Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) study
Name:
Article-PLoS_Genet-Multi-orga- ...
Size:
1.067Mb
Format:
PDF
Description:
Article - Full Text
Name:
Supplement_1_-_PLoS_Genet-Mult ...
Size:
1.152Mb
Format:
Postscript
Description:
Supplemental File 1
Name:
Supplement_2_-_PLoS_Genet-Mult ...
Size:
3.020Mb
Format:
Postscript
Description:
Supplemental File 2
Type
ArticleAuthors
Hägg, SaraSkogsberg, Josefin
Lundström, Jesper
Noori, Peri
Nilsson, Roland
Zhong, Hua
Maleki, Shohreh
Shang, Ming-Mei
Brinne, Björn
Bradshaw, Maria
Bajic, Vladimir B.
Samnegård, Ann
Silveira, Angela
Kaplan, Lee M.
Gigante, Bruna
Leander, Karin
de Faire, Ulf
Rosfors, Stefan
Lockowandt, Ulf
Liska, Jan
Konrad, Peter
Takolander, Rabbe
Franco-Cereceda, Anders
Schadt, Eric E.
Ivert, Torbjörn
Hamsten, Anders
Tegnér, Jesper
Björkegren, Johan
KAUST Department
Computational Bioscience Research Center (CBRC)Date
2009-12-04Metadata
Show full item recordAbstract
Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n =66/tissue) and atherosclerotic and unaffected arterial wall (n =40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n =15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n= 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n =49/48) and one visceral fat (n =59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P=0.008 and P=0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n =55/54) relating to carotid stenosis (P =0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n= 16/17, P<10 -27and-30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the Amodule was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research. 2009 Hgg et al.Citation
Hägg S, Skogsberg J, Lundström J, Noori P, Nilsson R, et al. (2009) Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study. PLoS Genet 5: e1000754. doi:10.1371/journal.pgen.1000754.Publisher
Public Library of Science (PLoS)Journal
PLoS GeneticsISSN
15537390PubMed ID
19997623PubMed Central ID
PMC2780352Handle URI
http://hdl.handle.net/10754/325276Scopus Count
Related items
Showing items related by title, author, creator and subject.
-
Analysis, reconstruction and manipulation using arterial snakes(Association for Computing Machinery (ACM), 2010)Man-made objects often consist of detailed and interleaving structures, which are created using cane, coils, metal wires, rods, etc. The delicate structures, although manufactured using simple procedures, are challenging to scan and reconstruct. We observe that such structures are inherently 1D, and hence are naturally represented using an arrangement of generating curves. We refer to the resultant surfaces as arterial surfaces. In this paper we approach for analyzing, reconstructing, and manipulating such arterial surfaces. The core of the algorithm is a novel deformable model, called arterial snake, that simultaneously captures the topology and geometry of the arterial objects. The recovered snakes produce a natural decomposition of the raw scans, with the decomposed parts often capturing meaningful object sections. We demonstrate the robustness of our algorithm on a variety of arterial objects corrupted with noise, outliers, and with large parts missing. We present a range of applications including reconstruction, topology repairing, and manipulation of arterial surfaces by directly controlling the underlying curve network and the associated sectional profiles, which are otherwise challenging to perform. © 2010 ACM.
-
A stochastic model for early placental development.(The Royal Society, 2014-08-01)In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.
-
Reconstruction of the residual stresses in a hyperelastic body using ultrasound techniques(Elsevier BV, 2013-09)This paper focuses on a novel approach for characterizing the residual stress field in soft tissue using ultrasound interrogation. A nonlinear inverse spectral technique is developed that makes fundamental use of the finite strain nonlinear response of the material to a quasi-static loading. The soft tissue is modeled as a nonlinear, prestressed and residually stressed, isotropic, slightly compressible elastic body with a rectangular geometry. A boundary value problem is formulated for the residually stressed and prestressed soft tissue, the boundary of which is subjected to a quasi-static pressure, and then an idealized model for the ultrasound interrogation is constructed by superimposing small amplitude time harmonic infinitesimal vibrations on static finite deformation via an asymptotic construction. The model is studied, through a semi-inverse approach, for a specific class of deformations that leads to a system of second order differential equations with homogeneous boundary conditions of Sturm-Liouville type. By making use of the classical theory of inverse Sturm-Liouville problems, and root finding and optimization techniques, several inverse spectral algorithms are developed to approximate the residual stress distribution in the body, given the first few eigenfrequencies of several induced static pressures. © 2013 Elsevier Ltd. All rights reserved.
