@unpublished{8063, abstract = {We present a generative model of images that explicitly reasons over the set of objects they show. Our model learns a structured latent representation that separates objects from each other and from the background; unlike prior works, it explicitly represents the 2D position and depth of each object, as well as an embedding of its segmentation mask and appearance. The model can be trained from images alone in a purely unsupervised fashion without the need for object masks or depth information. Moreover, it always generates complete objects, even though a significant fraction of training images contain occlusions. Finally, we show that our model can infer decompositions of novel images into their constituent objects, including accurate prediction of depth ordering and segmentation of occluded parts.}, author = {Anciukevicius, Titas and Lampert, Christoph and Henderson, Paul M}, booktitle = {arXiv}, title = {{Object-centric image generation with factored depths, locations, and appearances}}, year = {2020}, } @misc{8067, abstract = {With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, lithium metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (polymeric and inorganic), Lithium-sulphur and Li-O2 (air) batteries. A particular attention is paid to review recent developments in regard of prototype manufacturing and current state-ofthe-art of these battery technologies with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7.}, author = {Varzi, Alberto and Thanner, Katharina and Scipioni, Roberto and Di Lecce, Daniele and Hassoun, Jusef and Dörfler, Susanne and Altheus, Holger and Kaskel, Stefan and Prehal, Christian and Freunberger, Stefan Alexander}, issn = {2664-1690}, keywords = {Battery, Lithium metal, Lithium-sulphur, Lithium-air, All-solid-state}, pages = {63}, publisher = {IST Austria}, title = {{Current status and future perspectives of Lithium metal batteries}}, doi = {10.15479/AT:ISTA:8067}, year = {2020}, } @article{8077, abstract = {The projection methods with vanilla inertial extrapolation step for variational inequalities have been of interest to many authors recently due to the improved convergence speed contributed by the presence of inertial extrapolation step. However, it is discovered that these projection methods with inertial steps lose the Fejér monotonicity of the iterates with respect to the solution, which is being enjoyed by their corresponding non-inertial projection methods for variational inequalities. This lack of Fejér monotonicity makes projection methods with vanilla inertial extrapolation step for variational inequalities not to converge faster than their corresponding non-inertial projection methods at times. Also, it has recently been proved that the projection methods with vanilla inertial extrapolation step may provide convergence rates that are worse than the classical projected gradient methods for strongly convex functions. In this paper, we introduce projection methods with alternated inertial extrapolation step for solving variational inequalities. We show that the sequence of iterates generated by our methods converges weakly to a solution of the variational inequality under some appropriate conditions. The Fejér monotonicity of even subsequence is recovered in these methods and linear rate of convergence is obtained. The numerical implementations of our methods compared with some other inertial projection methods show that our method is more efficient and outperforms some of these inertial projection methods.}, author = {Shehu, Yekini and Iyiola, Olaniyi S.}, issn = {0168-9274}, journal = {Applied Numerical Mathematics}, pages = {315--337}, publisher = {Elsevier}, title = {{Projection methods with alternating inertial steps for variational inequalities: Weak and linear convergence}}, doi = {10.1016/j.apnum.2020.06.009}, volume = {157}, year = {2020}, } @unpublished{8081, abstract = {Here, we employ micro- and nanosized cellulose particles, namely paper fines and cellulose nanocrystals, to induce hierarchical organization over a wide length scale. After processing them into carbonaceous materials, we demonstrate that these hierarchically organized materials outperform the best materials for supercapacitors operating with organic electrolytes reported in literature in terms of specific energy/power (Ragone plot) while showing hardly any capacity fade over 4,000 cycles. The highly porous materials feature a specific surface area as high as 2500 m2ˑg-1 and exhibit pore sizes in the range of 0.5 to 200 nm as proven by scanning electron microscopy and N2 physisorption. The carbonaceous materials have been further investigated by X-ray photoelectron spectroscopy and RAMAN spectroscopy. Since paper fines are an underutilized side stream in any paper production process, they are a cheap and highly available feedstock to prepare carbonaceous materials with outstanding performance in electrochemical applications. }, author = {Hobisch, Mathias A. and Mourad, Eléonore and Fischer, Wolfgang J. and Prehal, Christian and Eyley, Samuel and Childress, Anthony and Zankel, Armin and Mautner, Andreas and Breitenbach, Stefan and Rao, Apparao M. and Thielemans, Wim and Freunberger, Stefan Alexander and Eckhart, Rene and Bauer, Wolfgang and Spirk, Stefan }, title = {{High specific capacitance supercapacitors from hierarchically organized all-cellulose composites}}, year = {2020}, } @article{8084, abstract = {Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.