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PhenoExplorer: An Interactive Web-based Platform for Exploring (Epi)Genome-Wide Associations Using a Swiss Population-based Study
The recent advent of high-throughput sequencing technologies has allowed exploring the contribution of thousands of genomic, epigenomic, transcriptomic, or proteomic variants to complex phenotypic traits. Here, we sought to conduct large-scale (Epi)Genome-Wide Association Studies (GWAS/EWAS) to investigate the associations between genomic (Single Nucleotide Polymorphism; SNP) and epigenomic (Cytosine-Phospho-Guanine; CpG) markers, with multiple phenotypic traits in a population-based context. We used data from SKIPOGH, a family- and population-based cohort conducted in the cities of Lausanne, Geneva, and Bern (N=1100). We used 7,577,572 SNPs, 420,444 CpGs, and 825 phenotypes, including anthropometric, clinical, blood, urine, metabolite, and metal measures. GWAS analyses assessed the associations between SNPs and metabolites and metals (N=279), using regression models adjusted for age, sex, recruitment center, and familial structure, whereas EWAS analyses explored the relations between CpGs and 825 phenotypes, additionally adjusting for the seasonality of blood sampling and technical nuisance. Following the implementation of GWAS and EWAS analyses, we developed a web-based platform, PhenoExplorer, aimed at providing an open access to the obtained results. Of the 279 phenotypes included in GWAS, 103 displayed significant associations with 2804 SNPs (2091 unique SNPs) at Bonferroni threshold, whereas 109 of the 825 phenotypes included in EWAS analyses were associated with 4893 CpGs (2578 unique CpGs). All of the obtained GWAS and EWAS results were eventually made available using the in-house built web-based PhenoExplorer platform, with the purpose of providing an open-access to the tested associations. In conclusion, we provide a comprehensive outline of GWAS and EWAS associations performed in a Swiss population-based study. Further, we set up a web-based PhenoExplorer platform with the purpose of contributing to the overall understanding of the role of molecular variants in regulating complex phenotypes
(Anti)viral Material Design Guided by Scattering Methods
Viruses are nature’s own nanoparticles that are highly symmetric and monodisperse in size and shape with well-defined surface chemistry. They have evolved for optimal cell interactions, genetic information delivery and replication by the host cell over millions of years. These features render them into very efficient pathogens that place a severe burden onto the health of our society. At the same time, they are highly interesting objects for colloidal studies and building blocks for advanced bio-inspired materials for health applications. Their characterisation requires sophisticated experimental techniques such as scattering of X-rays, neutrons, and light to probe structures and interactions from the nanometre to the micrometre length-scale in solution. This contribution summarizes the recent progress in the field of virus self-assembly and virus-based biopolymer composites for advanced material design. It discusses the advances and highlights some of the challenges in the characterization of structure and dynamics in these materials with a focus on scattering techniques. It further demonstrates selected applications in the field of food and water purification
Novel Insights on the Three-dimensional Shape of Microgels at Fluid Interfaces
Mechanically soft colloids (microgels) adsorbed at the interface between two fluids offer superior advantages over hard counterparts for a variety of applications ranging from foams/emulsion stabilization to the assembly of two-dimensional (2D) materials. Particle deformability and compressibility impart additional responses to microgel-laden interfaces that can be controlled on-demand by varying single-particle properties (e.g. crosslinking content and polymer density profile) and/or external parameters (e.g. interfacial compression and tension, temperature, oil polarity). In order to understand how single-particle softness influences the resulting material properties, a detailed quantification of the microgel’s 3D conformation when confined at the fluid interface is of utmost importance. This article describes how different methodologies can be used to visualize, and in some case quantify, the conformation of adsorbed microgels, putting particular emphasis on the multiple advantages offered by in situ atomic force microscopy imaging at the fluid interface. The influence of the internal particle architecture, as well as that of temperature, interfacial tension and solubility in the organic phase, will be discussed. Finally, some perspectives on how softness can be exploited to tune the structural and mechanical properties of microgel monolayers will be provided
Polymer Colloids: Moving beyond Spherical Particles
When thinking about colloidal particles, the fist image that comes into mind is that of tiny little polystyrene spheres with a narrow size distribution. While spherical polymer colloids are one of the workhorses of colloid science, scientists have been working on the development of progressively advanced strategies to move beyond particles with spherical shapes, and prepared polymer colloids with more complex morphologies. This short review aims at providing a summary of these developments, focusing primarily on methods applicable to submicron particles, with an eye towards their applications and some discussion about advantages and drawbacks of the various approaches
Noble Gas Mass Spectrometry in Earth and Planetary Sciences
Noble gases are very rare elements in most relevant samples in geochemistry and cosmochemistry. Noble gases may perhaps also look rather boring to chemists, as they do not form any stable compounds. However, it is just their rarity and chemical inertness which makes noble gases versatile elements in a very wide range of fields, such as oceanography, climatology, environmental sciences, meteorite studies, rock dating, early solar system and early Earth history, and many others. Mass spectrometry is by far the main analytical tool in noble gas geochemistry and cosmochemistry, partly because the rarity of noble gases often allows researchers to recognize in the same sample different noble gas "components" of different origin and hence different isotopic composition. This contribution attempts to illustrate the wide range of applications of noble gas mass spectrometry in the Earth sciences with selected examples
L-2-Amino-3-phosphonopropionsäure (AP-3): ein bedeutendes Phosphor-Analogon der L-Asparaginsäure: Chemical Education
Im Artikel werden didaktisch nützliche Informationen zu Eigenschaften, (Bio)synthese und Anwendungen der L-2-Amino-3-phosphonopropionsäure (AP-3) zusammengestellt. Das Material ist zur Ergänzung chemischer Grundlagenvorlesungen im Hochschulbereich, aber ggf. auch für spezialisiertere Unterrichtseinheiten gedacht und einsetzbar
Novel Time-of-Flight Residual Gas Analyzer (TOF-RGA) for in situ Real-time Process Monitoring
Sensitive gas analyses, in particular in industrial processes, are nowadays performed either via spectroscopy or using quadrupole mass spectrometers; the first method provides a fast but indirect measurement, whereas the second provides in situ measurements of only one species at a time. In this article, we present a novel time-of-flight residual gas analyzer (TOF-RGA) built by the Swiss company Spacetek Technology AG, and show the results of measurements such as the characterization of the FC5311 calibration compound, the detection of naturally abundant noble gases in air, the measurement of a noble gas mixture in the ultra-high vacuum facilities of CERN, and measurements acquired in a X-ray Photoelectron Spectroscopy facility in Germany, to demonstrate the capability of this new TOF-RGA to compete with already existing techniques for the monitoring of the composition of gases in real time (10 times per second), at high resolution (m/?m = 1 200 measured at m/z 132), and with a high sensitivity at ppb level
Structural Analysis of Monoclonal Antibodies with Top-down and Middle-down Electron Transfer Dissociation Mass Spectrometry: The First Decade
Monoclonal antibodies (mAbs) are protein biotherapeutics with a proven efficacy toward fighting life-threatening diseases. Their exceptional healing potential drives the annual increase in the number of novel mAbs and other antibody-like molecules entering clinical trials and the number of approved mAb-based drugs. Mass spectrometry (MS) offers high selectivity and specificity for the potentially unambiguous identification and comprehensive structural characterization of proteins, including at the proteoform level. It is thus not surprising that MS-based approaches are playing a central role in the biopharma laboratories, complementing and advancing traditional biotherapeutics characterization workflows. A combination of MS approaches is required to comprehensively characterize mAbs’ structures: the commonly employed bottom-up MS approaches are efficiently complemented with mass measurements at the intact and subunit (middle-up) levels, together with product ion analysis following gas-phase fragmentation of precursor ions performed at the intact (top-down) and subunit (middle-down) levels. Here we overview our group’s contribution to increasing the efficiency of these approaches and the development of the novel strategies over the past decade. Our particular focus has been on the top-down and middle-down MS methods that utilize electron transfer dissociation (ETD) for gas-phase protein ion fragmentation. Several approaches pioneered by our group, particularly an ETD-based middle-down approach, constitute a part of commercial software solutions for the mAb’s characterization workflows