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1,439 results on '"Sulem P"'

1. A Hamiltonian Dysthe equation for hydroelastic waves in a compressed ice sheet

Author

Guyenne, Philippe, Kairzhan, Adilbek, and Sulem, Catherine

Subjects
Mathematics - Analysis of PDEs, Mathematical Physics, Physics - Fluid Dynamics
Abstract

Nonlinear hydroelastic waves along a compressed ice sheet lying on top of a two-dimensional fluid of infinite depth are investigated. Based on a Hamiltonian formulation of this problem and by applying techniques from Hamiltonian perturbation theory, a Hamiltonian Dysthe equation is derived for the slowly varying envelope of modulated wavetrains. This derivation is further complicated here by the presence of cubic resonances for which a detailed analysis is given. A Birkhoff normal form transformation is introduced to eliminate non-resonant triads while accommodating resonant ones. It also provides a non-perturbative scheme to reconstruct the ice-sheet deformation from the wave envelope. Linear predictions on the modulational instability of Stokes waves in sea ice are established, and implications for the existence of solitary wavepackets are discussed for a range of values of ice compression relative to ice bending. This Dysthe equation is solved numerically to test these predictions. Its numerical solutions are compared to direct simulations of the full Euler system, and very good agreement is observed., Comment: 38 pages, 11 figures

Published
2024

2. Interaction between long internal waves and free surface waves in deep water

Author

Kairzhan, Adilbek, Kennedy, Christopher, and Sulem, Catherine

Subjects
Mathematics - Analysis of PDEs
Abstract

We consider a density-stratified fluid composed of two immiscible layers separated by a sharp interface. We study the regime of long internal waves interacting with modulated surface wave packets and describe their resonant interaction by a system of equations where the internal wave solves a high-order Benjamin-Ono (BO) equation coupled to a linear Schr\"{o}dinger equation for the envelope of the free surface. The perturbation methods are based on the Hamiltonian formulation for the original system of irrotational Euler's equations as described in Benjamin-Bridges [J. Fluid Mech. 333, 1997] and Craig-Guyenne-Kalisch [Comm. Pure Appl. Math. 58, 2005]. We also establish a local wellposedness result for a reduced BO-Schr\"{o}dinger system using an approach developed by Linares-Ponce-Pilod [J. Diff. Eqs. 250, 2011]., Comment: 31 pages

Published
2024
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3. Impact of pressure anisotropy on the cascade rate of Hall-MHD turbulence with biadiabatic ions

Author

Simon, Pauline A., Sahraoui, Fouad, Galtier, Sébastien, Laveder, Dimitri, Passot, Thierry, and Sulem, Pierre-Louis

Subjects
Physics - Plasma Physics, Nonlinear Sciences - Chaotic Dynamics
Abstract

The impact of ion pressure anisotropy on the energy cascade rate of Hall-MHD turbulence with biadiabatic ions and isothermal electrons is evaluated in three-dimensional direct numerical simulations, using the exact (or third-order) law derived in \citet{simon_exact_2022}. It is shown that pressure anisotropy can enhance or reduce the cascade rate, depending on the scales, in comparison with the prediction of the exact law with isotropic pressure, by an amount that correlates well with pressure anisotropy $a_p=\frac{p_\perp}{p_\parallel}\neq1$ that develops in simulations initialized with an isotropic pressure (${a_p}_0=1$). A simulation with initial pressure anisotropy, ${a_p}_0=4$, confirms this trend, exhibiting a stronger impact on the cascade rate, both in the inertial range and at larger scales, close to the forcing scales. Furthermore, a Fourier-based numerical method, to compute exact laws in numerical simulations in the full $(\ell_\perp,\ell_\parallel)$ increment plane, is presented., Comment: 20 pages, 11 figures, submitted to PRE

Published
2024

4. Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes

Author

Smal, Noor, Majdoub, Fatma, Janssens, Katrien, Reyniers, Edwin, Meuwissen, Marije E. C., Ceulemans, Berten, Northrup, Hope, Hill, Jeremy B., Liu, Lingying, Errichiello, Edoardo, Gana, Simone, Strong, Alanna, Rohena, Luis, Franciskovich, Rachel, Murali, Chaya N., Huybrechs, An, Sulem, Telma, Fridriksdottir, Run, Sulem, Patrick, Stefansson, Kari, Bai, Yan, Rosenfeld, Jill A., Lalani, Seema R., Streff, Haley, Kooy, R. Frank, and Weckhuysen, Sarah

Published
2024
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5. Estimating the history of a random recursive tree

Author

Briend, Simon, Giraud, Christophe, Lugosi, Gábor, and Sulem, Déborah

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning, Computer Science - Social and Information Networks
Abstract

This paper studies the problem of estimating the order of arrival of the vertices in a random recursive tree. Specifically, we study two fundamental models: the uniform attachment model and the linear preferential attachment model. We propose an order estimator based on the Jordan centrality measure and define a family of risk measures to quantify the quality of the ordering procedure. Moreover, we establish a minimax lower bound for this problem, and prove that the proposed estimator is nearly optimal. Finally, we numerically demonstrate that the proposed estimator outperforms degree-based and spectral ordering procedures.

Published
2024

6. Gene-based burden tests of rare germline variants identify six cancer susceptibility genes

Author

Ivarsdottir, Erna V., Gudmundsson, Julius, Tragante, Vinicius, Sveinbjornsson, Gardar, Kristmundsdottir, Snaedis, Stacey, Simon N., Halldorsson, Gisli H., Magnusson, Magnus I., Oddsson, Asmundur, Walters, G. Bragi, Sigurdsson, Asgeir, Saevarsdottir, Saedis, Beyter, Doruk, Thorleifsson, Gudmar, Halldorsson, Bjarni V., Melsted, Pall, Stefansson, Hreinn, Jonsdottir, Ingileif, Sørensen, Erik, Pedersen, Ole B., Erikstrup, Christian, Bøgsted, Martin, Pøhl, Mette, Røder, Andreas, Stroomberg, Hein Vincent, Gögenur, Ismail, Hillingsø, Jens, Bojesen, Stig E., Lassen, Ulrik, Høgdall, Estrid, Ullum, Henrik, Brunak, Søren, Ostrowski, Sisse R., Sonderby, Ida Elken, Frei, Oleksandr, Djurovic, Srdjan, Havdahl, Alexandra, Moller, Pal, Dominguez-Valentin, Mev, Haavik, Jan, Andreassen, Ole A., Hovig, Eivind, Agnarsson, Bjarni A., Hilmarsson, Rafn, Johannsson, Oskar Th., Valdimarsson, Trausti, Jonsson, Steinn, Moller, Pall H., Olafsson, Jon H., Sigurgeirsson, Bardur, Jonasson, Jon G., Tryggvason, Geir, Holm, Hilma, Sulem, Patrick, Rafnar, Thorunn, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2024
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7. Genetic links between ovarian ageing, cancer risk and de novo mutation rates

Author

Stankovic, Stasa, Shekari, Saleh, Huang, Qin Qin, Gardner, Eugene J., Ivarsdottir, Erna V., Owens, Nick D. L., Mavaddat, Nasim, Azad, Ajuna, Hawkes, Gareth, Kentistou, Katherine A., Beaumont, Robin N., Day, Felix R., Zhao, Yajie, Jonsson, Hakon, Rafnar, Thorunn, Tragante, Vinicius, Sveinbjornsson, Gardar, Oddsson, Asmundur, Styrkarsdottir, Unnur, Gudmundsson, Julius, Stacey, Simon N., Gudbjartsson, Daniel F., Kennedy, Kitale, Wood, Andrew R., Weedon, Michael N., Ong, Ken K., Wright, Caroline F., Hoffmann, Eva R., Sulem, Patrick, Hurles, Matthew E., Ruth, Katherine S., Martin, Hilary C., Stefansson, Kari, Perry, John R. B., and Murray, Anna

