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See detailBone marrow-derived mesenchymal stem cells drive lymphangiogenesis.
Maertens, Ludovic ULg; Erpicum, Charlotte ULg; Detry, Benoît ULg et al

in PLoS ONE (2014), 9(9), 106976

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during ... [more ▼]

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. [less ▲]

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See detailA New Look at Ichthyosaur Long Bone Microanatomy and Histology: Implications for Their Adaptation to an Aquatic Life
Houssaye, Alexandra; Scheyer, Torsten; Kolb, Christian et al

in PLoS ONE (2014), 9(4), 95637

Background Ichthyosaurs are Mesozoic reptiles considered as active swimmers highly adapted to a fully open-marine life. They display a wide range of morphologies illustrating diverse ecological grades ... [more ▼]

Background Ichthyosaurs are Mesozoic reptiles considered as active swimmers highly adapted to a fully open-marine life. They display a wide range of morphologies illustrating diverse ecological grades. Data concerning their bone microanatomical and histological features are rather limited and suggest that ichthyosaurs display a spongious, “osteoporotic-like” bone inner structure, like extant cetaceans. However, some taxa exhibit peculiar features, suggesting that the analysis of the microanatomical and histological characteristics of various ichthyosaur long bones should match the anatomical diversity and provide information about their diverse locomotor abilities and physiology. Methodology/Principal Findings The material analyzed for this study essentially consists of mid-diaphyseal transverse sections from stylopod bones of various ichthyosaurs and of a few microtomographic (both conventional and synchrotron) data. The present contribution discusses the histological and microanatomical variation observed within ichthyosaurs and the peculiarities of some taxa (Mixosaurus, Pessopteryx). Four microanatomical types are described. If Mixosaurus sections differ from those of the other taxa analyzed, the other microanatomical types, characterized by the relative proportion of compact and loose spongiosa of periosteal and endochondral origin respectively, seem to rather especially illustrate variation along the diaphysis in taxa with similar microanatomical features. Our analysis also reveals that primary bone in all the ichthyosaur taxa sampled (to the possible exception of Mixosaurus) is spongy in origin, that cyclical growth is a common pattern among ichthyosaurs, and confirms the previous assumptions of high growth rates in ichthyosaurs. Conclusions/Significance The occurrence of two types of remodelling patterns along the diaphysis, characterized by bone mass decrease and increase respectively is described for the first time. It raises questions about the definition of the osseous microanatomical specializations bone mass increase and osteoporosis, notably based on the processes involved, and reveals the difficulty in determining the true occurrence of these osseous specializations in ichthyosaurs. [less ▲]

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See detailEffects of adenosine on lymphangiogenesis.
Lenoir, Bénédicte ULg; Wagner, Daniel R.; Blacher, Silvia ULg et al

in PloS one (2014), 9(3), 92715

BACKGROUND: The lymphatic system controls tissue homeostasis by draining protein-rich lymph to the vascular system. Lymphangiogenesis, the formation of lymphatic vessels, is a normal event in childhood ... [more ▼]

BACKGROUND: The lymphatic system controls tissue homeostasis by draining protein-rich lymph to the vascular system. Lymphangiogenesis, the formation of lymphatic vessels, is a normal event in childhood but promotes tumor spread and metastasis during adulthood. Blocking lymphangiogenesis may therefore be of therapeutic interest. Production of adenosine is enhanced in the tumor environment and contributes to tumor progression through stimulation of angiogenesis. In this study, we determined whether adenosine affects lymphangiogenesis. METHODS: Lymphatic endothelial cells (HMVEC-dLy) were cultured in presence of adenosine and their proliferation, migration and tube formation was assessed. Gelatin sponges embedded with the stable analogue of adenosine 2-chloro adenosine were implanted in mice ear and lymphangiogenesis was quantified. Mice were intravenously injected with adenoviruses containing expression vector for 5'-endonucleotidase, which plays a major role in the formation of adenosine. RESULTS: In vitro, we observed that adenosine decreased the proliferation of lymphatic endothelial cells, their migration and tube formation. However, in vivo, gelatin sponges containing 2-chloro adenosine and implanted in mice ear displayed an elevated level of lymphangiogenesis (2.5-fold, p<0.001). Adenovirus-mediated over-expression of cytosolic 5'-nucleotidase IA stimulated lymphangiogenesis and the recruitment of macrophages in mouse liver. Proliferation of lymphatic endothelial cells was enhanced (2-fold, p<0.001) when incubated in the presence of conditioned medium from murine macrophages. CONCLUSION: We have shown that adenosine stimulates lymphangiogenesis in vivo, presumably through a macrophage-mediated mechanism. This observation suggests that blockade of adenosine receptors may help in anti-cancer therapies. [less ▲]