}, author = {Lombardi, Fabrizio and Gómez-Extremera, Manuel and Bernaola-Galván, Pedro and Vetrivelan, Ramalingam and Saper, Clifford B. and Scammell, Thomas E. and Ivanov, Plamen Ch.}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {1}, pages = {171--190}, publisher = {Society for Neuroscience}, title = {{Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake}}, doi = {10.1523/jneurosci.1278-19.2019}, volume = {40}, year = {2020}, } @inproceedings{8089, abstract = {We consider the classical problem of invariant generation for programs with polynomial assignments and focus on synthesizing invariants that are a conjunction of strict polynomial inequalities. We present a sound and semi-complete method based on positivstellensaetze, i.e. theorems in semi-algebraic geometry that characterize positive polynomials over a semi-algebraic set. On the theoretical side, the worst-case complexity of our approach is subexponential, whereas the worst-case complexity of the previous complete method (Kapur, ACA 2004) is doubly-exponential. Even when restricted to linear invariants, the best previous complexity for complete invariant generation is exponential (Colon et al, CAV 2003). On the practical side, we reduce the invariant generation problem to quadratic programming (QCLP), which is a classical optimization problem with many industrial solvers. We demonstrate the applicability of our approach by providing experimental results on several academic benchmarks. To the best of our knowledge, the only previous invariant generation method that provides completeness guarantees for invariants consisting of polynomial inequalities is (Kapur, ACA 2004), which relies on quantifier elimination and cannot even handle toy programs such as our running example.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar and Goharshady, Ehsan Kafshdar}, booktitle = {Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation}, isbn = {9781450376136}, location = {London, United Kingdom}, pages = {672--687}, publisher = {Association for Computing Machinery}, title = {{Polynomial invariant generation for non-deterministic recursive programs}}, doi = {10.1145/3385412.3385969}, year = {2020}, } @article{8091, abstract = {In the setting of the fractional quantum Hall effect we study the effects of strong, repulsive two-body interaction potentials of short range. We prove that Haldane’s pseudo-potential operators, including their pre-factors, emerge as mathematically rigorous limits of such interactions when the range of the potential tends to zero while its strength tends to infinity. In a common approach the interaction potential is expanded in angular momentum eigenstates in the lowest Landau level, which amounts to taking the pre-factors to be the moments of the potential. Such a procedure is not appropriate for very strong interactions, however, in particular not in the case of hard spheres. We derive the formulas valid in the short-range case, which involve the scattering lengths of the interaction potential in different angular momentum channels rather than its moments. Our results hold for bosons and fermions alike and generalize previous results in [6], which apply to bosons in the lowest angular momentum channel. Our main theorem asserts the convergence in a norm-resolvent sense of the Hamiltonian on the whole Hilbert space, after appropriate energy scalings, to Hamiltonians with contact interactions in the lowest Landau level.}, author = {Seiringer, Robert and Yngvason, Jakob}, issn = {15729613}, journal = {Journal of Statistical Physics}, pages = {448--464}, publisher = {Springer}, title = {{Emergence of Haldane pseudo-potentials in systems with short-range interactions}}, doi = {10.1007/s10955-020-02586-0}, volume = {181}, year = {2020}, } @inbook{8092, abstract = {Image translation refers to the task of mapping images from a visual domain to another. Given two unpaired collections of images, we aim to learn a mapping between the corpus-level style of each collection, while preserving semantic content shared across the two domains. We introduce xgan, a dual adversarial auto-encoder, which captures a shared representation of the common domain semantic content in an unsupervised way, while jointly learning the domain-to-domain image translations in both directions. We exploit ideas from the domain adaptation literature and define a semantic consistency loss which encourages the learned embedding to preserve semantics shared across domains. We report promising qualitative results for the task of face-to-cartoon translation. The cartoon dataset we collected for this purpose, “CartoonSet”, is also publicly available as a new benchmark for semantic style transfer at https://google.github.io/cartoonset/index.html.}, author = {Royer, Amélie and Bousmalis, Konstantinos and Gouws, Stephan and Bertsch, Fred and Mosseri, Inbar and Cole, Forrester and Murphy, Kevin}, booktitle = {Domain Adaptation for Visual Understanding}, editor = {Singh, Richa and Vatsa, Mayank and Patel, Vishal M. and Ratha, Nalini}, isbn = {9783030306717}, pages = {33--49}, publisher = {Springer Nature}, title = {{XGAN: Unsupervised image-to-image translation for many-to-many mappings}}, doi = {10.1007/978-3-030-30671-7_3}, year = {2020}, } @article{8093, abstract = {Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment. Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo. Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system. Conclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.}, author = {Hippe, Andreas and Braun, Stephan Alexander and Oláh, Péter and Gerber, Peter Arne and Schorr, Anne and Seeliger, Stephan and Holtz, Stephanie and Jannasch, Katharina and Pivarcsi, Andor and Buhren, Bettina and Schrumpf, Holger and Kislat, Andreas and Bünemann, Erich and Steinhoff, Martin and Fischer, Jens and Lira, Sérgio A. and Boukamp, Petra and Hevezi, Peter and Stoecklein, Nikolas Hendrik and Hoffmann, Thomas and Alves, Frauke and Sleeman, Jonathan and Bauer, Thomas and Klufa, Jörg and Amberg, Nicole and Sibilia, Maria and Zlotnik, Albert and Müller-Homey, Anja and Homey, Bernhard}, issn = {1532-1827}, journal = {British Journal of Cancer}, pages = {942--954}, publisher = {Springer Nature}, title = {{EGFR/Ras-induced CCL20 production modulates the tumour microenvironment}}, doi = {10.1038/s41416-020-0943-2}, volume = {123}, year = {2020}, } @misc{8097, abstract = {Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by "translation bottlenecks": points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of "continuous epistasis" in bacterial physiology.}, author = {Kavcic, Bor}, keywords = {Escherichia coli, antibiotic combinations, translation, growth laws, drug interactions, bacterial physiology, translation inhibitors}, publisher = {Institute of Science and Technology Austria}, title = {{Analysis scripts and research data for the paper "Mechanisms of drug interactions between translation-inhibiting antibiotics"}}, doi = {10.15479/AT:ISTA:8097}, year = {2020}, } @article{8099, abstract = {Sewall Wright developed FST for describing population differentiation and it has since been extended to many novel applications, including the detection of homomorphic sex chromosomes. However, there has been confusion regarding the expected estimate of FST for a fixed difference between the X‐ and Y‐chromosome when comparing males and females. Here, we attempt to resolve this confusion by contrasting two common FST estimators and explain why they yield different estimates when applied to the case of sex chromosomes. We show that this difference is true for many allele frequencies, but the situation characterized by fixed differences between the X‐ and Y‐chromosome is among the most extreme. To avoid additional confusion, we recommend that all authors using FST clearly state which estimator of FST their work uses.}, author = {Gammerdinger, William J and Toups, Melissa A and Vicoso, Beatriz}, issn = {1755-0998}, journal = {Molecular Ecology Resources}, number = {6}, pages = {1517--1525}, publisher = {Wiley}, title = {{Disagreement in FST estimators: A case study from sex chromosomes}}, doi = {10.1111/1755-0998.13210}, volume = {20}, year = {2020}, } @article{8101, abstract = {By rigorously accounting for mesoscale spatial correlations in donor/acceptor surface properties, we develop a scale-spanning model for same-material tribocharging. We find that mesoscale correlations affect not only the magnitude of charge transfer but also the fluctuations—suppressing otherwise overwhelming charge-transfer variability that is not observed experimentally. We furthermore propose a generic theoretical mechanism by which the mesoscale features might emerge, which is qualitatively consistent with other proposals in the literature.}, author = {Grosjean, Galien M and Wald, Sebastian and Sobarzo Ponce, Juan Carlos A and Waitukaitis, Scott R}, issn = {2475-9953}, journal = {Physical Review Materials}, keywords = {electric charge, tribocharging, soft matter, granular materials, polymers}, number = {8}, publisher = {American Physical Society}, title = {{Quantitatively consistent scale-spanning model for same-material tribocharging}}, doi = {10.1103/PhysRevMaterials.4.082602}, volume = {4}, year = {2020}, } @article{8105, abstract = {Physical and biological systems often exhibit intermittent dynamics with bursts or avalanches (active states) characterized by power-law size and duration distributions. These emergent features are typical of systems at the critical point of continuous phase transitions, and have led to the hypothesis that such systems may self-organize at criticality, i.e. without any fine tuning of parameters. Since the introduction of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality (SOC) has been very fruitful for the analysis of emergent collective behaviors in a number of systems, including the brain. Although considerable effort has been devoted in identifying and modeling scaling features of burst and avalanche statistics, dynamical aspects related to the temporal organization of bursts remain often poorly understood or controversial. Of crucial importance to understand the mechanisms responsible for emergent behaviors is the relationship between active and quiet periods, and the nature of the correlations. Here we investigate the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity during the sleep-wake cycle. We show the duality of power-law (θ, active phase) and exponential-like (δ, quiescent phase) duration distributions, typical of SOC, jointly emerge with power-law temporal correlations and anti-correlated coupling between active and quiet states. Importantly, we demonstrate that such temporal organization shares important similarities with earthquake dynamics, and propose that specific power-law correlations and coupling between active and quiet states are distinctive characteristics of a class of systems with self-organization at criticality.