Published
2024
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8. Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency

Author

Oddsson, Asmundur, Steinthorsdottir, Valgerdur, Oskarsson, Gudjon R., Styrkarsdottir, Unnur, Moore, Kristjan H. S., Isberg, Salvor, Halldorsson, Gisli H., Sveinbjornsson, Gardar, Westergaard, David, Nielsen, Henriette Svarre, Fridriksdottir, Run, Jensson, Brynjar O., Arnadottir, Gudny A., Jonsson, Hakon, Sturluson, Arni, Snaebjarnarson, Audunn S., Andreassen, Ole A., Walters, G. Bragi, Nyegaard, Mette, Erikstrup, Christian, Steingrimsdottir, Thora, Lie, Rolv T., Melsted, Pall, Jonsdottir, Ingileif, Halldorsson, Bjarni V., Thorleifsson, Gudmar, Saemundsdottir, Jona, Magnusson, Olafur Th., Banasik, Karina, Sorensen, Erik, Masson, Gisli, Pedersen, Ole Birger, Tryggvadottir, Laufey, Haavik, Jan, Ostrowski, Sisse Rye, Stefansson, Hreinn, Holm, Hilma, Rafnar, Thorunn, Gudbjartsson, Daniel F., Sulem, Patrick, and Stefansson, Kari

Published
2024
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10. Bloch-Floquet band gaps for water waves over a periodic bottom

Author

Lacave, Christophe, Ménard, Matthieu, and Sulem, Catherine

Subjects
Mathematics - Analysis of PDEs, Mathematics - Spectral Theory
Abstract

A central object in the analysis of the water wave problem is the Dirichlet-Neumann operator. This paper is devoted to the study of its spectrum in the context of the water wave system linearized near equilibrium in a domain with a variable bottom, assumed to be a $C^2$ periodic function. We use the analyticity of the Dirichlet-Neumann operator with respect to the bottom variation and combine it with general properties of elliptic systems and spectral theory for self-adjoint operators to develop a Bloch-Floquet theory and describe the structure of its spectrum. We find that under some conditions on the bottom variations, the spectrum is composed of bands separated by gaps, with explicit formulas for their sizes and locations.

Published
2024

11. Character Recognition in Byzantine Seals with Deep Neural Networks

Author

Rageau, Théophile, Likforman-Sulem, Laurence, Fiandrotti, Attilio, Eyharabide, Victoria, Caseau, Béatrice, and Cheynet, Jean-Claude

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Seals are small coin-shaped artifacts, mostly made of lead, held with strings to seal letters. This work presents the first attempt towards automatic reading of text on Byzantine seal images.Byzantine seals are generally decorated with iconography on the obverse side and Greek text on the reverse side. Text may include the sender's name, position in the Byzantine aristocracy, and elements of prayers. Both text and iconography are precious literary sources that wait to be exploited electronically, so the development of computerized systems for interpreting seals images is of paramount importance. This work's contribution is hence a deep, two-stages, character reading pipeline for transcribing Byzantine seal images. A first deep convolutional neural network (CNN) detects characters in the seal (character localization). A second convolutional network reads the localized characters (character classification). Finally, a diplomatic transcription of the seal is provided by post-processing the two network outputs. We provide an experimental evaluation of each CNN in isolation and both CNNs in combination. All performances are evaluated by cross-validation. Character localization achieves a mean average precision (mAP@0.5) greater than 0.9. Classification of characters cropped from ground truth bounding boxes achieves Top-1 accuracy greater than 0.92. End-to-end evaluation shows the efficiency of the proposed approach when compared to the SoTA for similar tasks.

Published
2024

12. Gyrofluid simulations of turbulence and reconnection in space plasmas

Author

Passot, T., Cerri, S. S., Granier, C., Laveder, D., Sulem, P. L., and Tassi, E.

Subjects
Physics - Plasma Physics, Physics - Space Physics
Abstract

A Hamiltonian two-field gyrofluid model is used to investigate the dynamics of an electron-ion collisionless plasma subject to a strong ambient magnetic field, within a spectral range extending from the magnetohydrodynamic (MHD) scales to the electron skin depth. This model isolates Alfv\'en, Kinetic Alfv\'en and Inertial Kinetic Alfv\'en waves that play a central role in space plasmas, and extends standard reduced fluid models to broader ranges of the plasma parameters. Recent numerical results are reviewed, including (i) the reconnection-mediated MHD turbulence developing from the collision of counter-propagating Alfv\'en wave packets, (ii) the specific features of the cascade dynamics in strongly imbalanced turbulence, including a possible link between the existence of a spectral transition range and the presence of co-propagating wave interactions at sub-ion scales, for which new simulations are reported, (iii) the influence of the ion-to-electron temperature ratio in two-dimensional collisionless magnetic reconnection. The role of electron finite Larmor radius corrections is pointed out and the extension of the present model to a four-field gyrofluid model is discussed. Such an extended model accurately describes electron finite Larmor radius effects at small or moderate values of the electron beta parameter, and also retains the coupling to slow magnetosonic waves., Comment: 11 figures, 52 pages

Published
2024
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13. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

Author

Ghouse, Jonas, Sveinbjörnsson, Gardar, Vujkovic, Marijana, Seidelin, Anne-Sofie, Gellert-Kristensen, Helene, Ahlberg, Gustav, Tragante, Vinicius, Rand, Søren, Brancale, Joseph, Vilarinho, Silvia, Lundegaard, Pia, Sørensen, Erik, Erikstrup, Christian, Bruun, Mie, Jensen, Bitten, Brunak, Søren, Banasik, Karina, Ullum, Henrik, Verweij, Niek, Lotta, Luca, Baras, Aris, Mirshahi, Tooraj, Carey, David, Kaplan, David, Lynch, Julie, Morgan, Timothy, Schwantes-An, Tae-Hwi, Dochtermann, Daniel, Pyarajan, Saiju, Tsao, Philip, Laisk, Triin, Mägi, Reedik, Kozlitina, Julia, Tybjærg-Hansen, Anne, Jones, David, Knowlton, Kirk, Nadauld, Lincoln, Ferkingstad, Egil, Björnsson, Einar, Ulfarsson, Magnus, Sturluson, Árni, Sulem, Patrick, Pedersen, Ole, Ostrowski, Sisse, Gudbjartsson, Daniel, Stefansson, Kari, Olesen, Morten, Chang, Kyong-Mi, Holm, Hilma, Bundgaard, Henning, and Stender, Stefan

Subjects
Humans, Liver Cirrhosis, Genome-Wide Association Study, Genetic Predisposition to Disease, Liver Neoplasms, Carcinoma, Hepatocellular, Alanine Transaminase, Polymorphism, Single Nucleotide, Male, Lipase, Female, gamma-Glutamyltransferase, Membrane Proteins, Cohort Studies, Case-Control Studies, Multifactorial Inheritance, Risk Factors, Genetic Variation
Abstract

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.

Published
2024

14. The correlation between CpG methylation and gene expression is driven by sequence variants

Author

Stefansson, Olafur Andri, Sigurpalsdottir, Brynja Dogg, Rognvaldsson, Solvi, Halldorsson, Gisli Hreinn, Juliusson, Kristinn, Sveinbjornsson, Gardar, Gunnarsson, Bjarni, Beyter, Doruk, Jonsson, Hakon, Gudjonsson, Sigurjon Axel, Olafsdottir, Thorunn Asta, Saevarsdottir, Saedis, Magnusson, Magnus Karl, Lund, Sigrun Helga, Tragante, Vinicius, Oddsson, Asmundur, Hardarson, Marteinn Thor, Eggertsson, Hannes Petur, Gudmundsson, Reynir L., Sverrisson, Sverrir, Frigge, Michael L., Zink, Florian, Holm, Hilma, Stefansson, Hreinn, Rafnar, Thorunn, Jonsdottir, Ingileif, Sulem, Patrick, Helgason, Agnar, Gudbjartsson, Daniel F., Halldorsson, Bjarni V., Thorsteinsdottir, Unnur, and Stefansson, Kari

Published
2024
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15. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.

