@misc{21422, author = {Sunko, Veronika}, publisher = {Institute of Science and Technology Austria}, title = {{Data underpinning "Magneto-optical Kerr effect in an A-type antiferromagnet"}}, doi = {10.15479/AT-ISTA-21422}, year = {2026}, } @article{21759, abstract = {Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype-phenotype (GP) map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the second of a two-part series, we review the application of evolutionary concepts — epistasis, robustness, evolvability, tunability, plasticity, and bet-hedging — to the evolution of gene regulatory sequences. We then evaluate the potential for a unifying theory for the evolution of regulatory sequences and identify key open challenges.}, author = {Mascolo, Elia and Körei, Reka E and Borst, Noa O. and Barton, Nicholas H and Crocker, Justin and Tkačik, Gašper}, issn = {1879-0380}, journal = {Current Opinion in Genetics and Development}, publisher = {Elsevier}, title = {{Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges}}, doi = {10.1016/j.gde.2026.102472}, volume = {98}, year = {2026}, } @article{21849, abstract = {The development of complex tissues relies on the precise assignment of cell identity. At the molecular scale, this process depends on the deposition of epigenetic modifications—such as methylation—that are regulated by complex biochemical networks and occur at specific regions on the DNA and chromatin. Here we show that despite the complexity of epigenetic regulation, dynamical scaling and self-similarity of DNA methylation marks emerge in embryonic development. Drawing on single-cell multi-omics experiments, super-resolution microscopy and statistical physics, we demonstrate that these phenomena originate in dynamical feedback between DNA methylation and the formation of nanoscale dynamic chromatin aggregates. These nanoscale processes lead to genome-wide increase in DNA methylation marks following a power law and self-similar correlation functions. Using this framework, we identify methylation patterns that precede gene expression changes in embryonic symmetry breaking. Our work identifies linear sequencing measurements as a laboratory to study mesoscopic biophysical processes in vivo.}, author = {Olmeda, Fabrizio and Lohoff, Tim and Kafetzopoulos, Ioannis and Clark, Stephen J. and Benson, Laura and Santos, Fatima and Krueger, Felix and Walker, Simon and Reik, Wolf and Rulands, Steffen}, issn = {1745-2481}, journal = {Nature Physics}, pages = {931--940}, publisher = {Springer Nature}, title = {{Scaling and self-similarity in the formation of the embryonic epigenome}}, doi = {10.1038/s41567-026-03263-x}, volume = {22}, year = {2026}, } @article{21883, abstract = {Three-dimensional (3D) printing has rapidly developed from a niche hobbyist activity into a widely accessible and indispensable technology across multiple scientific disciplines. Within microscopy, optical engineering laboratories and imaging core facilities, 3D printing enables creating customised solutions for sample holders, optical components and everyday laboratory tools that traditionally required specialised machining. By providing rapid prototyping, low-cost production and reproducibility, 3D printing facilitates innovation and efficiency in facility operations. This article provides a perspective on the possibilities, challenges, and practical aspects of implementing 3D printing within microscopy core facilities. Instead of providing technical review about 3D printing, we focus on service organisation, user engagement, resource management and community-driven repositories for design dissemination. Our aim is to share insights with those considering the implementation of 3D printing as a service for developing add-on components to ease the operation of different aspects of the machine-park driven services and those who are managing advanced instrumentation within research groups.}, author = {Goudarzi, Mohammad and Schuster, Maximilian and Milberger, Arthur and Gunkel, Manuel and Terjung, Stefan and Krens, Gabriel}, issn = {1365-2818}, journal = {Journal of Microscopy}, number = {3}, pages = {382--395}, publisher = {Wiley}, title = {{3D printing in core facilities – Low pain, high gain}}, doi = {10.1111/jmi.70106}, volume = {302}, year = {2026}, } @article{21872, abstract = {Magneto-optic Kerr effect (MOKE) is a powerful probe of broken time-reversal symmetry (T), typically used to study ferromagnets. While MOKE has been observed in some antiferromagnets (AFMs) with vanishing magnetization, it is often associated with structures whose symmetry is lower than basic collinear, bipartite order. In contrast, theory predicts a mechanism for MOKE intrinsic to all AFMs of A-type, i.e. layered AFMs in which ferromagnetic layers are antiferromagnetically aligned. Here we report the experimental confirmation of this mechanism in a bulk AFM. We achieve this by measuring the imaginary component of MOKE as a function of photon energy in MnBi2Te4, an A-type AFM where T is preserved in combination with a translation, and comparing the experimental results with model calculations. Our model suggests that observable MOKE should be expected in all collinear A-type AFMs with out-of-plane spin order, thus enabling optical detection of AFM domains and expanding the scope of MOKE to few-layer AFMs.}, author = {Sunko, Veronika and Ahsanullah, Salman and Jain, Vivek and Weber, Sophie and Kumaran, Sivaloganathan and Yan, Jiaqiang and Orenstein, Joseph and Ovchinnikov, Dmitry}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Magneto-optical Kerr effect in an A-type antiferromagnet}}, doi = {10.1038/s41467-026-72577-4}, volume = {17}, year = {2026}, } @article{21950, abstract = {One Health initiatives are modern paradigms for research and health care practices in various fields. Concrete definitions of the One Health framework, however, remain heterogeneous, leading to conceptual problems and uncertainties in the application of the framework. This article discusses several approaches to the One Health concept, and their associated consequences, with special focus on animal experimentation. The first issue addressed is how One Health should be defined, as well as what (and who) should be considered within a One Health approach. In order to shed further light on this, we explore the history of animals in biomedical science, highlighting historical milestones in the use of animal models, as well as the development and current state of ethical considerations in the field of animal experimentation. The second issue comes with the inclusion of animal experimentation per se as part of the One Health concept. Therefore, particular attention is paid to bioethical principles and the resulting problems that can arise when applying them to the One Health concept. Arguments such as the idea of inequality between humans and non-human animals, and the premise that all actions are done for the benefit of humans, are raised and then used to explore the question of whether the One Health concept is compatible with existing bioethical principles. Based on the bioethical principles of protecting the environment, the biodiversity and biosphere, this paper seeks an inclusive perspective of the One Health concept. Successful solutions will be based on this concept, which embraces all living beings. The authors conclude that a multispecies ethics approach could help create a more ethical ecosystem that is aligned with the wellbeing of all life on a shared planet.}, author = {Ulman, Yesim Isil and Kostomitsopoulos, Nikos and Camenzind, Samuel and Kitsara, Maria and Pavone, Ilja Richard and Schober, Sophie}, issn = {2632-3559}, journal = {Alternatives to Laboratory Animals}, number = {4}, pages = {226--235}, publisher = {SAGE Publications}, title = {{Emerging bioethical conflicts: One Health and animal experimentation}}, doi = {10.1177/02611929261453330}, volume = {54}, year = {2026}, } @article{21900, abstract = {Individually silencing 125 fruit fly genes reveals opposing fitness effects of mutations between females and males, as well as between germline and somatic tissues.}, author = {Ruzicka, Filip}, issn = {2397-334X}, journal = {Nature Ecology & Evolution}, pages = {1035--1036}, publisher = {Springer Nature}, title = {{Reverse genetics of sexual antagonism}}, doi = {10.1038/s41559-026-03036-y}, volume = {10}, year = {2026}, } @phdthesis{21957, abstract = {This thesis investigates algorithmic certification and approximation methods for degenerate semidefinite programs (SDPs) and the singular roots of polynomial systems. In the first part, we present a hybrid symbolic-numeric algorithm for certifying the feasibility of weakly feasible, degenerate SDPs. By reformulating linear matrix inequalities (LMIs) into a structured polynomial system via facial reduction and incidence varieties, we guarantee the existence of an isolated exact solution. This algebraic reduction enables the certification of maximum-rank numerical approximations using methods from algebraic geometry. In the second part, we address the severe ill-conditioning and loss of quadratic convergence that plague standard path-tracking methods near isolated singular roots. To overcome this, we propose tracking algorithms that achieve superlinear convergence without the computational bloat characteristic of classical deflation techniques. By modeling the solution path as a generalized fractional Puiseux series, our approach combines an explicitly derived algebraic predictor with a localized hyperplane desingularization phase during the corrector step. Furthermore, we introduce a continuous path-limit method and an extension of the geometric sequence rule to directly extract exact fractional exponents. This bypasses traditional heuristic trial-and-error methods and explicitly accommodates sparse series expansions. Numerical experiments confirm that our method significantly reduces the cumulative number of matrix inversions while achieving high-accuracy root approximations, even for heavily degenerate systems exhibiting higher coranks.}, author = {Zapata, Jeferson}, isbn = {978-3-99078-079-4}, issn = {2663-337X}, pages = {89}, publisher = {Institute of Science and Technology Austria}, title = {{Overcoming degeneracy and singularity: Techniques for semidefinite programs and homotopy continuation endgames}}, doi = {10.15479/AT-ISTA-21957}, year = {2026}, } @phdthesis{21360, author = {Riegler, Stefan}, issn = {2663-337X}, pages = {185}, publisher = {Institute of Science and Technology Austria}, title = {{Root system plasticity under nutrient limitation: Investigating hormonal and molecular drivers in Arabidopsis thaliana and Coffea species}}, doi = {10.15479/AT-ISTA-21360}, year = {2026}, } @misc{21363, abstract = {The data contains information on coffee differential gene expression as well as co-expression and trait correlations in two separate experiments. First, contrasting nitrogen supply, second, intra- and interspecific grafting.}, author = {Riegler, Stefan}, publisher = {Institute of Science and Technology Austria}, title = {{Thesis Data for Root System Plasticity under Nutrient Limitation: Investigating Hormonal and Molecular Drivers in Arabidopsis thaliana and Coffea species}}, doi = {10.15479/AT-ISTA-21363}, year = {2026}, } @phdthesis{22334, abstract = {Characterizing protein dynamics at the atomic level is essential for our understanding of biological mechanisms. Whether it is to facilitate metabolite transport, catalyze reactions, transmit signals, or regulate metabolism – proteins are constantly in motion and sample multiple conformational states to fulfill their function. Nuclear magnetic resonance (NMR) spectroscopy is particularly well suited to elucidate the dynamics of biomolecules on their complex free-energy landscape. In particular, solid-state magic-angle spinning (MAS) NMR enables the study of large molecular assemblies, protein crystals, or insoluble proteins at atomic resolution without an inherent molecular size limitation. MAS NMR experiments to probe protein dynamics are extremely versatile and sensitive to motional timescales from picoseconds to seconds. Over the past decades, technological advances, developments in experimental design, and new isotope-labeling approaches have further expanded the possibilities of this technique and significantly improved the accuracy of the determined motional parameters. Functionally important sites of proteins often contain aromatic residues. Their side-chain motions have therefore long served as valuable indicators of mechanistically relevant dynamics in NMR studies. In this thesis, site-specifically labeled aromatic residues act as sensitive reporters for MAS NMR studies of protein dynamics. The first part addresses how different environments impact side-chain motion by probing ring flips of phenylalanines and tyrosines in crystalline proteins and amyloid fibrils. It provides important insights for the analysis of dynamics obtained in non-native protein environments and emphasizes the complex factors that determine the timescale of internal dynamics. In the second part, the focus shifts towards methodological questions regarding the investigation of protein dynamics by 19F MAS NMR. The fluorine nucleus exhibits promising characteristics for NMR studies but also presents significant challenges, which is why the full methodological potential of 19F MAS NMR has not been fully realized yet. This work demonstrates that paramagnetic doping can considerably reduce the measurement time and improve the sensitivity of fluorinated samples. Finally, 19F MAS NMR is evaluated as a tool for studying protein side-chain dynamics on the example of tryptophans. The results illustrate the challenges in analyzing such experiments and lay the foundation for further development of 19F MAS NMR relaxation studies. Taken together, this thesis highlights the potential of combining specific isotope labeling, MAS NMR, and complementary methods such as crystallography and computational simulations to elucidate internal protein dynamics. The further development of such integrative approaches will be crucial to improving our understanding of complex mechanisms and protein function. }, author = {Becker, Lea Marie}, isbn = {978-3-99078-084-8}, issn = {2663-337X}, pages = {205}, publisher = {Institute of Science and Technology Austria}, title = {{Exploring protein dynamics using specific labeling approaches for solid-state MAS NMR}}, doi = {10.15479/AT-ISTA-22334}, year = {2026}, } @article{22105, abstract = {Protein conformational energy landscapes are shaped not only by intramolecular interactions but also by their environment. In protein crystals and protein–protein complexes, intermolecular contacts alter this energy landscape, but the exact nature of this alteration is difficult to decipher. Understanding how the crystal lattice affects protein dynamics is crucial for crystallography-based studies of motion, yet its influence on collective motions remains unclear. Aromatic ring flips in the hydrophobic core represent sensitive probes of such dynamics. Here, we compare the kinetics of aromatic ring flips in the protein GB1 in crystals, in complex with its binding partner IgG, and in solution, combining advanced isotope labelling with quantitative NMR methods. We show that rings in the core flip nearly a thousand times less frequently in crystals than in solution. Enhanced-sampling molecular dynamics simulations, based on a crystal structure of a GB1 variant reported in this work, reproduce these elevated barriers and reveal how the crystal restrains motions.}, author = {Becker, Lea Marie and Fu, Haohao and Tatman, Benjamin and Dreydoppel, Matthias and Kapitonova, Anna and Balazs, Daniel and Weininger, Ulrich and Engilberge, Sylvain and Chipot, Christophe and Schanda, Paul}, issn = {17554349}, journal = {Nature Chemistry}, pages = {1221--1230}, publisher = {Springer Nature}, title = {{Aromatic ring flips reveal reshaping of protein dynamics in crystals and complexes}}, doi = {10.1038/s41557-026-02155-0}, volume = {18}, year = {2026}, } @article{21164, abstract = {Global emission inventories often fail to capture the complexities of vehicular pollution in regions with unique fuel mixes, such as Brazil’s extensive biofuel use, leading to significant uncertainties in atmospheric modeling. This study presents a century-long (1960–2100) bottom-up vehicular emission inventory for Brazil, leveraging locally derived emission factors. Our estimates reveal substantial discrepancies in magnitude, timing, and speciation of non-CO2 pollutants (CO, NMHC, PM2.5) compared to leading global inventories (EDGAR, CEDS, CAMS), highlighting critical inaccuracies in widely used data sets. More critically, future projections under Shared Socioeconomic Pathways (SSPs) uncover a novel positive feedback mechanism: rising temperatures significantly enhance vehicular evaporative nonmethane hydrocarbon (NMHC) emissions. This temperature-dependent increase and subsequent NMHC oxidation to CO2 suggest an overlooked pathway that could amplify climate warming and air pollution globally, particularly after a breakpoint around 2050 (p < 0.05). While historical emissions peaked in the 1990s–2000s, nonexhaust PM becomes increasingly important. Air quality simulations using our inventory in the MUSICA model show good regional PM2.5 agreement but highlight challenges in resolving local primary pollutant peaks. This comprehensive inventory provides crucial data for Brazil and uncovers globally relevant climate–chemistry interactions, urging a re-evaluation of regional specificities in global emission assessments.}, author = {Ibarra-Espinosa, Sergio and Dias de Freitas, Edmilson and Gaubert, Benjamin and Lichtig, Pablo and Ropkins, Karl and da Silva, Iara and Martins Pereira, Guilherme and Schuch, Daniel and Nascimento, Janaina and Hoinaski, Leonardo and Martins, Leila Droprinchinski and Gavidia-Calderón, Mario and Vara-Vela, Angel and Toledo de Almeida Albuquerque, Taciana and Ynoue, Rita Yuri and Diez, Sebastian and Mera, Zamir and Casallas Garcia, Alejandro and Vallejo, Fidel and Diaz, Valeria and Pedruzzi, Rizzieri and Abrutzky, Rosana and Franco, Marco A. and Huneeus, Nicolas and Jorquera, Hector and Belalcázar-Cerón, Luis Carlos and Rojas, Néstor Y. and de Fatima Andrade, Maria and Emmons, Louisa and Brasseur, Guy}, issn = {1520-5851}, journal = {Environmental Science & Technology}, number = {6}, publisher = {American Chemical Society}, title = {{A century of vehicular emissions in Brazil: Unveiling the impacts of unique fuel mix on air quality}}, doi = {10.1021/acs.est.5c08400}, volume = {60}, year = {2026}, } @article{20971, abstract = {Mountain glaciers are among the natural systems most vulnerable to climate change. However, their interactions with the atmosphere are complex and not fully understood. These interactions can trigger rapid adjustments and climate feedbacks that either amplify or attenuate atmospheric signals, influencing both glacier response and large-scale atmospheric circulation. Observing this functional coupling in nature is challenging because the key processes occur over a wide range of spatial and temporal scales. However, recent advances in observational techniques and modeling have provided new insights into these interactions. In this review, we summarize the current state of knowledge on glacier-atmosphere interactions in high-mountain regions at different scales, and highlight recent advances in observational and numerical modeling. We also highlight important knowledge gaps and outline future research directions to improve the prediction of glacier change in a warming world.}, author = {Sauter, T. and Brock, B. W. and Collier, E. and Goger, B. and Groos, A. R. and Haualand, K. F. and Mott, R. and Nicholson, L. and Prinz, R. and Shaw, Thomas and Stiperski, I. and Georgi, A. and Haugeneder, M. and Mandal, A. and Reynolds, D. and Saigger, M. and Sicart, J. E. and Voordendag, A.}, issn = {1944-9208}, journal = {Reviews of Geophysics}, number = {1}, publisher = {Wiley}, title = {{Glacier-atmosphere interactions and feedbacks in high-mountain regions - A review}}, doi = {10.1029/2024RG000869}, volume = {64}, year = {2026}, } @misc{21145, abstract = {Protein conformational energy landscapes are shaped not only by intramolecular interactions but also by their environment. In protein crystals and protein-protein complexes, intermolecular contacts alter this energy landscape, but the exact nature of this alteration is difficult to decipher. Understanding how the crystal lattice affects protein dynamics is crucial for crystallography-based studies of motion, yet its influence on collective motions remains unclear. Aromatic ring flips in the hydrophobic core represent sensitive probes of such dynamics. Here, we compare the kinetics of aromatic ring flips in the protein GB1 in crystals, in complex with its binding partner IgG, and in solution, combining advanced isotope labeling with quantitative NMR methods. We show that rings in the core flip nearly a thousand times less frequently in crystals than in solution. Enhanced-sampling molecular dynamics simulations, based on a new crystal structure, reproduce these elevated barriers and reveal how the crystal restrains motions. }, author = {Becker, Lea Marie and Schanda, Paul and Chipot, Christophe}, publisher = {Institute of Science and Technology Austria}, title = {{Additional Data for "Aromatic Ring Flips Reveal Reshaping of Protein Dynamics in Crystals and Complexes"}}, doi = {10.15479/AT-ISTA-21145}, year = {2026}, } @article{20935, abstract = {In situ cryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate the structures of biomolecules in their native context. However, challenges remain for the efficient production and sharing of large-scale cryo-ET datasets. Here, we combined cryogenic plasma-based focused ion beam (cryo-PFIB) milling with recent advances in cryo-ET acquisition and processing to generate a dataset of 1,829 annotated tomograms of the green alga Chlamydomonas reinhardtii, which we provide as a community resource to drive method development and inspire biological discovery. To assay data quality, we performed subtomogram averaging of both soluble and membrane-bound complexes ranging in size from >3 MDa to ∼200 kDa, including 80S ribosomes, Rubisco, nucleosomes, microtubules, clathrin, photosystem II, and mitochondrial ATP synthase. The majority of these density maps reached sub-nanometer resolution, demonstrating the potential of this C. reinhardtii dataset as well as the promise of modern cryo-ET workflows and open data sharing to empower visual proteomics.}, author = {Kelley, Ron and Khavnekar, Sagar and Righetto, Ricardo D. and Heebner, Jessica and Obr, Martin and Zhang, Xianjun and Chakraborty, Saikat and Tagiltsev, Grigory and Michael, Alicia and Van Dorst, Sofie and Waltz, Florent and Mccafferty, Caitlyn L. and Lamm, Lorenz and Zufferey, Simon and Van Der Stappen, Philippe and Van Den Hoek, Hugo and Wietrzynski, Wojciech and Harar, Pavol and Wan, William and Briggs, John A.G. and Plitzko, Jürgen M. and Engel, Benjamin D. and Kotecha, Abhay}, issn = {1097-4164}, journal = {Molecular Cell}, number = {1}, pages = {213--230.e7}, publisher = {Elsevier}, title = {{Toward community-driven visual proteomics with large-scale cryo-electron tomography of Chlamydomonas reinhardtii}}, doi = {10.1016/j.molcel.2025.11.029}, volume = {86}, year = {2026}, } @article{20858, abstract = {Targeted antigen delivery to immune cells, particularly dendritic cells, has emerged as a promising strategy to enhance therapeutic efficacy of vaccines, while minimizing adverse effects associated with conventional immunization. In this study, we use our previously described small glycomimetic molecule that is selectively recognized by the Langerhans cell (LC)-specific surface receptor Langerin and demonstrate specific delivery of protein antigens to these specialized dendritic cells. Our results show that Langerin-mediated antigen delivery significantly enhances the immune response in vivo, resulting in increased expansion and activation of antigen-specific T cells, compared to immunization with unmodified antigen. We demonstrate the feasibility of our LC-targeted platform for immune cell-specific immunization with protein antigen and underscore the potential of LCs as an access point for next-generation vaccines and immunotherapies.}, author = {Rica, Ramona and Klein, Klara and Johnson, Litty and Carta, Gabriele and Sarcevic, Mirza and Langer, Freyja and Rademacher, Christoph and Wawrzinek, Robert and Quattrone, Federica and Sparber, Florian}, issn = {1525-0024}, journal = {Molecular Therapy}, number = {1}, pages = {397--406}, publisher = {Elsevier}, title = {{Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response}}, doi = {10.1016/j.ymthe.2025.10.008}, volume = {34}, year = {2026}, } @article{20537, abstract = {In this personal account, I describe the work performed in my research group on the development of methods that harness heterogeneous photocatalysts for light-mediated nickel-catalyzed cross-couplings. This includes catalytic systems using carbon nitride materials, dye-sensitized TiO₂, covalent organic frameworks (COFs), and conjugated polymers. The rationale behind the selection of materials and how their use led to the identification of catalyst deactivation, structure–activity relationships, and future opportunities is discussed.}, author = {Pieber, Bartholomäus}, issn = {1437-2096}, journal = {Synlett}, number = {1}, pages = {43--54}, publisher = {Georg Thieme Verlag}, title = {{Photochemical cross-couplings using semiconducting materials}}, doi = {10.1055/a-2690-9269}, volume = {37}, year = {2026}, } @article{21987, abstract = {We introduce JODIE, a genetic joint modeling approach that estimates how DNA loci influence human traits by partitioning genetic effects into four components: direct effects (from a child’s alleles), indirect maternal and paternal effects (from parents’ alleles), and parent-of-origin (PofO) effects (dependent on parental transmission of alleles), while uniquely accounting for assortative mating. We analyze 30,000 child-mother-father trios from the Estonian Biobank and the Norwegian Mother, Father, and Child Cohort, focusing on height, body mass index, and childhood educational test scores. We find direct effects to be the largest contributor to trait variation, but combined, indirect parental and PofO effects are similarly substantial. We support our results by within-family genome-wide association testing and identify 276 independently associated DNA regions with a complex interplay between direct, indirect, and PofO effects. By joint modeling, we show that direct, indirect, and PofO effects collectively shape human phenotypic variation across loci genome-wide.}, author = {Krätschmer, Ilse and Hegemann, Laura and Hofmeister, Robin J. and Corfield, Elizabeth C. and Mahmoudi, Mahdi and Delaneau, Olivier and Andreassen, Ole A. and Campbell, Archie and Hayward, Caroline and Marioni, Riccardo E. and Ystrom, Eivind and Havdahl, Alexandra and Robinson, Matthew Richard}, issn = {2666-979X}, journal = {Cell Genomics}, keywords = {direct genetic effects, DGE, indirect genetic effects, IGE, parent-of-origin effects, phenotypic variation, assortative mating, within-family GWAS, MoBa, EstBB}, number = {7}, publisher = {Elsevier}, title = {{Separating direct, indirect, and parent-of-origin genetic effects in the human population}}, doi = {10.1016/j.xgen.2026.101277}, volume = {6}, year = {2026}, } @phdthesis{22258, abstract = {Uncovering the genetic architecture of complex traits and pinpointing causal molecular drivers require the ability to distinguish true signals from noise within massive, high-dimensional omics datasets. To extract meaningful biological insights from these datasets, such as identifying causal genetic variants and proteins, scalable and accurate inference methods are essential. To this end, this thesis develops novel Bayesian inference frameworks based on Vector Approximate Message Passing and demonstrates their effectiveness in the modeling of disease onset times and quantitative physical and clinical measures. First, we introduce gVAMP, a Bayesian framework tailored for Genome-Wide Association Studies that enables the joint modeling of quantitative complex traits across millions of genetic variants. gVAMP demonstrates superior accuracy in variable selection and out-of-sample polygenic risk prediction compared to state-of-the-art approaches. We model human height using 17 million whole-genome sequence variants from the UK Biobank, incorporating a vast number of rare variants and revealing novel associations. gVAMP achieves a prediction accuracy of approximately 46% for human height, representing the highest reported performance for this trait to date. Second, we present vampW, a Bayesian framework for survival analysis applied to proteomic data. By effectively handling right-censoring and complex protein dependencies within the UK Biobank Pharma Proteomics Project dataset, vampW identifies 219 protein associations across 24 disease outcomes, the majority of which are not among the top marginal discoveries. We further adjust protein levels for exponential age effects, yielding 1,308 associations and highlighting the sensitivity of the analysis to the chosen age-correction methodology. Finally, vampW improves upon the variable selection capabilities of the commonly used (penalized) variants of the Cox proportional hazards model and delivers state-of-the-art out-of-sample prediction of disease onset times. Collectively, these methods provide powerful tools for dissecting the genetic architecture of complex traits and the proteomic drivers of disease onset. Furthermore, by delivering accurate polygenic risk scores and precise predictions of onset times, this work advances the capabilities of personalized medicine and clinical risk stratification.}, author = {Depope, Al}, issn = {2663-337X}, keywords = {Approximate Message Passing, GWAS, Genomics, Proteomics, Survival modeling}, pages = {169}, publisher = {Institute of Science and Technology Austria}, title = {{From sparse selection to risk prediction: Approximate message passing for proteomic survival models and large-scale genomics}}, doi = {10.15479/AT-ISTA-22258}, year = {2026}, }