}, author = {Lombardi, Fabrizio and Wang, Jilin W.J.L. and Zhang, Xiyun and Ivanov, Plamen Ch}, issn = {2100-014X}, journal = {EPJ Web of Conferences}, publisher = {EDP Sciences}, title = {{Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality}}, doi = {10.1051/epjconf/202023000005}, volume = {230}, year = {2020}, } @article{8112, author = {Barton, Nicholas H}, issn = {1471-2970}, journal = {Philosophical Transactions of the Royal Society. Series B: Biological Sciences}, number = {1806}, publisher = {The Royal Society}, title = {{On the completion of speciation}}, doi = {10.1098/rstb.2019.0530}, volume = {375}, year = {2020}, } @article{8126, abstract = {Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.}, author = {Agnes, Everton J. and Luppi, Andrea I. and Vogels, Tim P}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {50}, pages = {9634--9649}, publisher = {Society for Neuroscience}, title = {{Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields}}, doi = {10.1523/JNEUROSCI.0276-20.2020}, volume = {40}, year = {2020}, } @article{8127, abstract = {Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.}, author = {Gonçalves, Pedro J. and Lueckmann, Jan-Matthis and Deistler, Michael and Nonnenmacher, Marcel and Öcal, Kaan and Bassetto, Giacomo and Chintaluri, Chaitanya and Podlaski, William F. and Haddad, Sara A. and Vogels, Tim P and Greenberg, David S. and Macke, Jakob H.}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Training deep neural density estimators to identify mechanistic models of neural dynamics}}, doi = {10.7554/eLife.56261}, volume = {9}, year = {2020}, } @article{8130, abstract = {We study the dynamics of a system of N interacting bosons in a disc-shaped trap, which is realised by an external potential that confines the bosons in one spatial dimension to an interval of length of order ε. The interaction is non-negative and scaled in such a way that its scattering length is of order ε/N, while its range is proportional to (ε/N)β with scaling parameter β∈(0,1]. We consider the simultaneous limit (N,ε)→(∞,0) and assume that the system initially exhibits Bose–Einstein condensation. We prove that condensation is preserved by the N-body dynamics, where the time-evolved condensate wave function is the solution of a two-dimensional non-linear equation. The strength of the non-linearity depends on the scaling parameter β. For β∈(0,1), we obtain a cubic defocusing non-linear Schrödinger equation, while the choice β=1 yields a Gross–Pitaevskii equation featuring the scattering length of the interaction. In both cases, the coupling parameter depends on the confining potential.}, author = {Bossmann, Lea}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {11}, pages = {541--606}, publisher = {Springer Nature}, title = {{Derivation of the 2d Gross–Pitaevskii equation for strongly confined 3d Bosons}}, doi = {10.1007/s00205-020-01548-w}, volume = {238}, year = {2020}, } @article{8131, abstract = {The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.}, author = {Basilico, Bernadette and Morandell, Jasmin and Novarino, Gaia}, issn = {18790380}, journal = {Current Opinion in Genetics and Development}, number = {12}, pages = {126--137}, publisher = {Elsevier}, title = {{Molecular mechanisms for targeted ASD treatments}}, doi = {10.1016/j.gde.2020.06.004}, volume = {65}, year = {2020}, } @article{8132, abstract = {The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity.}, author = {Salzer, Elisabeth and Zoghi, Samaneh and Kiss, Máté G. and Kage, Frieda and Rashkova, Christina and Stahnke, Stephanie and Haimel, Matthias and Platzer, René and Caldera, Michael and Ardy, Rico Chandra and Hoeger, Birgit and Block, Jana and Medgyesi, David and Sin, Celine and Shahkarami, Sepideh and Kain, Renate and Ziaee, Vahid and Hammerl, Peter and Bock, Christoph and Menche, Jörg and Dupré, Loïc and Huppa, Johannes B. and Sixt, Michael K and Lomakin, Alexis and Rottner, Klemens and Binder, Christoph J. and Stradal, Theresia E.B. and Rezaei, Nima and Boztug, Kaan}, issn = {24709468}, journal = {Science Immunology}, number = {49}, publisher = {AAAS}, title = {{The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity}}, doi = {10.1126/sciimmunol.abc3979}, volume = {5}, year = {2020}, } @article{8133, abstract = {The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn’s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.}, author = {Hillary, Robert F. and Trejo-Banos, Daniel and Kousathanas, Athanasios and Mccartney, Daniel L. and Harris, Sarah E. and Stevenson, Anna J. and Patxot, Marion and Ojavee, Sven Erik and Zhang, Qian and Liewald, David C. and Ritchie, Craig W. and Evans, Kathryn L. and Tucker-Drob, Elliot M. and Wray, Naomi R. and Mcrae, Allan F. and Visscher, Peter M. and Deary, Ian J. and Robinson, Matthew Richard and Marioni, Riccardo E.}, issn = {1756994X}, journal = {Genome Medicine}, number = {1}, publisher = {Springer Nature}, title = {{Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults}}, doi = {10.1186/s13073-020-00754-1}, volume = {12}, year = {2020}, }