Published
2024
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16. Influence of ion-to-electron temperature ratio on tearing instability and resulting subion-scale turbulence in a low-$\beta_e$ collisionless plasma

Author

Granier, C., Tassi, E., Laveder, D., Passot, T., and Sulem, P. L.

Subjects
Physics - Plasma Physics
Abstract

A two-field gyrofluid model including ion finite Larmor radius (FLR) corrections, magnetic fluctuations along the ambient field and electron inertia is used to study two-dimensional reconnection in a low $\beta_e$ collisionless plasma, in a plane perpendicular to the ambient field. Both moderate and large values of the ion-to-electron temperature ratio $\tau$ are considered. The linear growth rate of the tearing instability is computed for various values of $\tau$, confirming the convergence to reduced electron magnetodynamics (REMHD) predictions in the large $\tau$ limit. Comparisons with analytical estimates in several limit cases are also presented. The nonlinear dynamics leads to a fully-developed turbulent regime that appears to be sensitive to the value of the parameter $\tau$. For $\tau = 100$, strong large-scale velocity shears trigger Kelvin-Helmholtz instability, leading to the propagation of the turbulence through the separatrices, together with the formation of eddies of size of the order of the electron skin depth. In the $\tau = 1$ regime, the vortices are significantly smaller and their accurate description requires that electron FLR effects be taken into account.

Published
2023
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17. An Empirical Study of Self-supervised Learning with Wasserstein Distance

Author

Yamada, Makoto, Takezawa, Yuki, Houry, Guillaume, Dusterwald, Kira Michaela, Sulem, Deborah, Zhao, Han, and Tsai, Yao-Hung Hubert

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

In this study, we delve into the problem of self-supervised learning (SSL) utilizing the 1-Wasserstein distance on a tree structure (a.k.a., Tree-Wasserstein distance (TWD)), where TWD is defined as the L1 distance between two tree-embedded vectors. In SSL methods, the cosine similarity is often utilized as an objective function; however, it has not been well studied when utilizing the Wasserstein distance. Training the Wasserstein distance is numerically challenging. Thus, this study empirically investigates a strategy for optimizing the SSL with the Wasserstein distance and finds a stable training procedure. More specifically, we evaluate the combination of two types of TWD (total variation and ClusterTree) and several probability models, including the softmax function, the ArcFace probability model, and simplicial embedding. We propose a simple yet effective Jeffrey divergence-based regularization method to stabilize optimization. Through empirical experiments on STL10, CIFAR10, CIFAR100, and SVHN, we find that a simple combination of the softmax function and TWD can obtain significantly lower results than the standard SimCLR. Moreover, a simple combination of TWD and SimSiam fails to train the model. We find that the model performance depends on the combination of TWD and probability model, and that the Jeffrey divergence regularization helps in model training. Finally, we show that the appropriate combination of the TWD and probability model outperforms cosine similarity-based representation learning.

Published
2023

18. Sequence variants associated with BMI affect disease risk through BMI itself

Author

Gudmundur Einarsson, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Florian Zink, Hannes Helgason, Thorhildur Olafsdottir, Solvi Rognvaldsson, Vinicius Tragante, Magnus O. Ulfarsson, Gardar Sveinbjornsson, Audunn S. Snaebjarnarson, Hafsteinn Einarsson, Hildur M. Aegisdottir, Gudrun A. Jonsdottir, Anna Helgadottir, Solveig Gretarsdottir, Unnur Styrkarsdottir, Hannes K. Arnason, Ragnar Bjarnason, Emil Sigurdsson, David O. Arnar, Einar S. Bjornsson, Runolfur Palsson, Gyda Bjornsdottir, Hreinn Stefansson, Thorgeir Thorgeirsson, Patrick Sulem, Unnur Thorsteinsdottir, Hilma Holm, Daniel F. Gudbjartsson, and Kari Stefansson

Subjects
Science
Abstract

Abstract Mendelian Randomization studies indicate that BMI contributes to various diseases, but it’s unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk.

Published
2024
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19. Sequence variants influencing the regulation of serum IgG subclass levels

Author

Thorunn A. Olafsdottir, Gudmar Thorleifsson, Aitzkoa Lopez de Lapuente Portilla, Stefan Jonsson, Lilja Stefansdottir, Abhishek Niroula, Aslaug Jonasdottir, Hannes P. Eggertsson, Gisli H. Halldorsson, Gudny E. Thorlacius, Asgeir O. Arnthorsson, Unnur S. Bjornsdottir, Folkert W. Asselbergs, Arthur E. H. Bentlage, Gudmundur I. Eyjolfsson, Steinunn Gudmundsdottir, Kristbjorg Gunnarsdottir, Bjarni V. Halldorsson, Hilma Holm, Bjorn R. Ludviksson, Pall Melsted, Gudmundur L. Norddahl, Isleifur Olafsson, Saedis Saevarsdottir, Olof Sigurdardottir, Asgeir Sigurdsson, Robin Temming, Pall T. Önundarson, Unnur Thorsteinsdottir, Gestur Vidarsson, Patrick Sulem, Daniel F. Gudbjartsson, Ingileif Jonsdottir, Björn Nilsson, and Kari Stefansson

Subjects
Science
Abstract

Abstract Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.

Published
2024
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20. Sequence variants associated with BMI affect disease risk through BMI itself

Author

Einarsson, Gudmundur, Thorleifsson, Gudmar, Steinthorsdottir, Valgerdur, Zink, Florian, Helgason, Hannes, Olafsdottir, Thorhildur, Rognvaldsson, Solvi, Tragante, Vinicius, Ulfarsson, Magnus O., Sveinbjornsson, Gardar, Snaebjarnarson, Audunn S., Einarsson, Hafsteinn, Aegisdottir, Hildur M., Jonsdottir, Gudrun A., Helgadottir, Anna, Gretarsdottir, Solveig, Styrkarsdottir, Unnur, Arnason, Hannes K., Bjarnason, Ragnar, Sigurdsson, Emil, Arnar, David O., Bjornsson, Einar S., Palsson, Runolfur, Bjornsdottir, Gyda, Stefansson, Hreinn, Thorgeirsson, Thorgeir, Sulem, Patrick, Thorsteinsdottir, Unnur, Holm, Hilma, Gudbjartsson, Daniel F., and Stefansson, Kari

Published
2024
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21. Sequence variants influencing the regulation of serum IgG subclass levels

Author

Olafsdottir, Thorunn A., Thorleifsson, Gudmar, Lopez de Lapuente Portilla, Aitzkoa, Jonsson, Stefan, Stefansdottir, Lilja, Niroula, Abhishek, Jonasdottir, Aslaug, Eggertsson, Hannes P., Halldorsson, Gisli H., Thorlacius, Gudny E., Arnthorsson, Asgeir O., Bjornsdottir, Unnur S., Asselbergs, Folkert W., Bentlage, Arthur E. H., Eyjolfsson, Gudmundur I., Gudmundsdottir, Steinunn, Gunnarsdottir, Kristbjorg, Halldorsson, Bjarni V., Holm, Hilma, Ludviksson, Bjorn R., Melsted, Pall, Norddahl, Gudmundur L., Olafsson, Isleifur, Saevarsdottir, Saedis, Sigurdardottir, Olof, Sigurdsson, Asgeir, Temming, Robin, Önundarson, Pall T., Thorsteinsdottir, Unnur, Vidarsson, Gestur, Sulem, Patrick, Gudbjartsson, Daniel F., Jonsdottir, Ingileif, Nilsson, Björn, and Stefansson, Kari

