A Robust and Accurate Method for Feature Selection and Prioritization from Multi-Class OMICs Data

Selecting relevant features is a common task in most OMICs data analysis, where the aim is to identify a small set of key features to be used as biomarkers. To this end, two alternative but equally valid methods are mainly available, namely the univariate (filter) or the multivariate (wrapper) approach. The stability of the selected lists of features is an often neglected but very important requirement. If the same features are selected in multiple independent iterations, they more likely are reliable biomarkers. In this study, we developed and evaluated the performance of a novel method for feature selection and prioritization, aiming at generating robust and stable sets of features with high predictive power. The proposed method uses the fuzzy logic for a first unbiased feature selection and a Random Forest built from conditional inference trees to prioritize the candidate discriminant features. Analyzing several multi-class gene expression microarray data sets, we demonstrate that our technique provides equal or better classification performance and a greater stability as compared to other Random Forest-based feature selection methods.     

Newborn Body Fat: Associations with Maternal Metabolic State and Placental Size

Background

Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight.

Methods

The present work was performed in a subcohort (n = 207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30–32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes.

Results

Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates.

Conclusion

Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI-related metabolic factors on fetal fat accretion to a significant extent act by modifying placental weight.     

A comprehensive analysis of common copy-number variations in the human genome

Segmental copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component of our phenotypic diversity. In this study, using a whole-genome array comparative genomic hybridization assay, we identified 3,654 autosomal segmental CNVs, 800 of which appeared at a frequency of at least 3%. Of these frequent CNVs, 77% are novel. In the 95 individuals analyzed, the two most diverse genomes differed by at least 9 Mb in size or varied by at least 266 loci in content. Approximately 68% of the 800 polymorphic regions overlap with genes, which may reflect human diversity in senses (smell, hearing, taste, and sight), rhesus phenotype, metabolism, and disease susceptibility. Intriguingly, 14 polymorphic regions harbor 21 of the known human microRNAs, raising the possibility of the contribution of microRNAs to phenotypic diversity in humans. This in-depth survey of CNVs across the human genome provides a valuable baseline for studies involving human genetics.     

Comparing sensibility for touch,cold, and warmth in different skin areas

The primary objective of this pilot study was to assess if the magnitude estimation of suprathreshold brushing, warmth (40?°C), and cold (25?°C) stimuli of the skin over the dorsum of the hand and the dorsum of the foot are comparable to the perceived intensity for the same stimuli applied to the skin over any of the following areas: forehead, m. trapezius, m. deltoideus, thoracic back, and lumbar back, respectively. Thirty-two subjects aged 18–64 years were included. Participants were examined by two physicians on two different occasions, 1–58 days apart. Participants rated the magnitude of the perceived sensation of each stimulus on an 11-point numerical rating scale (NRS) 0–10, where 0 was anchored to “no sensation at all for touch/cold/warmth” and 10 anchored to “the most intense imaginable non-painful sensation of touch/cold/warmth”. The criterion for sensory equivalence for one modality was arbitrarily considered satisfactory if two regions had the same numerical rating ±1 point in at least 85% of the individuals. Based on the pre-study criteria for sensory equivalence applied in this study only one area was found to be equivalent to the foot skin for the percept of brushing, that is, the skin over the deltoid muscle and one area for the hand, that is, the skin over the forehead. We failed to find any area with equivalent sensitivity to the hand or the foot for the cold or warm stimuli.     

Glutathione transferases catalyze recycling of auto‐toxic cyanogenic glucosides in sorghum

Cyanogenic glucosides are nitrogen‐containing specialized metabolites that provide chemical defense against herbivores and pathogens via the release of toxic hydrogen cyanide. It has been suggested that cyanogenic glucosides are also a store of nitrogen that can be remobilized for general metabolism via a previously unknown pathway. Here we reveal a recycling pathway for the cyanogenic glucoside dhurrin in sorghum (Sorghum bicolor) that avoids hydrogen cyanide formation. As demonstrated in vitro, the pathway proceeds via spontaneous formation of a dhurrin‐derived glutathione conjugate, which undergoes reductive cleavage by glutathione transferases of the plant‐specific lambda class (GSTLs) to produce p‐hydroxyphenyl acetonitrile. This is further metabolized to p‐hydroxyphenylacetic acid and free ammonia by nitrilases, and then glucosylated to form p‐glucosyloxyphenylacetic acid. Two of the four GSTLs in sorghum exhibited high stereospecific catalytic activity towards the glutathione conjugate, and form a subclade in a phylogenetic tree of GSTLs in higher plants. The expression of the corresponding two GSTLs co‐localized with expression of the genes encoding the p‐hydroxyphenyl acetonitrile‐metabolizing nitrilases at the cellular level. The elucidation of this pathway places GSTs as key players in a remarkable scheme for metabolic plasticity allowing plants to reverse the resource flow between general and specialized metabolism in actively growing tissue.     

Benthic bacterial and fungal productivity and carbon turnover in a freshwater marsh

Heterotrophic bacteria and fungi are widely recognized as crucial mediators of carbon, nutrient, and energy flow in ecosystems, yet information on their total annual production in benthic habitats is lacking. To assess the significance of annual microbial production in a structurally complex system, we measured production rates of bacteria and fungi over an annual cycle in four aerobic habitats of a littoral freshwater marsh. Production rates of fungi in plant litter were substantial (0.2 to 2.4 mg C g(-1) C) but were clearly outweighed by those of bacteria (2.6 to 18.8 mg C g(-1) C) throughout the year. This indicates that bacteria represent the most actively growing microorganisms on marsh plant litter in submerged conditions, a finding that contrasts strikingly with results from both standing dead shoots of marsh plants and submerged plant litter decaying in streams. Concomitant measurements of microbial respiration (1.5 to 15.3 mg C-CO2 g(-1) of plant litter C day(-1)) point to high microbial growth efficiencies on the plant litter, averaging 45.5%. The submerged plant litter layer together with the thin aerobic sediment layer underneath (average depth of 5 mm) contributed the bulk of microbial production per square meter of marsh surface (99%), whereas bacterial production in the marsh water column and epiphytic biofilms was negligible. The magnitude of the combined production in these compartments (approximately 1,490 g C m(-2) year(-1)) highlights the importance of carbon flows through microbial biomass, to the extent that even massive primary productivity of the marsh plants (603 g C m(-2) year(-1)) and subsidiary carbon sources (approximately 330 g C m(-2) year(-1)) were insufficient to meet the microbial carbon demand. These findings suggest that littoral freshwater marshes are genuine hot spots of aerobic microbial carbon transformations, which may act as net organic carbon importers from adjacent systems and, in turn, emit large amounts of CO2 (here, approximately 870 g C m(-2) year(-1)) into the atmosphere.     

Urea in Weaver Ant Feces: Quantification and Investigation of the Uptake and Translocation of Urea in <Emphasis Type="Italic">Coffea arabica</Emphasis>

Weaver ants are tropical insects that nest in tree canopies, and for centuries these ants have been used for pest control in tropical orchards. Trees hosting weaver ants might benefit not only from the pest protective properties of these insects but also an additional supply of nutrients from ant feces deposited on the leaves. In a recent study, we demonstrated that Coffea arabica plants hosting Oecophylla smaragdina weaver ants under laboratory conditions experienced enhanced nitrogen availability compared with plants grown without ants. Therefore, the aim of the present study was to further investigate the interactions of weaver ants with the host plants with respect to plant nutrition. Here, we report the identification and quantification of urea, a highly effective foliar nutrient present in the fecal depositions of O. smaragdina. Feces samples obtained from six O. smaragdina colonies were analyzed, and urea concentrations ranging from 1.98 to 31.05 μg/mg ant feces were detected. Subsequently, we investigated the uptake and translocation of ¹⁵N₂-urea in amounts corresponding to the estimated urea contribution via feces depositions on single host plant leaves under laboratory conditions. The results clearly demonstrated that fecal urea was not only assimilated but also translocated within the plant. This evidence strongly supports the hypothesis that the fecal urea of weaver ants is a source of nitrogen for the host trees. Thus, weaver ant feces likely contribute to an improved nutritional status of ant-hosting trees in tropical orchards, thereby adding value to the use of weaver ants for the biocontrol of insect pests.     

Evaluation of HPV Infection and Smoking Status Impacts on Cell Proliferation in Epithelial Layers of Cervical Neoplasia

Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n = 196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n = 261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ≥50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy.