;5 and also AtPIP2;6, which is unresponsive to drought stress, had distinct expression patterns concentrated to the base of the leaf petioles and parts of the flowers. The presence of drought stress response elements within the 1.6 kb promoter regions of AtPIP1;4 and AtPIP2;5, was demonstrated by comparing transcription of the promoter reporter construct and the endogenous gene upon drought stress. Analysis by ATTED-II and other web-based bioinformatical tools showed that several of the MIPs down-regulated upon drought are strongly co-expressed, whereas AtPIP1;4, AtPIP2;5 and AtPIP2;6 are not co-expressed.
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| 2. |
- Duffy, Darragh, et al.
(författare)
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The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis
- 2014
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 59:4, s. 1273-1282
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Tidskriftsartikel (refereegranskat)abstract
- Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. (Hepatology 2014;59:1273-1282)
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| 3. |
- Fontes, Magnus
(författare)
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Optimal results for the nonhomogeneous initial-boundary value problem for the two-dimensional Navier-Stokes equations
- 2010
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Ingår i: Journal of Mathematical Fluid Mechanics. - : Springer Science and Business Media LLC. - 1422-6928 .- 1422-6952. ; 12, s. 412-434
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Tidskriftsartikel (refereegranskat)abstract
- In this work we study the fully nonhomogeneous initial boundary value problem for the two-dimensional time-dependent Navier–Stokes equations in a general open space domain in R2 with low regularity assumptions on the initial and the boundary value data. We show that the perturbed Navier–Stokes operator is a diffeomorphism from a suitable function space onto its own dual and as a corollary we get that the Navier–Stokes equations are uniquely solvable in these spaces and that the solution depends smoothly on all involved data. Our source data space and solution space are in complete natural duality and in this sense, without any smallness assumptions on the data, we solve the equations for data with optimally low regularity in both space and time.
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| 4. |
- Fontes, Magnus, et al.
(författare)
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Simplified a priori Estimate for the Time Periodic Burgers' Equation
- 2010
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Ingår i: Proceedings of the Estonian Academy of Sciences. - : Estonian Academy Publishers. - 1736-6046 .- 1736-7530. ; 59:1, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- We present here a version of the existence and uniqueness result of time periodic solutions to the viscous Burgers’ equation with irregular forcing terms (with Sobolev regularity –1 in space). The key result here is an a priori estimate which is simpler than the previously treated case of forcing terms with regularity –½ in time.
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| 5. |
- Fontes, Magnus, et al.
(författare)
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Statistical and Knowledge Supported Visualization of Multivariate data
- 2012
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Ingår i: Analysis for Science, Engineering and Beyond. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 2190-5622 .- 2190-5614. - 9783642202353 - 9783642202360 ; Springer Proceedings in Mathematics Volume 6, s. 143-173
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Bokkapitel (refereegranskat)abstract
- In the present work we have selected a collection of statistical and mathematical tools useful for the exploration of multivariate data and we present them in a form that is meant to be particularly accessible to a classically trained mathematician. We give self contained and streamlined introductions to principal component analysis, multidimensional scaling and statistical hypothesis testing. Within the presented mathematical framework we then propose a general exploratory methodology for the investigation of real world high dimensional datasets that builds on statistical and knowledge supported visualizations. We exemplify the proposed methodology by applying it to several different genomewide DNA-microarray datasets. The exploratory methodology should be seen as an embryo that can be expanded and developed in many directions. As an example we point out some recent promising advances in the theory for random matrices that, if further developed, potentially could provide practically useful and theoretically well founded estimations of information content in dimension reducing visualizations. We hope that the present work can serve as an introduction to, and help to stimulate more research within, the interesting and rapidly expanding field of data exploration.
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| 6. |
- Fontes, Magnus, et al.
(författare)
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The projection score - an evaluation criterion for variable subset selection in PCA visualization
- 2011
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background In many scientific domains, it is becoming increasingly common to collect high-dimensional data sets, often with an exploratory aim, to generate new and relevant hypotheses. The exploratory perspective often makes statistically guided visualization methods, such as Principal Component Analysis (PCA), the methods of choice. However, the clarity of the obtained visualizations, and thereby the potential to use them to formulate relevant hypotheses, may be confounded by the presence of the many non-informative variables. For microarray data, more easily interpretable visualizations are often obtained by filtering the variable set, for example by removing the variables with the smallest variances or by only including the variables most highly related to a specific response. The resulting visualization may depend heavily on the inclusion criterion, that is, effectively the number of retained variables. To our knowledge, there exists no objective method for determining the optimal inclusion criterion in the context of visualization. Results We present the projection score, which is a straightforward, intuitively appealing measure of the informativeness of a variable subset with respect to PCA visualization. This measure can be universally applied to find suitable inclusion criteria for any type of variable filtering. We apply the presented measure to find optimal variable subsets for different filtering methods in both microarray data sets and synthetic data sets. We note also that the projection score can be applied in general contexts, to compare the informativeness of any variable subsets with respect to visualization by PCA. Conclusions We conclude that the projection score provides an easily interpretable and universally applicable measure of the informativeness of a variable subset with respect to visualization by PCA, that can be used to systematically find the most interpretable PCA visualization in practical exploratory analysis.
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| 7. |
- Lilljebjörn, Henrik, et al.
(författare)
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The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 19:16, s. 3150-3158
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Tidskriftsartikel (refereegranskat)abstract
- The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q) and +16 as possible early events in the leukemogenic process.
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| 8. |
- Soneson, Charlotte, et al.
(författare)
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A framework for list representation, enabling list stabilization through incorporation of gene exchangeabilities.
- 2012
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Ingår i: Biostatistics. - : Oxford University Press (OUP). - 1468-4357 .- 1465-4644. ; 13, s. 129-141
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of multivariate data sets from, for example, microarray studies frequently results in lists of genes which are associated with some response of interest. The biological interpretation is often complicated by the statistical instability of the obtained gene lists, which may partly be due to the functional redundancy among genes, implying that multiple genes can play exchangeable roles in the cell. In this paper, we use the concept of exchangeability of random variables to model this functional redundancy and thereby account for the instability. We present a flexible framework to incorporate the exchangeability into the representation of lists. The proposed framework supports straightforward comparison between any 2 lists. It can also be used to generate new more stable gene rankings incorporating more information from the experimental data. Using 2 microarray data sets, we show that the proposed method provides more robust gene rankings than existing methods with respect to sampling variations, without compromising the biological significance of the rankings.
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| 9. |
- Soneson, Charlotte, et al.
(författare)
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A method for visual identification of small sample subgroups and potential biomarkers
- 2011
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Ingår i: Annals of Applied Statistics. - 1932-6157. ; 5:3, s. 2131-2149
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Tidskriftsartikel (refereegranskat)abstract
- In order to find previously unknown subgroups in biomedical data and generate testable hypotheses, visually guided exploratory analysis can be of tremendous importance. In this paper we propose a new dissimilarity measure that can be used within the Multidimensional Scaling framework to obtain a joint low-dimensional representation of both the samples and variables of a multivariate data set, thereby providing an alternative to conventional biplots. In comparison with biplots, the representations obtained by our approach are particularly useful for exploratory analysis of data sets where there are small groups of variables sharing unusually high or low values for a small group of samples.
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| 10. |
- Soneson, Charlotte, et al.
(författare)
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Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysis.
- 2010
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 40, s. 531-543
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat. Its length can be used to estimate the time of clinical diagnosis, which is defined by overt motor symptoms. Non-motor symptoms begin before motor onset, and involve changes in hypothalamus-regulated functions such as sleep, emotion and metabolism. Therefore we hypothesized that hypothalamic changes occur already prior to the clinical diagnosis. We performed voxel-based morphometry and logistic regression analyses of cross-sectional MR images from 220 HD gene carriers and 75 controls in the Predict-HD study. We show that changes in the hypothalamic region are detectable before clinical diagnosis and that its grey matter contents alone are sufficient to distinguish HD gene carriers from control cases. In conclusion, our study shows, for the first time, that alterations in grey matter contents in the hypothalamic region occur at least a decade before clinical diagnosis in HD using MRI.
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