Published
2024
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22. Loss-of-function variants in ITSN1 confer high risk of Parkinson’s disease

Author

Skuladottir, Astros Th., Tragante, Vinicius, Sveinbjornsson, Gardar, Helgason, Hannes, Sturluson, Arni, Bjornsdottir, Anna, Jonsson, Palmi, Palmadottir, Vala, Sveinsson, Olafur A., Jensson, Brynjar O., Gudjonsson, Sigurjon A., Ivarsdottir, Erna V., Gisladottir, Rosa S., Gunnarsson, Arni F., Walters, G. Bragi, Jonsdottir, Gudrun A., Thorgeirsson, Thorgeir E., Bjornsdottir, Gyda, Holm, Hilma, Gudbjartsson, Daniel F., Sulem, Patrick, Stefansson, Hreinn, and Stefansson, Kari

Published
2024
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23. Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Author

Went, Molly, Duran-Lozano, Laura, Halldorsson, Gisli H., Gunnell, Andrea, Ugidos-Damboriena, Nerea, Law, Philip, Ekdahl, Ludvig, Sud, Amit, Thorleifsson, Gudmar, Thodberg, Malte, Olafsdottir, Thorunn, Lamarca-Arrizabalaga, Antton, Cafaro, Caterina, Niroula, Abhishek, Ajore, Ram, Lopez de Lapuente Portilla, Aitzkoa, Ali, Zain, Pertesi, Maroulio, Goldschmidt, Hartmut, Stefansdottir, Lilja, Kristinsson, Sigurdur Y., Stacey, Simon N., Love, Thorvardur J., Rognvaldsson, Saemundur, Hajek, Roman, Vodicka, Pavel, Pettersson-Kymmer, Ulrika, Späth, Florentin, Schinke, Carolina, Van Rhee, Frits, Sulem, Patrick, Ferkingstad, Egil, Hjorleifsson Eldjarn, Grimur, Mellqvist, Ulf-Henrik, Jonsdottir, Ingileif, Morgan, Gareth, Sonneveld, Pieter, Waage, Anders, Weinhold, Niels, Thomsen, Hauke, Försti, Asta, Hansson, Markus, Juul-Vangsted, Annette, Thorsteinsdottir, Unnur, Hemminki, Kari, Kaiser, Martin, Rafnar, Thorunn, Stefansson, Kari, Houlston, Richard, and Nilsson, Björn

Published
2024
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24. Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease

Author

Saevarsdottir, Saedis, Bjarnadottir, Kristbjörg, Markusson, Thorsteinn, Berglund, Jonas, Olafsdottir, Thorunn A., Halldorsson, Gisli H., Rutsdottir, Gudrun, Gunnarsdottir, Kristbjorg, Arnthorsson, Asgeir Orn, Lund, Sigrun H., Stefansdottir, Lilja, Gudmundsson, Julius, Johannesson, Ari J., Sturluson, Arni, Oddsson, Asmundur, Halldorsson, Bjarni, Ludviksson, Björn R., Ferkingstad, Egil, Ivarsdottir, Erna V., Sveinbjornsson, Gardar, Grondal, Gerdur, Masson, Gisli, Eldjarn, Grimur Hjorleifsson, Thorisson, Gudmundur A., Kristjansdottir, Katla, Knowlton, Kirk U., Moore, Kristjan H. S., Gudjonsson, Sigurjon A., Rognvaldsson, Solvi, Knight, Stacey, Nadauld, Lincoln D., Holm, Hilma, Magnusson, Olafur T., Sulem, Patrick, Gudbjartsson, Daniel F., Rafnar, Thorunn, Thorleifsson, Gudmar, Melsted, Pall, Norddahl, Gudmundur L., Jonsdottir, Ingileif, and Stefansson, Kari

Published
2024
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25. GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis

Author

Skuladottir, Astros Th., Stefansdottir, Lilja, Halldorsson, Gisli H., Stefansson, Olafur A., Bjornsdottir, Anna, Jonsson, Palmi, Palmadottir, Vala, Thorgeirsson, Thorgeir E., Walters, G. Bragi, Gisladottir, Rosa S., Bjornsdottir, Gyda, Jonsdottir, Gudrun A., Sulem, Patrick, Gudbjartsson, Daniel F., Knowlton, Kirk U., Jones, David A., Ottas, Aigar, Pedersen, Ole B., Didriksen, Maria, Brunak, Søren, Banasik, Karina, Hansen, Thomas Folkmann, Erikstrup, Christian, Haavik, Jan, Andreassen, Ole A., Rye, David, Igland, Jannicke, Ostrowski, Sisse Rye, Milani, Lili A., Nadauld, Lincoln D., Stefansson, Hreinn, and Stefansson, Kari

Published
2024
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26. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

Author

Scholz, Markus, Horn, Katrin, Pott, Janne, Wuttke, Matthias, Kühnapfel, Andreas, Nasr, M. Kamal, Kirsten, Holger, Li, Yong, Hoppmann, Anselm, Gorski, Mathias, Ghasemi, Sahar, Li, Man, Tin, Adrienne, Chai, Jin-Fang, Cocca, Massimiliano, Wang, Judy, Nutile, Teresa, Akiyama, Masato, Åsvold, Bjørn Olav, Bansal, Nisha, Biggs, Mary L., Boutin, Thibaud, Brenner, Hermann, Brumpton, Ben, Burkhardt, Ralph, Cai, Jianwen, Campbell, Archie, Campbell, Harry, Chalmers, John, Chasman, Daniel I., Chee, Miao Ling, Chee, Miao Li, Chen, Xu, Cheng, Ching-Yu, Cifkova, Renata, Daviglus, Martha, Delgado, Graciela, Dittrich, Katalin, Edwards, Todd L., Endlich, Karlhans, Michael Gaziano, J., Giri, Ayush, Giulianini, Franco, Gordon, Scott D., Gudbjartsson, Daniel F., Hallan, Stein, Hamet, Pavel, Hartman, Catharina A., Hayward, Caroline, Heid, Iris M., Hellwege, Jacklyn N., Holleczek, Bernd, Holm, Hilma, Hutri-Kähönen, Nina, Hveem, Kristian, Isermann, Berend, Jonas, Jost B., Joshi, Peter K., Kamatani, Yoichiro, Kanai, Masahiro, Kastarinen, Mika, Khor, Chiea Chuen, Kiess, Wieland, Kleber, Marcus E., Körner, Antje, Kovacs, Peter, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kuokkanen, Mikko, Kähönen, Mika, Lange, Leslie A., Lash, James P., Lehtimäki, Terho, Li, Hengtong, Lin, Bridget M., Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K. E., Martin, Nicholas G., Matsuda, Koichi, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., März, Winfried, Nauck, Matthias, Nikus, Kjell, Nolte, Ilja M., Noordam, Raymond, Okada, Yukinori, Olafsson, Isleifur, Oldehinkel, Albertine J., Penninx, Brenda W. J. H., Perola, Markus, Pirastu, Nicola, Polasek, Ozren, Porteous, David J., Poulain, Tanja, Psaty, Bruce M., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Rasheed, Humaira, Reilly, Dermot F., Rice, Kenneth M., Richmond, Anne, Ridker, Paul M., Rotter, Jerome I., Rudan, Igor, Sabanayagam, Charumathi, Salomaa, Veikko, Schneiderman, Neil, Schöttker, Ben, Sims, Mario, Snieder, Harold, Stark, Klaus J., Stefansson, Kari, Stocker, Hannah, Stumvoll, Michael, Sulem, Patrick, Sveinbjornsson, Gardar, Svensson, Per O., Tai, E-Shyong, Taylor, Kent D., Tayo, Bamidele O., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomas, Laurent F., Tremblay, Johanne, Tönjes, Anke, van der Most, Peter J., Vitart, Veronique, Völker, Uwe, Wang, Ya Xing, Wang, Chaolong, Wei, Wen Bin, Whitfield, John B., Wild, Sarah H., Wilson, James F., Winkler, Thomas W., Wong, Tien-Yin, Woodward, Mark, Sim, Xueling, Chu, Audrey Y., Feitosa, Mary F., Thorsteinsdottir, Unnur, Hung, Adriana M., Teumer, Alexander, Franceschini, Nora, Parsa, Afshin, Köttgen, Anna, Schlosser, Pascal, and Pattaro, Cristian

Published
2024
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27. Variant in the synaptonemal complex protein SYCE2 associates with pregnancy loss through effect on recombination

Author

Steinthorsdottir, Valgerdur, Halldorsson, Bjarni V., Jonsson, Hakon, Palsson, Gunnar, Oddsson, Asmundur, Westergaard, David, Arnadottir, Gudny A., Stefansdottir, Lilja, Banasik, Karina, Esplin, M. Sean, Hansen, Thomas Folkmann, Brunak, Søren, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Thorleifsson, Gudmar, Nadauld, Lincoln D., Haraldsson, Asgeir, Steingrimsdottir, Thora, Tryggvadottir, Laufey, Jonsdottir, Ingileif, Gudbjartsson, Daniel F., Hoffmann, Eva R., Sulem, Patrick, Holm, Hilma, Nielsen, Henriette Svarre, and Stefansson, Kari

Published
2024
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28. Stochastic Graphon Mean Field Games with Jumps and Approximate Nash Equilibria

Author

Amini, Hamed, Cao, Zhongyuan, and Sulem, Agnès

Subjects
Mathematics - Probability, Mathematics - Optimization and Control
Abstract

We study continuous stochastic games with inhomogeneous mean field interactions on large networks and explore their graphon limits. We consider a model with a continuum of players, where each player's dynamics involve not only mean field interactions but also individual jumps induced by a Poisson random measure. We examine the case of controlled dynamics, with control terms present in the drift, diffusion, and jump components. We introduce the graphon game model based on a graphon controlled stochastic differential equation (SDE) system with jumps, which can be regarded as the limiting case of a finite game's dynamic system as the number of players goes to infinity. Under some general assumptions, we establish the existence and uniqueness of Markovian graphon equilibria. We then provide convergence results on the state trajectories and their laws, transitioning from finite game systems to graphon systems. We also study approximate equilibria for finite games on large networks, using the graphon equilibrium as a benchmark. The rates of convergence are analyzed under various underlying graphon models and regularity assumptions., Comment: 37 pages

Published
2023

29. Loss-of-function variants in ITSN1 confer high risk of Parkinson’s disease

Author

Astros Th. Skuladottir, Vinicius Tragante, Gardar Sveinbjornsson, Hannes Helgason, Arni Sturluson, Anna Bjornsdottir, Palmi Jonsson, Vala Palmadottir, Olafur A. Sveinsson, Brynjar O. Jensson, Sigurjon A. Gudjonsson, Erna V. Ivarsdottir, Rosa S. Gisladottir, Arni F. Gunnarsson, G. Bragi Walters, Gudrun A. Jonsdottir, Thorgeir E. Thorgeirsson, Gyda Bjornsdottir, Hilma Holm, Daniel F. Gudbjartsson, Patrick Sulem, Hreinn Stefansson, and Kari Stefansson

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in ITSN1 and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson’s Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.

Published
2024
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30. Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Author

Molly Went, Laura Duran-Lozano, Gisli H. Halldorsson, Andrea Gunnell, Nerea Ugidos-Damboriena, Philip Law, Ludvig Ekdahl, Amit Sud, Gudmar Thorleifsson, Malte Thodberg, Thorunn Olafsdottir, Antton Lamarca-Arrizabalaga, Caterina Cafaro, Abhishek Niroula, Ram Ajore, Aitzkoa Lopez de Lapuente Portilla, Zain Ali, Maroulio Pertesi, Hartmut Goldschmidt, Lilja Stefansdottir, Sigurdur Y. Kristinsson, Simon N. Stacey, Thorvardur J. Love, Saemundur Rognvaldsson, Roman Hajek, Pavel Vodicka, Ulrika Pettersson-Kymmer, Florentin Späth, Carolina Schinke, Frits Van Rhee, Patrick Sulem, Egil Ferkingstad, Grimur Hjorleifsson Eldjarn, Ulf-Henrik Mellqvist, Ingileif Jonsdottir, Gareth Morgan, Pieter Sonneveld, Anders Waage, Niels Weinhold, Hauke Thomsen, Asta Försti, Markus Hansson, Annette Juul-Vangsted, Unnur Thorsteinsdottir, Kari Hemminki, Martin Kaiser, Thorunn Rafnar, Kari Stefansson, Richard Houlston, and Björn Nilsson

Subjects
Science
Abstract

Abstract Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.

Published
2024
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31. Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease

Author

Saedis Saevarsdottir, Kristbjörg Bjarnadottir, Thorsteinn Markusson, Jonas Berglund, Thorunn A. Olafsdottir, Gisli H. Halldorsson, Gudrun Rutsdottir, Kristbjorg Gunnarsdottir, Asgeir Orn Arnthorsson, Sigrun H. Lund, Lilja Stefansdottir, Julius Gudmundsson, Ari J. Johannesson, Arni Sturluson, Asmundur Oddsson, Bjarni Halldorsson, Björn R. Ludviksson, Egil Ferkingstad, Erna V. Ivarsdottir, Gardar Sveinbjornsson, Gerdur Grondal, Gisli Masson, Grimur Hjorleifsson Eldjarn, Gudmundur A. Thorisson, Katla Kristjansdottir, Kirk U. Knowlton, Kristjan H. S. Moore, Sigurjon A. Gudjonsson, Solvi Rognvaldsson, Stacey Knight, Lincoln D. Nadauld, Hilma Holm, Olafur T. Magnusson, Patrick Sulem, Daniel F. Gudbjartsson, Thorunn Rafnar, Gudmar Thorleifsson, Pall Melsted, Gudmundur L. Norddahl, Ingileif Jonsdottir, and Kari Stefansson

Subjects
Science
Abstract

Abstract Autoimmune thyroid disease (AITD) is a common autoimmune disease. In a GWAS meta-analysis of 110,945 cases and 1,084,290 controls, 290 sequence variants at 225 loci are associated with AITD. Of these variants, 115 are previously unreported. Multiomics analysis yields 235 candidate genes outside the MHC-region and the findings highlight the importance of genes involved in T-cell regulation. A rare 5’-UTR variant (rs781745126-T, MAF = 0.13% in Iceland) in LAG3 has the largest effect (OR = 3.42, P = 2.2 × 10−16) and generates a novel start codon for an open reading frame upstream of the canonical protein translation initiation site. rs781745126-T reduces mRNA and surface expression of the inhibitory immune checkpoint LAG-3 co-receptor on activated lymphocyte subsets and halves LAG-3 levels in plasma among heterozygotes. All three homozygous carriers of rs781745126-T have AITD, of whom one also has two other T-cell mediated diseases, that is vitiligo and type 1 diabetes. rs781745126-T associates nominally with vitiligo (OR = 5.1, P = 6.5 × 10−3) but not with type 1 diabetes. Thus, the effect of rs781745126-T is akin to drugs that inhibit LAG-3, which unleash immune responses and can have thyroid dysfunction and vitiligo as adverse events. This illustrates how a multiomics approach can reveal potential drug targets and safety concerns.

Published
2024
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32. Ruin Probabilities for Risk Processes in Stochastic Networks

Author

Amini, Hamed, Cao, Zhongyuan, Minca, Andreea, and Sulem, Agnès

Subjects
Mathematics - Probability, Quantitative Finance - Risk Management, 91B05, 91G45, 60C05
Abstract

We study multidimensional Cram\'er-Lundberg risk processes where agents, located on a large sparse network, receive losses form their neighbors. To reduce the dimensionality of the problem, we introduce classification of agents according to an arbitrary countable set of types. The ruin of any agent triggers losses for all of its neighbours. We consider the case when the loss arrival process induced by the ensemble of ruined agents follows a Poisson process with general intensity function that scales with the network size. When the size of the network goes to infinity, we provide explicit ruin probabilities at the end of the loss propagation process for agents of any type. These limiting probabilities depend, in addition to the agents' types and the network structure, on the loss distribution and the loss arrival process. For a more complex risk processes on open networks, when in addition to the internal networked risk processes the agents receive losses from external users, we provide bounds on ruin probabilities., Comment: 31 pages

Published
2023

33. Scalable and adaptive variational Bayes methods for Hawkes processes

Author

Sulem, Deborah, Rivoirard, Vincent, and Rousseau, Judith

Subjects
Mathematics - Statistics Theory, Statistics - Machine Learning
Abstract

Hawkes processes are often applied to model dependence and interaction phenomena in multivariate event data sets, such as neuronal spike trains, social interactions, and financial transactions. In the nonparametric setting, learning the temporal dependence structure of Hawkes processes is generally a computationally expensive task, all the more with Bayesian estimation methods. In particular, for generalised nonlinear Hawkes processes, Monte-Carlo Markov Chain methods applied to compute the doubly intractable posterior distribution are not scalable to high-dimensional processes in practice. Recently, efficient algorithms targeting a mean-field variational approximation of the posterior distribution have been proposed. In this work, we first unify existing variational Bayes approaches under a general nonparametric inference framework, and analyse the asymptotic properties of these methods under easily verifiable conditions on the prior, the variational class, and the nonlinear model. Secondly, we propose a novel sparsity-inducing procedure, and derive an adaptive mean-field variational algorithm for the popular sigmoid Hawkes processes. Our algorithm is parallelisable and therefore computationally efficient in high-dimensional setting. Through an extensive set of numerical simulations, we also demonstrate that our procedure is able to adapt to the dimensionality of the parameter of the Hawkes process, and is partially robust to some type of model mis-specification.

Published
2022

34. Gyrofluid simulations of turbulence and reconnection in space plasmas

Author

T. Passot, S.S. Cerri, C. Granier, D. Laveder, P.L. Sulem, and E. Tassi

Subjects
Collisionless plasmas, Alfvenic turbulence, Magnetic reconnection, Gyrofluids, Plasma physics. Ionized gases, QC717.6-718.8, Science
Abstract

A Hamiltonian two-field gyrofluid model is used to investigate the dynamics of an electron-ion collisionless plasma subject to a strong ambient magnetic field, within a spectral range extending from the magnetohydrodynamic (MHD) scales to the electron skin depth. This model isolates Alfvén, Kinetic Alfvén and Inertial Kinetic Alfvén waves that play a central role in space plasmas, and extends standard reduced fluid models to broader ranges of the plasma parameters. Recent numerical results are reviewed, including (i) the reconnection-mediated MHD turbulence developing from the collision of counter-propagating Alfvén wave packets, (ii) the specific features of the cascade dynamics in strongly imbalanced turbulence, including a possible link between the existence of a spectral transition range and the presence of co-propagating wave interactions at sub-ion scales, for which new simulations are reported, (iii) the influence of the ion-to-electron temperature ratio in two-dimensional collisionless magnetic reconnection. The role of electron finite Larmor radius corrections is pointed out and the extension of the present model to a four-field gyrofluid model is discussed. Such an extended model accurately describes electron finite Larmor radius effects at small or moderate values of the electron beta parameter, and also retains the coupling to slow magnetosonic waves.

Published
2024
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35. A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome

Author

Klemenzdottir, Elin Ola, Arnadottir, Gudny Anna, Jensson, Brynjar Orn, Jonasdottir, Adalbjorg, Katrinardottir, Hildigunnur, Fridriksdottir, Run, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Gudjonsson, Sigurjon Axel, Jonsson, Jon Johannes, Stefansdottir, Vigdis, Danielsen, Ragnar, Palsdottir, Astridur, Jonsson, Hakon, Helgason, Agnar, Magnusson, Olafur Thor, Thorsteinsdottir, Unnur, Bjornsson, Hans Tomas, Stefansson, Kari, and Sulem, Patrick

Published
2024
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37. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.

Published
2024
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38. Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis

Author

Stacey, Simon N., Zink, Florian, Halldorsson, Gisli H., Stefansdottir, Lilja, Gudjonsson, Sigurjon A., Einarsson, Gudmundur, Hjörleifsson, Grimur, Eiriksdottir, Thjodbjorg, Helgadottir, Anna, Björnsdottir, Gyda, Thorgeirsson, Thorgeir E., Olafsdottir, Thorunn A., Jonsdottir, Ingileif, Gretarsdottir, Solveig, Tragante, Vinicius, Magnusson, Magnus K., Jonsson, Hakon, Gudmundsson, Julius, Olafsson, Sigurgeir, Holm, Hilma, Gudbjartsson, Daniel F., Sulem, Patrick, Helgason, Agnar, Thorsteinsdottir, Unnur, Tryggvadottir, Laufey, Rafnar, Thorunn, Melsted, Pall, Ulfarsson, Magnus Ö., Vidarsson, Brynjar, Thorleifsson, Gudmar, and Stefansson, Kari

Published
2023
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40. GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis

Author

Astros Th. Skuladottir, Lilja Stefansdottir, Gisli H. Halldorsson, Olafur A. Stefansson, Anna Bjornsdottir, Palmi Jonsson, Vala Palmadottir, Thorgeir E. Thorgeirsson, G. Bragi Walters, Rosa S. Gisladottir, Gyda Bjornsdottir, Gudrun A. Jonsdottir, Patrick Sulem, Daniel F. Gudbjartsson, Kirk U. Knowlton, David A. Jones, Aigar Ottas, Estonian Biobank, Ole B. Pedersen, Maria Didriksen, Søren Brunak, Karina Banasik, Thomas Folkmann Hansen, Christian Erikstrup, DBDS Genomic Consortium, Jan Haavik, Ole A. Andreassen, David Rye, Jannicke Igland, Sisse Rye Ostrowski, Lili A. Milani, Lincoln D. Nadauld, Hreinn Stefansson, and Kari Stefansson

Subjects
Biology (General), QH301-705.5
Abstract

Abstract Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Published
2024
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41. Turbulent regimes in collisions of 3D Alfv\'en-wave packets

Author

Cerri, Silvio Sergio, Passot, Thierry, Laveder, Dimitri, Sulem, Pierre-Louis, and Kunz, Matthew W.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Physics - Fluid Dynamics, Physics - Plasma Physics, Physics - Space Physics
Abstract

Using 3D gyrofluid simulations, we revisit the problem of Alfven-wave (AW) collisions as building blocks of the Alfvenic cascade and their interplay with magnetic reconnection at magnetohydrodynamic (MHD) scales. Depending on the large-scale nonlinearity parameter $\chi_0$ (the ratio between AW linear propagation time and nonlinear turnover time), different regimes are observed. For strong nonlinearities ($\chi_0\sim1$), turbulence is consistent with a dynamically aligned, critically balanced cascade--fluctuations exhibit a scale-dependent alignment $\sin\theta_k\propto k_\perp^{-1/4}$, a $k_\perp^{-3/2}$ spectrum and $k_\|\propto k_\perp^{1/2}$ spectral anisotropy. At weaker nonlinearities (small $\chi_0$), a spectral break marking the transition between a large-scale weak regime and a small-scale $k_\perp^{-11/5}$ tearing-mediated range emerges, implying that dynamic alignment occurs also for weak nonlinearities. At $\chi_0<1$ the alignment angle $\theta_{k_\perp}$ shows a stronger scale dependence than in the $\chi_0\sim1$ regime, i.e. $\sin\theta_k\propto k_\perp^{-1/2}$ at $\chi_0\sim0.5$, and $\sin\theta_k\propto k_\perp^{-1}$ at $\chi_0\sim0.1$. Dynamic alignment in the weak regime also modifies the large-scale spectrum, scaling roughly as $k_\perp^{-3/2}$ for $\chi_0\sim0.5$ and as $k_\perp^{-1}$ for $\chi_0\sim0.1$. A phenomenological theory of dynamically aligned turbulence at weak nonlinearities that can explain these spectra and the transition to the tearing-mediated regime is provided; at small $\chi_0$, the strong scale dependence of the alignment angle combines with the increased lifetime of turbulent eddies to allow tearing to onset and mediate the cascade at scales that can be larger than those predicted for a critically balanced cascade by several orders of magnitude. Such a transition to tearing-mediated turbulence may even supplant the usual weak-to-strong transition., Comment: 13 pages, 5 figures, 1 table; accepted for publication in The Astrophysical Journal

Published
2022
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42. Patented technologies in the extraction, preservation, and application of anthocyanins in food: A review

Author

Sulem Yali Granados-Balbuena, Vanesa Chicatto-Gasperín, Ericka Santacruz-Juárez, Erik Ocaranza-Sánchez, Carolina Ramírez-López, María Guadalupe García-Meza, Lilia Tapia-López, Raúl René Robles de la Torre, and María Reyna Robles López

Subjects
Anthocyanins, Patents, Application, Food, Natural colorants, Technology, Food processing and manufacture, TP368-456
Abstract

Color is an important parameter in food because it can be associated with quality. Since ancient times, natural dyes have been used in foods to make them attractive, but due to their poor stability to environmental factors and production processes, technologies emerged over time that led to getting artificial pigments with high stability, low production costs, and high dyeing capacity. However, some adverse indications of health damage have been reported, and that is why there is a growing interest in using natural colorants in food again. The red color is one of the most striking and important tones in the food sector since it is attractive, and it can produce expected taste sensations. One of the natural pigments that provide this red hue are anthocyanins, compounds that are widely distributed in plant sources, unlike artificial colors, have been associated with multiple health benefits. However, the application of anthocyanins represents a challenge due to their low stability against factors such as pH, oxygen, light, and temperature, so they are being stabilized through chemistry or physics way. This work aims to highlight the importance of anthocyanins and illustrate a summary of stabilization and conservation strategies used in patents applied in the food industry, as a methodological background to increase the use of natural pigments in diets.

Published
2024
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43. Direct kinetic Alfv\'en wave energy cascade in the presence of imbalance

Author

Passot, T., Sulem, P. L., and Laveder, D.

Subjects
Physics - Space Physics
Abstract

A two-field Hamiltonian gyrofluid model for kinetic Alfv\'en waves retaining ion finite Larmor radius corrections and parallel magnetic field fluctuations is used to study direct turbulent cascades from the MHD to the sub-ion scales. For moderate energy imbalance and weak enough magnetic fluctuations, the spectrum of the transverse magnetic field and that of the most energetic wave display a steep transition zone near the ion scale, while the parallel transfer (and thus the parallel dissipation) remains weak. In this regime, the perpendicular flux of generalized cross helicity displays a significant decay past the ion scale, while the perpendicular energy flux remains almost constant. A phenomenological model suggests that the interactions between co-propagative waves present at the sub-ion scales can play a central role in the development of a transition zone in the presence of a helicity barrier., Comment: 17 pages, 12 figures

Published
2022
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44. A Hamiltonian Dysthe equation for deep-water gravity waves with constant vorticity

Author

Guyenne, Philippe, Kairzhan, Adilbek, and Sulem, Catherine

Subjects
Mathematics - Analysis of PDEs, 76B15, 35Q55
Abstract

This paper is a study of the water wave problem in a two-dimensional domain of infinite depth in the presence of nonzero constant vorticity. A goal is to describe the effects of uniform shear flow on the modulation of weakly nonlinear quasi-monochromatic surface gravity waves. Starting from the Hamiltonian formulation of this problem and using techniques from Hamiltonian transformation theory, we derive a Hamiltonian Dysthe equation for the time evolution of the wave envelope. Consistent with previous studies, we observe that the uniform shear flow tends to enhance or weaken the modulational instability of Stokes waves depending on its direction and strength. Our method also provides a non-perturbative procedure to reconstruct the surface elevation from the wave envelope, based on the Birkhoff normal form transformation to eliminate all non-resonant triads. This model is tested against direct numerical simulations of the full Euler equations and against a related Dysthe equation recently derived by Curtis, Carter and Kalisch (J. Fluid Mech. 855, 2018) in the context of constant vorticity. Very good agreement is found for a range of values of the vorticity.

Published
2022
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45. Graph similarity learning for change-point detection in dynamic networks

Author

Sulem, Deborah, Kenlay, Henry, Cucuringu, Mihai, and Dong, Xiaowen

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning, Quantitative Finance - Statistical Finance, Statistics - Applications, Statistics - Methodology
Abstract

Dynamic networks are ubiquitous for modelling sequential graph-structured data, e.g., brain connectome, population flows and messages exchanges. In this work, we consider dynamic networks that are temporal sequences of graph snapshots, and aim at detecting abrupt changes in their structure. This task is often termed network change-point detection and has numerous applications, such as fraud detection or physical motion monitoring. Leveraging a graph neural network model, we design a method to perform online network change-point detection that can adapt to the specific network domain and localise changes with no delay. The main novelty of our method is to use a siamese graph neural network architecture for learning a data-driven graph similarity function, which allows to effectively compare the current graph and its recent history. Importantly, our method does not require prior knowledge on the network generative distribution and is agnostic to the type of change-points; moreover, it can be applied to a large variety of networks, that include for instance edge weights and node attributes. We show on synthetic and real data that our method enjoys a number of benefits: it is able to learn an adequate graph similarity function for performing online network change-point detection in diverse types of change-point settings, and requires a shorter data history to detect changes than most existing state-of-the-art baselines., Comment: 33 pages, 21 figures, 5 tables

Published
2022

46. Diverse Counterfactual Explanations for Anomaly Detection in Time Series

Author

Sulem, Deborah, Donini, Michele, Zafar, Muhammad Bilal, Aubet, Francois-Xavier, Gasthaus, Jan, Januschowski, Tim, Das, Sanjiv, Kenthapadi, Krishnaram, and Archambeau, Cedric

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Data-driven methods that detect anomalies in times series data are ubiquitous in practice, but they are in general unable to provide helpful explanations for the predictions they make. In this work we propose a model-agnostic algorithm that generates counterfactual ensemble explanations for time series anomaly detection models. Our method generates a set of diverse counterfactual examples, i.e, multiple perturbed versions of the original time series that are not considered anomalous by the detection model. Since the magnitude of the perturbations is limited, these counterfactuals represent an ensemble of inputs similar to the original time series that the model would deem normal. Our algorithm is applicable to any differentiable anomaly detection model. We investigate the value of our method on univariate and multivariate real-world datasets and two deep-learning-based anomaly detection models, under several explainability criteria previously proposed in other data domains such as Validity, Plausibility, Closeness and Diversity. We show that our algorithm can produce ensembles of counterfactual examples that satisfy these criteria and thanks to a novel type of visualisation, can convey a richer interpretation of a model's internal mechanism than existing methods. Moreover, we design a sparse variant of our method to improve the interpretability of counterfactual explanations for high-dimensional time series anomalies. In this setting, our explanation is localised on only a few dimensions and can therefore be communicated more efficiently to the model's user., Comment: 24 pages, 11 figures

Published
2022

47. Author Correction: Large-scale plasma proteomics comparisons through genetics and disease associations

Author

Eldjarn, Grimur Hjorleifsson, Ferkingstad, Egil, Lund, Sigrun H., Helgason, Hannes, Magnusson, Olafur Th., Gunnarsdottir, Kristbjorg, Olafsdottir, Thorunn A., Halldorsson, Bjarni V., Olason, Pall I., Zink, Florian, Gudjonsson, Sigurjon A., Sveinbjornsson, Gardar, Magnusson, Magnus I., Helgason, Agnar, Oddsson, Asmundur, Halldorsson, Gisli H., Magnusson, Magnus K., Saevarsdottir, Saedis, Eiriksdottir, Thjodbjorg, Masson, Gisli, Stefansson, Hreinn, Jonsdottir, Ingileif, Holm, Hilma, Rafnar, Thorunn, Melsted, Pall, Saemundsdottir, Jona, Norddahl, Gudmundur L., Thorleifsson, Gudmar, Ulfarsson, Magnus O., Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Sulem, Patrick, and Stefansson, Kari

Published
2024
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48. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

Author

Markus Scholz, Katrin Horn, Janne Pott, Matthias Wuttke, Andreas Kühnapfel, M. Kamal Nasr, Holger Kirsten, Yong Li, Anselm Hoppmann, Mathias Gorski, Sahar Ghasemi, Man Li, Adrienne Tin, Jin-Fang Chai, Massimiliano Cocca, Judy Wang, Teresa Nutile, Masato Akiyama, Bjørn Olav Åsvold, Nisha Bansal, Mary L. Biggs, Thibaud Boutin, Hermann Brenner, Ben Brumpton, Ralph Burkhardt, Jianwen Cai, Archie Campbell, Harry Campbell, John Chalmers, Daniel I. Chasman, Miao Ling Chee, Miao Li Chee, Xu Chen, Ching-Yu Cheng, Renata Cifkova, Martha Daviglus, Graciela Delgado, Katalin Dittrich, Todd L. Edwards, Karlhans Endlich, J. Michael Gaziano, Ayush Giri, Franco Giulianini, Scott D. Gordon, Daniel F. Gudbjartsson, Stein Hallan, Pavel Hamet, Catharina A. Hartman, Caroline Hayward, Iris M. Heid, Jacklyn N. Hellwege, Bernd Holleczek, Hilma Holm, Nina Hutri-Kähönen, Kristian Hveem, Berend Isermann, Jost B. Jonas, Peter K. Joshi, Yoichiro Kamatani, Masahiro Kanai, Mika Kastarinen, Chiea Chuen Khor, Wieland Kiess, Marcus E. Kleber, Antje Körner, Peter Kovacs, Alena Krajcoviechova, Holly Kramer, Bernhard K. Krämer, Mikko Kuokkanen, Mika Kähönen, Leslie A. Lange, James P. Lash, Terho Lehtimäki, Hengtong Li, Bridget M. Lin, Jianjun Liu, Markus Loeffler, Leo-Pekka Lyytikäinen, Patrik K. E. Magnusson, Nicholas G. Martin, Koichi Matsuda, Yuri Milaneschi, Pashupati P. Mishra, Nina Mononen, Grant W. Montgomery, Dennis O. Mook-Kanamori, Josyf C. Mychaleckyj, Winfried März, Matthias Nauck, Kjell Nikus, Ilja M. Nolte, Raymond Noordam, Yukinori Okada, Isleifur Olafsson, Albertine J. Oldehinkel, Brenda W. J. H. Penninx, Markus Perola, Nicola Pirastu, Ozren Polasek, David J. Porteous, Tanja Poulain, Bruce M. Psaty, Ton J. Rabelink, Laura M. Raffield, Olli T. Raitakari, Humaira Rasheed, Dermot F. Reilly, Kenneth M. Rice, Anne Richmond, Paul M. Ridker, Jerome I. Rotter, Igor Rudan, Charumathi Sabanayagam, Veikko Salomaa, Neil Schneiderman, Ben Schöttker, Mario Sims, Harold Snieder, Klaus J. Stark, Kari Stefansson, Hannah Stocker, Michael Stumvoll, Patrick Sulem, Gardar Sveinbjornsson, Per O. Svensson, E-Shyong Tai, Kent D. Taylor, Bamidele O. Tayo, Andrej Teren, Yih-Chung Tham, Joachim Thiery, Chris H. L. Thio, Laurent F. Thomas, Johanne Tremblay, Anke Tönjes, Peter J. van der Most, Veronique Vitart, Uwe Völker, Ya Xing Wang, Chaolong Wang, Wen Bin Wei, John B. Whitfield, Sarah H. Wild, James F. Wilson, Thomas W. Winkler, Tien-Yin Wong, Mark Woodward, Xueling Sim, Audrey Y. Chu, Mary F. Feitosa, Unnur Thorsteinsdottir, Adriana M. Hung, Alexander Teumer, Nora Franceschini, Afshin Parsa, Anna Köttgen, Pascal Schlosser, and Cristian Pattaro

Subjects
Science
Abstract

Abstract X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.

Published
2024
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49. EMOTHAW: A novel database for emotional state recognition from handwriting

Author

Likforman-Sulem, Laurence, Esposito, Anna, Faundez-Zanuy, Marcos, Clemençon, Stephan, and Cordasco, Gennaro

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

The detection of negative emotions through daily activities such as handwriting is useful for promoting well-being. The spread of human-machine interfaces such as tablets makes the collection of handwriting samples easier. In this context, we present a first publicly available handwriting database which relates emotional states to handwriting, that we call EMOTHAW. This database includes samples of 129 participants whose emotional states, namely anxiety, depression and stress, are assessed by the Depression Anxiety Stress Scales (DASS) questionnaire. Seven tasks are recorded through a digitizing tablet: pentagons and house drawing, words copied in handprint, circles and clock drawing, and one sentence copied in cursive writing. Records consist in pen positions, on-paper and in-air, time stamp, pressure, pen azimuth and altitude. We report our analysis on this database. From collected data, we first compute measurements related to timing and ductus. We compute separate measurements according to the position of the writing device: on paper or in-air. We analyse and classify this set of measurements (referred to as features) using a random forest approach. This latter is a machine learning method [2], based on an ensemble of decision trees, which includes a feature ranking process. We use this ranking process to identify the features which best reveal a targeted emotional state. We then build random forest classifiers associated to each emotional state. Our results, obtained from cross-validation experiments, show that the targeted emotional states can be identified with accuracies ranging from 60% to 71%., Comment: 31 pages

Published
2022
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50. Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Author

Bjornsdottir, Gyda, Chalmer, Mona A., Stefansdottir, Lilja, Skuladottir, Astros Th., Einarsson, Gudmundur, Andresdottir, Margret, Beyter, Doruk, Ferkingstad, Egil, Gretarsdottir, Solveig, