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See detailWhat do Pneumocystis organisms tell us about the phylogeography of their hosts? The case of the woodmouse Apodemus sylvaticus in continental Europe and western Mediterranean islands
Demanche, christine; Deville, Manjula; Michaux, Johan ULg et al

in PLoS ONE (in press)

Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the ... [more ▼]

Pneumocystis fungi represent a highly diversified biological group with numerous species, which display a strong host-specificity suggesting a long co-speciation process. In the present study, the presence and genetic diversity of Pneumocystis organisms was investigated in 203 lung samples from woodmice (Apodemus sylvaticus) collected on western continental Europe and Mediterranean islands. The presence of Pneumocystis DNA was assessed by nested PCR at both large and small mitochondrial subunit (mtLSU and mtSSU) rRNA loci. Direct sequencing of nested PCR products demonstrated a very high variability among woodmouse-derived Pneumocystis organisms with a total number of 30 distinct combined mtLSU and mtSSU sequence types. However, the genetic divergence among these sequence types was very low (up to 3.87%) and the presence of several Pneumocystis species within Apodemus sylvaticus was considered unlikely. The analysis of the genetic structure of woodmouse-derived Pneumocystis revealed two distinct groups. The first one comprised Pneumocystis from woodmice collected in continental Spain, France and Balearic islands. The second one included Pneumocystis from woodmice collected in continental Italy, Corsica and Sicily. These two genetic groups were in accordance with the two lineages currently described within the host species Apodemus sylvaticus. Pneumocystis organisms are emerging as powerful tools for phylogeographic studies in mammals [less ▲]

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See detailRetirement age and the age of onset of Alzheimer’s disease: Results from the ICTUS study
Grotz, Catherine ULg; Letenneur, Luc; Bonsang, Eric ULg et al

in PLoS ONE (2015)

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See detailTime-varying respiratory system elastance: a physiological model for patients who are spontaneously breathing.
Chiew, Yeong Shiong; Pretty, Christopher; Docherty, Paul D. et al

in PloS one (2015), 10(1), 0114847

BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no ... [more ▼]

BACKGROUND: Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (Edrs) model that can be used in spontaneously breathing patients to determine their respiratory mechanics. METHODS: A time-varying respiratory elastance model is developed with a negative elastic component (Edemand), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. Edrs of every breathing cycle for each patient at different ventilation modes are presented for comparison. RESULTS: At the start of every breathing cycle initiated by patient, Edrs is < 0. This negativity is attributed from the Edemand due to a positive lung volume intake at through negative pressure in the lung compartment. The mapping of Edrs trajectories was able to give unique information to patients' breathing variability under different ventilation modes. The area under the curve of Edrs (AUCEdrs) for most patients is > 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator. CONCLUSION: The Edrs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes. [less ▲]

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See detailThe aerodynamic cost of head morphology in bats: maybe not as bad as it seems
Vanderelst, Dieter; Peremans, Herbert; Abdul Razak, Norizham et al

in PLoS ONE (2015), 10(3), 0118545

At first sight, echolocating bats face a difficult trade-off. As flying animals, they would benefit from a streamlined geometric shape to reduce aerodynamic drag and increase flight efficiency. However ... [more ▼]

At first sight, echolocating bats face a difficult trade-off. As flying animals, they would benefit from a streamlined geometric shape to reduce aerodynamic drag and increase flight efficiency. However, as echolocating animals, their pinnae generate the acoustic cues necessary for navigation and foraging. Moreover, species emitting sound through their nostrils often feature elaborate noseleaves that help in focussing the emitted echolocation pulses. Both pinnae and noseleaves reduce the streamlined character of a bat’s morphology. It is generally assumed that by compromising the streamlined charactered of the geometry, the head morphology generates substantial drag, thereby reducing flight efficiency. In contrast, it has also been suggested that the pinnae of bats generate lift forces counteracting the detrimental effect of the increased drag. However, very little data exist on the aerodynamic properties of bat pinnae and noseleaves. In this work, the aerodynamic forces generated by the heads of seven species of bats, including noseleaved bats, are measured by testing detailed 3D models in a wind tunnel. Models of Myotis daubentonii, Macrophyllum macrophyllum, Micronycteris microtis, Eptesicus fuscus, Rhinolophus formosae, Rhinolophus rouxi and Phyllostomus discolor are tested. The results confirm that non-streamlined facial morphologies yield considerable drag forces but also generate substantial lift. The net effect is a slight increase in the lift-to-drag ratio. Therefore, there is no evidence of high aerodynamic costs associated with the morphology of bat heads [less ▲]

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See detailBacterial Community Composition in Three Freshwater Reservoirs of Different Alkalinity and Trophic Status
Llirós, Marc; Inceoğlu, Özgul; García-Armisen, Tamara et al

in PLoS ONE (2014)

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See detailFirst Evidence of a Volatile Sex Pheromone in Lady Beetles
Fassotte, Bérénice ULg; Fischer, Christophe ULg; Durieux, Delphine ULg et al

in PLoS ONE (2014)

To date, volatile sex pheromones have not been identified in the Coccinellidae family; yet, various studies have suggested that such semiochemicals exist. Here, we collected volatile chemicals released by ... [more ▼]

To date, volatile sex pheromones have not been identified in the Coccinellidae family; yet, various studies have suggested that such semiochemicals exist. Here, we collected volatile chemicals released by virgin females of the multicolored Asian lady beetle, Harmonia axyridis (Pallas), which were either allowed or not allowed to feed on aphids. Virgin females in the presence of aphids, exhibited “calling behavior”, which is commonly associated with the emission of a sex pheromone in several Coleoptera species. These calling females were found to release a blend of volatile compounds that is involved in the remote attraction (i.e., from a distance) of males. Gas Chromatography-Mass Spectrometry (GC-MS) analyses revealed that (–)-β-caryophyllene was the major constituent of the volatile blend (ranging from 80 to 86%), with four other chemical components also being present; β-elemene, methyl-eugenol, α-humulene, and α-bulnesene. In a second set of experiments, the emission of the five constituents identified from the blend was quantified daily over a 9-day period after exposure to aphids. We found that the quantity of all five chemicals significantly increased across the experimental period. Finally, we evaluated the activity of a synthetic blend of these chemicals by performing bioassays which demonstrated the same attractive effect in males only. The results confirm that female H. axyridis produce a volatile sex pheromone. These findings have potential in the development of more specific and efficient biological pest-control management methods aimed at manipulating the behavior of this invasive lady beetle. [less ▲]

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See detailRGD surface functionalization of the hydrophilic acrylic intraocular lens material to control posterior capsular opacification
Huang, Yi-Shiang ULg; Bertrand, Virginie ULg; Bozukova, Dimitriya et al

in PLoS ONE (2014), 9(12), 32

Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal ... [more ▼]

Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patient’s age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development. [less ▲]

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See detailSoil charcoal to assess the impacts of past human disturbances on tropical forests
Vleminckx, Jason; Morin-Rivat, Julie ULg; Biwolé, Achille et al

in PLoS ONE (2014)

The canopy of many central African forests is dominated by light-demanding tree species that do not regenerate well under themselves. The prevalence of these species might result from ancient slash-and ... [more ▼]

The canopy of many central African forests is dominated by light-demanding tree species that do not regenerate well under themselves. The prevalence of these species might result from ancient slash-and-burn agricultural activities that created large openings, while a decline of these activities since the colonial period could explain their deficit of regeneration. To verify this hypothesis, we compared soil charcoal abundance, used as a proxy for past slash-and-burn agriculture, and tree species composition assessed on 208 rainforest 0.2 ha plots located in three areas from Southern Cameroon. Species were classified in regeneration guilds (pioneer, non-pioneer light-demanding, shade-bearer) and characterized by their woodspecific gravity, assumed to reflect light requirement. We tested the correlation between soil charcoal abundance and: (i) the relative abundance of each guild, (ii) each species and family abundance and (iii) mean wood-specific gravity. Charcoal was found in 83% of the plots, indicating frequent past forest fires. Radiocarbon dating revealed two periods of fires: ‘‘recent’’ charcoal were on average 300 years old (up to 860 BP, n = 16) and occurred in the uppermost 20 cm soil layer, while ‘‘ancient’’ charcoal were on average 1900 years old (range: 1500 to 2800 BP, n = 43, excluding one sample dated 9400 BP), and found in all soil layers. While we expected a positive correlation between the relative abundance of light demanding species and charcoal abundance in the upper soil layer, overall there was no evidence that the current heterogeneity in tree species composition can be explained by charcoal abundance in any soil layer. The absence of signal supporting our hypothesis might result from (i) a relatively uniform impact of past slash-and-burn activities, (ii) pedoturbation processes bringing ancient charcoal to the upper soil layer, blurring the signal of centuries-old Human disturbances, or (iii) the prevalence of other environmental factors on species composition. [less ▲]

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See detailComparison of the Decomposition VOC Profile during Winter and Summer in a Moist, Mid-latitude (Cfb) Climate
Forbes, Shari L.; Perrault, Katelynn A.; Stefanuto, Pierre-Hugues ULg et al

in PLoS ONE (2014), 9(e113681), 1-11

The investigation of volatile organic compounds (VOCs) associated with decomposition is an emerging field in forensic taphonomy due to their importance in locating human remains using biological detectors ... [more ▼]

The investigation of volatile organic compounds (VOCs) associated with decomposition is an emerging field in forensic taphonomy due to their importance in locating human remains using biological detectors such as insects and canines. A consistent decomposition VOC profile has not yet been elucidated due to the intrinsic impact of the environment on the decomposition process in different climatic zones. The study of decomposition VOCs has typically occurred during the warmer months to enable chemical profiling of all decomposition stages. The present study investigated the decomposition VOC profile in air during both warmer and cooler months in a moist, mid-latitude (Cfb) climate as decomposition occurs year-round in this environment. Pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface to decompose naturally and their VOC profile was monitored during the winter and summer months. Corresponding control sites were also monitored to determine the natural VOC profile of the surrounding soil and vegetation. VOC samples were collected onto sorbent tubes and analyzed using comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (GC6GC-TOFMS). The summer months were characterized by higher temperatures and solar radiation, greater rainfall accumulation, and comparable humidity when compared to the winter months. The rate of decomposition was faster and the number and abundance of VOCs was proportionally higher in summer. However, a similar trend was observed in winter and summer demonstrating a rapid increase in VOC abundance during active decay with a second increase in abundance occurring later in the decomposition process. Sulfur-containing compounds, alcohols and ketones represented the most abundant classes of compounds in both seasons, although almost all 10 compound classes identified contributed to discriminating the stages of decomposition throughout both seasons. The advantages of GC6GC-TOFMS were demonstrated for detecting and identifying trace levels of VOCs, particularly ethers, which are rarely reported as decomposition VOCs. [less ▲]

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See detailQTL analysis and candidate gene mapping for the polyphenol content in cider apple
Verdu, Cindy ULg; Guyot, Sylvain; Childebrand, Nicolas et al

in PLoS ONE (2014), 9(10), 107103

Polyphenols have favorable antioxidant potential on human health suggesting that their high content is responsible for the beneficial effects of apple consumption. They control the quality of ciders as ... [more ▼]

Polyphenols have favorable antioxidant potential on human health suggesting that their high content is responsible for the beneficial effects of apple consumption. They control the quality of ciders as they predominantly account for astringency, bitterness, color and aroma. In this study, we identified QTLs controlling phenolic compound concentrations and the average polymerization degree of flavanols in a cider apple progeny. Thirty two compounds belonging to five groups of phenolic compounds were identified and quantified by reversed phase liquid chromatography on both fruit extract and juice, over three years. The average polymerization degree of flavanols was estimated in fruit by phloroglucinolysis coupled to HPLC. Parental maps were built using SSR and SNP markers and used for the QTL analysis. Sixty-nine and 72 QTLs were detected on 14 and 11 linkage groups of the female and male maps, respectively. A majority of the QTLs identified in this study are specific to this population, while others are consistent with previous studies. This study presents for the first time in apple, QTLs for the mean polymerization degree of procyanidins, for which the mechanisms involved remains unknown to this day. Identification of candidate genes underlying major QTLs was then performed in silico and permitted the identification of 18 enzymes of the polyphenol pathway and six transcription factors involved in the apple anthocyanin regulation. New markers were designed from sequences of the most interesting candidate genes in order to confirm their co-localization with underlying QTLs by genetic mapping. Finally, the potential use of these QTLs in breeding programs is discussed. [less ▲]

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See detailPosterior Cingulate Cortex-Related Co-Activation Patterns: A Resting State fMRI Study in Propofol-Induced Loss of Consciousness
Amico, Enrico ULg; Gomez, Francisco; Di Perri, Carol et al

in PLoS ONE (2014), 9

Background: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating ... [more ▼]

Background: Recent studies have been shown that functional connectivity of cerebral areas is not a static phenomenon, but exhibits spontaneous fluctuations over time. There is evidence that fluctuating connectivity is an intrinsic phenomenon of brain dynamics that persists during anesthesia. Lately, point process analysis applied on functional data has revealed that much of the information regarding brain connectivity is contained in a fraction of critical time points of a resting state dataset. In the present study we want to extend this methodology for the investigation of resting state fMRI spatial pattern changes during propofol-induced modulation of consciousness, with the aim of extracting new insights on brain networks consciousness-dependent fluctuations. Methods: Resting-state fMRI volumes on 18 healthy subjects were acquired in four clinical states during propofol injection: wakefulness, sedation, unconsciousness, and recovery. The dataset was reduced to a spatio-temporal point process by selecting time points in the Posterior Cingulate Cortex (PCC) at which the signal is higher than a given threshold (i.e., BOLD intensity above 1 standard deviation). Spatial clustering on the PCC time frames extracted was then performed (number of clusters = 8), to obtain 8 different PCC co-activation patterns (CAPs) for each level of consciousness. Results: The current analysis shows that the core of the PCC-CAPs throughout consciousness modulation seems to be preserved. Nonetheless, this methodology enables to differentiate region-specific propofol-induced reductions in PCC-CAPs, some of them already present in the functional connectivity literature (e.g., disconnections of the prefrontal cortex, thalamus, auditory cortex), some others new (e.g., reduced co-activation in motor cortex and visual area). Conclusion: In conclusion, our results indicate that the employed methodology can help in improving and refining the characterization of local functional changes in the brain associated to propofol-induced modulation of consciousness. [less ▲]

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See detailThe Transcription Factor EGR1 Localizes to the Nucleolus and Is Linked to Suppression of Ribosomal Precursor Synthesis
Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa et al

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

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the ... [more ▼]

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism. [less ▲]

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See detailNest grouping patterns of bonobos (Pan paniscus) in relation to fruit availability in a forest-savannah mosaic
Serckx, Adeline ULg; Huynen, Marie-Claude ULg; Bastin, Jean-François ULg et al

in PLoS ONE (2014)

A topic of major interest in socio-ecology is the comparison of chimpanzees and bonobos’ grouping patterns. Numerous studies have highlighted the impact of social and environmental factors on the ... [more ▼]

A topic of major interest in socio-ecology is the comparison of chimpanzees and bonobos’ grouping patterns. Numerous studies have highlighted the impact of social and environmental factors on the different evolution in group cohesion seen in these sister species. We are still lacking, however, key information about bonobo social traits across their habitat range, in order to make accurate inter-species comparisons. In this study we investigated bonobo social cohesiveness at nesting sites depending on fruit availability in the forest-savannah mosaic of western Democratic Republic of Congo (DRC), a bonobo habitat which has received little attention from researchers and is characterized by high food resource variation within years. We collected data on two bonobo communities. Nest counts at nesting sites were used as a proxy for night grouping patterns and were analysed with regard to fruit availability. We also modelled bonobo population density at the site in order to investigate yearly variation. We found that one community density varied across the three years of surveys, suggesting that this bonobo community has significant variability in use of its home range. This finding highlights the importance of forest connectivity, a likely prerequisite for the ability of bonobos to adapt their ranging patterns to fruit availability changes. We found no influence of overall fruit availability on bonobo cohesiveness. Only fruit availability at the nesting sites showed a positive influence, indicating that bonobos favour food ‘hot spots’ as sleeping sites. Our findings have confirmed the results obtained from previous studies carried out in the dense tropical forests of DRC. Nevertheless, in order to clarify the impact of environmental variability on bonobo social cohesiveness, we will need to make direct observations of the apes in the forest-savannah mosaic as well as make comparisons across the entirety of the bonobos’ range using systematic methodology. [less ▲]

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See detailExploiting SNP Correlations within Random Forest for Genome-Wide Association Studies
Botta, Vincent ULg; Louppe, Gilles ULg; Geurts, Pierre ULg et al

in PLoS ONE (2014)

The primary goal of genome-wide association studies (GWAS) is to discover variants that could lead, in isolation or in combination, to a particular trait or disease. Standard approaches to GWAS, however ... [more ▼]

The primary goal of genome-wide association studies (GWAS) is to discover variants that could lead, in isolation or in combination, to a particular trait or disease. Standard approaches to GWAS, however, are usually based on univariate hypothesis tests and therefore can account neither for correlations due to linkage disequilibrium nor for combinations of several markers. To discover and leverage such potential multivariate interactions, we propose in this work an extension of the Random Forest algorithm tailored for structured GWAS data. In terms of risk prediction, we show empirically on several GWAS datasets that the proposed T-Trees method significantly outperforms both the original Random Forest algorithm and standard linear models, thereby suggesting the actual existence of multivariate non-linear effects due to the combinations of several SNPs. We also demonstrate that variable importances as derived from our method can help identify relevant loci. Finally, we highlight the strong impact that quality control procedures may have, both in terms of predictive power and loci identification. [less ▲]

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See detailWidespread occurence of expressed fungal secretory peroxydases in forest soils
Kellner, Harald; Luis, Patricia; Pecyna, Marek, J. et al

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

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See detailInfluence of noise correction on intra- and inter-subject variability of quantitative metrics in diffusion kurtosis imaging
André, Elodie ULg; Grinberg, Farida; Farrher, Ezequiel et al

in PLoS ONE (2014)

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing ... [more ▼]

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing number of studies, DKI has a potential to establish itself as a valuable tool in brain diagnostics. However, to become a routine procedure, DKI still needs to be improved in terms of robustness, reliability, and reproducibility. As it requires acquisitions at higher diffusion31 weightings, results are more affected by noise than in diffusion tensor imaging. The lack of standard procedures for post-processing, especially for noise correction, might become a significant obstacle for the use of DKI in clinical routine limiting its application. We considered two noise correction schemes accounting for the noise properties of multichannel phased-array coils, in order to improve the data quality at signal-to-noise ratio (SNR) typical for DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise correction approaches in Monte Carlo simulations and in in vivo human studies. The intra-subject reproducibility is investigated in a single subject study by varying the SNR level and SNR spatial distribution. Then the impact of the noise correction on inter-subject variability is evaluated in a homogeneous sample of 25 healthy volunteers. Results show a strong impact of noise correction on the MK estimate, while the estimation of FA and MD was affected to a lesser extent. Both intra- and inter-subject SNR related variability of the MK estimate is considerably reduced after correction for the noise bias, providing more accurate and reproducible measures. In this work, we have proposed a straightforward method that improves accuracy of DKI metrics. This should contribute to standardization of DKI applications in clinical studies and making valuable inferences in group analysis and longitudinal studies. [less ▲]

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See detailNIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms
Ruyssinck, Joeri; Huynh-Thu, Vân Anh ULg; Geurts, Pierre ULg et al

in PLoS ONE (2014)

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts ... [more ▼]

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available. [less ▲]

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See detailCXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation
Glauzy, Salomé; André-Schmutz, I; Larghero, J et al

in PLoS ONE (2014), 9(3), 91492

Detailed reference viewed: 6 (1 ULg)