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See detailWhat is the Ability Emotional Intelligence Test (MSCEIT) good for? An evaluation using item response theory.
Fiori, Marina; Antonietti, Jean-Philippe; Mikolajczak, Moira et al

in PloS one (2014), 9(6), 98827

The ability approach has been indicated as promising for advancing research in emotional intelligence (EI). However, there is scarcity of tests measuring EI as a form of intelligence. The Mayer Salovey ... [more ▼]

The ability approach has been indicated as promising for advancing research in emotional intelligence (EI). However, there is scarcity of tests measuring EI as a form of intelligence. The Mayer Salovey Caruso Emotional Intelligence Test, or MSCEIT, is among the few available and the most widespread measure of EI as an ability. This implies that conclusions about the value of EI as a meaningful construct and about its utility in predicting various outcomes mainly rely on the properties of this test. We tested whether individuals who have the highest probability of choosing the most correct response on any item of the test are also those who have the strongest EI ability. Results showed that this is not the case for most items: The answer indicated by experts as the most correct in several cases was not associated with the highest ability; furthermore, items appeared too easy to challenge individuals high in EI. Overall results suggest that the MSCEIT is best suited to discriminate persons at the low end of the trait. Results are discussed in light of applied and theoretical considerations. [less ▲]

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See detailEffects of visual cortex activation on the nociceptive blink reflex in healthy subjects.
Sava, Simona L.; de Pasqua, Victor; MAGIS, Delphine ULg et al

in PloS one (2014), 9(6), 100198

Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not ... [more ▼]

Bright light can cause excessive visual discomfort, referred to as photophobia. The precise mechanisms linking luminance to the trigeminal nociceptive system supposed to mediate this discomfort are not known. To address this issue in healthy human subjects we modulated differentially visual cortex activity by repetitive transcranial magnetic stimulation (rTMS) or flash light stimulation, and studied the effect on supraorbital pain thresholds and the nociceptive-specific blink reflex (nBR). Low frequency rTMS that inhibits the underlying cortex, significantly decreased pain thresholds, increased the 1st nBR block ipsi- and contralaterally and potentiated habituation contralaterally. After high frequency or sham rTMS over the visual cortex, and rMS over the right greater occipital nerve we found no significant change. By contrast, excitatory flash light stimulation increased pain thresholds, decreased the 1st nBR block of ipsi- and contralaterally and increased habituation contralaterally. Our data demonstrate in healthy subjects a functional relation between the visual cortex and the trigeminal nociceptive system, as assessed by the nociceptive blink reflex. The results argue in favour of a top-down inhibitory pathway from the visual areas to trigemino-cervical nociceptors. We postulate that in normal conditions this visuo-trigeminal inhibitory pathway may avoid disturbance of vision by too frequent blinking and that hypoactivity of the visual cortex for pathological reasons may promote headache and photophobia. [less ▲]

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See detailThe Dimethylsulfide Cycle in the Eutrophied Southern North Sea: A Model Study Integrating Phytoplankton and Bacterial Processes
Gypens, N; Borges, Alberto ULg; Speeckaert, Gaëlle ULg et al

in Plos One (2014), 9(1)(e85862 DOI: 10.1371/journal.pone.0085862),

We developed a module describing the dimethylsulfoniopropionate (DMSP) and dimethylsulfide (DMS) dynamics, including biological transformations by phytoplankton and bacteria, and physico-chemical ... [more ▼]

We developed a module describing the dimethylsulfoniopropionate (DMSP) and dimethylsulfide (DMS) dynamics, including biological transformations by phytoplankton and bacteria, and physico-chemical processes (including DMS air-sea exchange). This module was integrated in the MIRO ecological model and applied in a 0D frame in the Southern North Sea (SNS). The DMS(P) module is built on parameterizations derived from available knowledge on DMS(P) sources, transformations and sinks, and provides an explicit representation of bacterial activity in contrast to most of existing models that only include phytoplankton process (and abiotic transformations). The model is tested in a highly productive coastal ecosystem (the Belgian coastal zone, BCZ) dominated by diatoms and the Haptophyceae Phaeocystis, respectively low and high DMSP producers. On an annual basis, the particulate DMSP (DMSPp) production simulated in 1989 is mainly related to Phaeocystis colonies (78%) rather than diatoms (13%) and nanoflagellates (9%). Accordingly, sensitivity analysis shows that the model responds more to changes in the sulfur:carbon (S:C) quota and lyase yield of Phaeocystis. DMS originates equally from phytoplankton and bacterial DMSP-lyase activity and only 3% of the DMS is emitted to the atmosphere. Model analysis demonstrates the sensitivity of DMS emission towards the atmosphere to the description and parameterization of biological processes emphasizing the need of adequately representing in models both phytoplankton and bacterial processes affecting DMS(P) dynamics. This is particularly important in eutrophied coastal environments such as the SNS dominated by high non-diatom blooms and where empirical models developed from data-sets biased towards open ocean conditions do not satisfactorily predict the timing and amplitude of the DMS seasonal cycle. In order to predict future feedbacks of DMS emissions on climate, it is needed to account for hotspots of DMS emissions from coastal environments that, if eutrophied, are dominated not only by diatoms. [less ▲]

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See detailThe genetic legacy of multiple beaver reintroductions in central Europe
Frosch, C.; Kraus, R. H. S.; Angst, C. et al

in PLoS ONE (2014), 9(5),

The comeback of the Eurasian beaver (Castor fiber) throughout western and central Europe is considered a major conservation success. Traditionally, several subspecies are recognised by morphology and ... [more ▼]

The comeback of the Eurasian beaver (Castor fiber) throughout western and central Europe is considered a major conservation success. Traditionally, several subspecies are recognised by morphology and mitochondrial haplotype, each linked to a relict population. During various reintroduction programs in the 20th century, beavers from multiple source localities were released and now form viable populations. These programs differed in their reintroduction strategies, i.e., using pure subspecies vs. mixed source populations. This inhomogeneity in management actions generated ongoing debates regarding the origin of present beaver populations and appropriate management plans for the future. By sequencing of the mitochondrial control region and microsatellite genotyping of 235 beaver individuals from five selected regions in Germany, Switzerland, Luxembourg, and Belgium we show that beavers from at least four source origins currently form admixed, genetically diverse populations that spread across the study region. While regional occurrences of invasive North American beavers (n = 20) were found, all but one C. fiber bore the mitochondrial haplotype of the autochthonous western Evolutionary Significant Unit (ESU). Considering this, as well as the viability of admixed populations and the fact that the fusion of different lineages is already progressing in all studied regions, we argue that admixture between different beaver source populations should be generally accepted. © 2014 Frosch et al. [less ▲]

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See detailFirst Clarkforkian equivalent land mammal age in the latest Paleocene basal Sparnacian facies of Europe: Fauna, flora, paleoenvironment and (bio)stratigraphy
Smith, T.; Quesnel, F.; De Plöeg, G. et al

in PLoS ONE (2014), 9(1),

The Paleocene-Eocene Thermal Maximum (PETM) is correlated with the first occurrences of earliest modern mammals in the Northern Hemisphere. The latest Paleocene Clarkforkian North American Land Mammal Age ... [more ▼]

