Assessment of network module identification across complex diseases

Many bioinformatics methods have been proposed for reducing the complexity of large gene or protein networks into relevant subnetworks or modules. Yet, how such methods compare to each other in terms of their ability to identify disease-relevant modules in different types of network remains poorly understood. We launched the 'Disease Module Identification DREAM Challenge', an open competition to comprehensively assess module identification methods across diverse protein-protein interaction, signaling, gene co-expression, homology and cancer-gene networks. Predicted network modules were tested for association with complex traits and diseases using a unique collection of 180 genome-wide association studies. Our robust assessment of 75 module identification methods reveals top-performing algorithms, which recover complementary trait-associated modules. We find that most of these modules correspond to core disease-relevant pathways, which often comprise therapeutic targets. This community challenge establishes biologically interpretable benchmarks, tools and guidelines for molecular network analysis to study human disease biology

An international laboratory comparison of dissolved organic matter composition by high resolution mass spectrometry: Are we getting the same answer?

High-resolution mass spectrometry (HRMS) has become a vital tool for dissolved organic matter (DOM) characterization. The upward trend in HRMS analysis of DOM presents challenges in data comparison and interpretation among laboratories operating instruments with differing performance and user operating conditions. It is therefore essential that the community establishes metric ranges and compositional trends for data comparison with reference samples so that data can be robustly compared among research groups. To this end, four identically prepared DOM samples were each measured by 16 laboratories, using 17 commercially purchased instruments, using positive-ion and negative-ion mode electrospray ionization (ESI) HRMS analyses. The instruments identified ~1000 common ions in both negative- and positive-ion modes over a wide range of m/z values and chemical space, as determined by van Krevelen diagrams. Calculated metrics of abundance-weighted average indices (H/C, O/C, aromaticity, and m/z) of the commonly detected ions showed that hydrogen saturation and aromaticity were consistent for each reference sample across the instruments, while average mass and oxygenation were more affected by differences in instrument type and settings. In this paper we present 32 metric values for future benchmarking. The metric values were obtained for the four different parameters from four samples in two ionization modes and can be used in future work to evaluate the performance of HRMS instruments

Human pluripotent stem cell models of autism spectrum disorder:emerging frontiers, opportunities, and challenges towards neuronal networks in a dish

Autism spectrum disorder (ASD) is characterized by deficits in language development and social cognition and the manifestation of repetitive and restrictive behaviors. Despite recent major advances, our understanding of the pathophysiological mechanisms leading to ASD is limited. Although most ASD cases have unknown genetic underpinnings, animal and human cellular models of several rare, genetically defined syndromic forms of ASD have provided evidence for shared pathophysiological mechanisms that may extend to idiopathic cases. Here, we review our current knowledge of the genetic basis and molecular etiology of ASD and highlight how human pluripotent stem cell-based disease models have the potential to advance our understanding of molecular dysfunction. We summarize landmark studies in which neuronal cell populations generated from human embryonic stem cells and patient-derived induced pluripotent stem cells have served to model disease mechanisms, and we discuss recent technological advances that may ultimately allow in vitro modeling of specific human neuronal circuitry dysfunction in ASD. We propose that these advances now offer an unprecedented opportunity to help better understand ASD pathophysiology. This should ultimately enable the development of cellular models for ASD, allowing drug screening and the identification of molecular biomarkers for patient stratification

Enhanced tunability of magneto-impedance and magneto-capacitance in annealed Metglas/PZT magnetoelectric composites

This report is on a new class of magnetostatically tunable magneto-impedance and magneto-capacitance devices based on a composite of ferromagnetic Metglas and ferroelectric lead zirconate titanate (PZT). Layered magneto-electric (ME) composites with annealed Metglas and PZT were studied in a longitudinal in-plane magnetic field-transverse electric field (L-T) mode. It was found that the degree of tunability was dependent on the annealing temperature of Metglas. An impedance tunability (ΔZ/Z0) of ≥400% was obtained at the electromechanical resonance (EMR) frequency (fr) for a sample with Metglas layers annealed at Ta = 500oC. This tunability is a factor of two higher than for composites with Metglas annealed at 350oC. The tunability of the capacitance, (ΔC/C0), was found to be 290% and -135k% at resonance and antiresonance, respectively, for Ta = 500oC. These results provide clear evidence for improvement in static magnetic field tunability of impedance and capacitance of ME composites with the use of annealed Metglas and are of importance for their potential use in tunable electronic applications

Self-biased magnetoelectric gyrators in composite of samarium substituted nickel zinc ferrites and piezoelectric ceramics

Magnetoelectric (ME) gyrators consisting of system of Sm-doped NiZn ferrites (Ni1-xZnxSm0.02Fe1.98O4, 0.2≤x≤0.5) and piezoelectric ceramics [Pb(Zr, Ti)O3] with coil wound around have been developed. Distinct hysteresis behaviors were observed in off-resonance ME couplings and power conversion efficiency (PE) characterizations, resulting in a non-zero ME response and anticipating a higher remanent PE at zero bias. Consequently, light samarium doping facilitates the enhancement of PE, which reaches its maximum of 81.5% under optimum bias and self-biasing value of 58.5% under zero bias in the composite of Ni0.8Zn0.2Sm0.02Fe1.98O4/PZT trilayer respectively, exhibiting approximately 2.2 times higher than the counterpart without any samarium doping. These findings provide great possibilities of ME gyrators for miniaturized devices deployed in power electronics, converters and wireless energy harvesters without a sacrifice in magneto-mechanical efficiency

Dimension Effects of a Magnetoelectric Gyrator with FeCoSiB/Pb(Zr,Ti)O3 Layered Composites Core for Efficient Power Conversion

International audienc

Tumor cell nuclei soften during transendothelial migration

During cancer metastasis, tumor cells undergo significant deformation in order to traverse through endothelial cell junctions in the walls of blood vessels. As cells pass through narrow gaps, smaller than the nuclear diameter, the spatial configuration of chromatin must change along with the distribution of nuclear enzymes. Nuclear stiffness is an important determinant of the ability of cells to undergo transendothelial migration, yet no studies have been conducted to assess whether tumor cell cytoskeletal or nuclear stiffness changes during this critical process in order to facilitate passage. To address this question, we employed two non-contact methods, Brillouin confocal microscopy (BCM) and confocal reflectance quantitative phase microscopy (QPM), to track the changes in mechanical properties of live, transmigrating tumor cells in an in vitro collagen gel platform. Using these two imaging modalities to study transmigrating MDA-MB-231, A549, and A375 cells, we found that both the cells and their nuclei soften upon extravasation and that the nuclear membranes remain soft for at least 24 h. These new data suggest that tumor cells adjust their mechanical properties in order to facilitate extravasation