The Paleocene-Eocene Thermal Maximum (PETM) is correlated with the first occurrences of earliest modern mammals in the Northern Hemisphere. The latest Paleocene Clarkforkian North American Land Mammal Age, that has yielded rodents and carnivorans, is the only exception to this rule. However, until now no pre-PETM localities have yielded modern mammals in Europe or Asia. We report the first Clarkforkian equivalent Land Mammal Age in the latest Paleocene deposits of the basal Sparnacian facies at Rivecourt, in the north-central part of the Paris Basin. The new terrestrial vertebrate and macroflora assemblages are analyzed through a multidisciplinary study including sedimentologic, stratigraphic, isotopic, and palynological aspects in order to reconstruct the paleoenvironment and to evaluate biochronologic and paleogeographic implications. The mammals are moderately diverse and not abundant, contrary to turtles and champsosaurs. The macroflora is exceptional in preservation and diversity with numerous angiosperms represented by flowers, fruits, seeds and wood preserved as lignite material, revealing an abundance of Arecaceae, Betulaceae, Icacinaceae, Menispermaceae, Vitaceae and probably Cornaceae. Results indicate a Late Paleocene age based on carbon isotope data, palynology and vertebrate occurrences such as the choristoderan Champsosaurus, the arctocyonid Arctocyon , and the plesiadapid Plesiadapis tricuspidens. However, several mammal species compare better with the earliest Eocene. Among these, the particular louisinid Teilhardimys musculus, also recorded from the latest Paleocene of the Spanish Pyrenees, suggests a younger age than the typical MP6 reference level. Nevertheless, the most important aspect of the Rivecourt fauna is the presence of dental remains of a rodent and a "miacid" carnivoran, attesting to the presence of two modern mammalian orders in the latest Paleocene of Europe. Interestingly, these two groups are also the only modern groups recorded from the latest Paleocene of North America, making Rivecourt the first direct equivalent to the Clarkforkian Land Mammal Age outside of North America. © 2014 Smith et al. [less ▲]

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See detailCarbon Cycling of Lake Kivu (East Africa): Net Autotrophy in the Epilimnion and Emission of CO2 to the Atmosphere Sustained by Geogenic Inputs
Borges, Alberto ULg; Morana, C; Bouillon, S et al

in PLoS ONE (2014), 9(10), 109500

We report organic and inorganic carbon distributions and fluxes in a large (>2000 km2) oligotrophic, tropical lake (Lake Kivu, East Africa), acquired during four field surveys, that captured the seasonal ... [more ▼]

We report organic and inorganic carbon distributions and fluxes in a large (>2000 km2) oligotrophic, tropical lake (Lake Kivu, East Africa), acquired during four field surveys, that captured the seasonal variations (March 2007–mid rainy season, September 2007–late dry season, June 2008–early dry season, and April 2009–late rainy season). The partial pressure of CO2 (pCO2) in surface waters of the main basin of Lake Kivu showed modest spatial (coefficient of variation between 3% and 6%), and seasonal variations with an amplitude of 163 ppm (between 579±23 ppm on average in March 2007 and 742±28 ppm on average in September 2007). The most prominent spatial feature of the pCO2 distribution was the very high pCO2 values in Kabuno Bay (a small sub-basin with little connection to the main lake) ranging between 11213 ppm and 14213 ppm (between 18 and 26 times higher than in the main basin). Surface waters of the main basin of Lake Kivu were a net source of CO2 to the atmosphere at an average rate of 10.8 mmol m−2 d−1, which is lower than the global average reported for freshwater, saline, and volcanic lakes. In Kabuno Bay, the CO2 emission to the atmosphere was on average 500.7 mmol m−2 d−1 (~46 times higher than in the main basin). Based on whole-lake mass balance of dissolved inorganic carbon (DIC) bulk concentrations and of its stable carbon isotope composition, we show that the epilimnion of Lake Kivu was net autotrophic. This is due to the modest river inputs of organic carbon owing to the small ratio of catchment area to lake surface area (2.15). The carbon budget implies that the CO2 emission to the atmosphere must be sustained by DIC inputs of geogenic origin from deep geothermal springs. [less ▲]

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See detailGalectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer
Schulkens, Iris; Heusschen, Roy ULg; Van den boogaart, Vivianne et al

in PLoS ONE (2014)

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See detailEmbryonic Protein Undernutrition by Albumen Removal Programs the Hepatic Amino Acid and Glucose Metabolism during the Perinatal Period in an Avian Model.
Willems, Els; Hu, Tjing-Tjing; Soler Vasco, Laura et al

in PloS one (2014), 9(4), 94902

Different animal models have been used to study the effects of prenatal protein undernutrition and the mechanisms by which these occur. In mammals, the maternal diet is manipulated, exerting both direct ... [more ▼]

Different animal models have been used to study the effects of prenatal protein undernutrition and the mechanisms by which these occur. In mammals, the maternal diet is manipulated, exerting both direct nutritional and indirect hormonal effects. Chicken embryos develop independent from the hen in the egg. Therefore, in the chicken, the direct effects of protein deficiency by albumen removal early during incubation can be examined. Prenatal protein undernutrition was established in layer-type eggs by the partial replacement of albumen by saline at embryonic day 1 (albumen-deprived group), compared to a mock-treated sham and a non-treated control group. At hatch, survival of the albumen-deprived group was lower compared to the control and sham group due to increased early mortality by the manipulation. No treatment differences in yolk-free body weight or yolk weight could be detected. The water content of the yolk was reduced, whereas the water content of the carcass was increased in the albumen-deprived group, compared to the control group, indicating less uptake of nutrients from the yolk. At embryonic day 16, 20 and at hatch, plasma triiodothyronine (T3), corticosterone, lactate or glucose concentrations and hepatic glycogen content were not affected by treatment. At embryonic day 20, the plasma thyroxine (T4) concentrations of the albumen-deprived embryos was reduced compared to the control group, indicating a decreased metabolic rate. Screening for differential protein expression in the liver at hatch using two-dimensional difference gel electrophoresis revealed not only changed abundance of proteins important for amino acid metabolism, but also of enzymes related to energy and glucose metabolism. Interestingly, GLUT1, a glucose transporter, and PCK2 and FBP1, two out of three regulatory enzymes of the gluconeogenesis were dysregulated. No parallel differences in gene expressions causing the differences in protein abundance could be detected pointing to post-transcriptional or post-translational regulation of the observed differences. [less ▲]

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See detailEpidemiology of Visceral Leishmaniasis in Algeria: An Update
Adel, A; Boughoufalah, A; Saegerman, Claude ULg et al

in PLoS ONE (2014), 9(6), 99207

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See detailEnhanced or Reduced Fetal Growth Induced by Embryo Transfer into Smaller or Larger Breeds Alters Post-Natal Growth and Metabolism in Pre-Weaning Horses
Peugnet, Pauline; Wimel, Laurence; Duchamp, Guy et al

in PLoS ONE (2014), 9(7), 102044

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See detailProtected Areas in Tropical Africa: Assessing Threats and Conservation Activities
Tranquilli, Sandra; Abedi-Lartey, Michael; Abernethy, Katharine et al

in PLoS ONE (2014)

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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène ULg; Beguin, Yves ULg; Belle, Ludovic et al

in PLoS ONE (2014), (doi:10.1371), 113764

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic ... [more ▼]

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatment [less ▲]

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See detailStrategies for Using the Sheep Ovarian Cortex as a Model in Reproductive Medicine
Fransolet, Maïté ULg; Labied, Soraya ULg; Henry, Laurie ULg et al

in PLoS ONE (2014), 9(3), 91073

Objective: To evaluate and compare the distribution and density of primordial follicles within a whole sheep ovary and to gain insight into how to overcome the impact of natural follicular heterogeneity ... [more ▼]

Objective: To evaluate and compare the distribution and density of primordial follicles within a whole sheep ovary and to gain insight into how to overcome the impact of natural follicular heterogeneity on the experimental results. Design: Histological study. Setting: Academic research center. Animals: Five- to nine-month-old ewes. Interventions: Freshly sampled whole sheep ovaries were collected and prepared for histological analysis. Main Outcome Measure(s): The follicular densities and distributions were determined for hematoxylin and eosin sections. A mathematical model was derived based on the follicle counts and Monte-Carlo simulations. Results: Heterogeneous distributions and densities of primordial follicles were identified 1) for distinct areas of the same ovarian cortex, 2) between the ovaries of the same animal and 3) across different ewes. A mathematical model based on the analysis of 37,153 primordial follicles from 8 different ovaries facilitated the estimation of the number of cortical biopsies and sections that had to be analyzed to overcome such heterogeneity. Conclusion: The influence of physiological follicular heterogeneity on experimental and clinical results can be overcome when a definite number of cortical pieces and sections are taken into consideration. [less ▲]

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See detailDiscovering main genetic interactions with LABNet LAsso-based network inference.
Gadaleta, Francesco ULg; Van Steen, Kristel ULg

in PloS one (2014), 9(11), 110451

Genome-wide association studies can potentially unravel the mechanisms behind complex traits and common genetic diseases. Despite the valuable results produced thus far, many questions remain unanswered ... [more ▼]

Genome-wide association studies can potentially unravel the mechanisms behind complex traits and common genetic diseases. Despite the valuable results produced thus far, many questions remain unanswered. For instance, which specific genetic compounds are linked to the risk of the disease under investigation; what biological mechanism do they act through; or how do they interact with environmental and other external factors? The driving force of computational biology is the constantly growing amount of big data generated by high-throughput technologies. A practical framework that can deal with this abundance of information and that consent to discovering genetic associations and interactions is provided by means of networks. Unfortunately, high dimensionality, the presence of noise and the geometry of data can make the aforementioned problem extremely challenging. We propose a penalised linear regression approach that can deal with the aforementioned issues that affect genetic data. We analyse the gene expression profiles of individuals with a common trait to infer the network structure of interactions among genes. The permutation-based approach leads to more stable and reliable networks inferred from synthetic microarray data. We show that a higher number of permutations determines the number of predicted edges, improves the overall sensitivity and controls the number of false positives. [less ▲]

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See detailA comparison of multivariate genome-wide association methods.
Galesloot, Tessel E.; Van Steen, Kristel ULg; Kiemeney, Lambertus A. L. M. et al

in PloS one (2014), 9(4), 95923

Joint association analysis of multiple traits in a genome-wide association study (GWAS), i.e. a multivariate GWAS, offers several advantages over analyzing each trait in a separate GWAS. In this study we ... [more ▼]

Joint association analysis of multiple traits in a genome-wide association study (GWAS), i.e. a multivariate GWAS, offers several advantages over analyzing each trait in a separate GWAS. In this study we directly compared a number of multivariate GWAS methods using simulated data. We focused on six methods that are implemented in the software packages PLINK, SNPTEST, MultiPhen, BIMBAM, PCHAT and TATES, and also compared them to standard univariate GWAS, analysis of the first principal component of the traits, and meta-analysis of univariate results. We simulated data (N = 1000) for three quantitative traits and one bi-allelic quantitative trait locus (QTL), and varied the number of traits associated with the QTL (explained variance 0.1%), minor allele frequency of the QTL, residual correlation between the traits, and the sign of the correlation induced by the QTL relative to the residual correlation. We compared the power of the methods using empirically fixed significance thresholds (alpha = 0.05). Our results showed that the multivariate methods implemented in PLINK, SNPTEST, MultiPhen and BIMBAM performed best for the majority of the tested scenarios, with a notable increase in power for scenarios with an opposite sign of genetic and residual correlation. All multivariate analyses resulted in a higher power than univariate analyses, even when only one of the traits was associated with the QTL. Hence, use of multivariate GWAS methods can be recommended, even when genetic correlations between traits are weak. [less ▲]

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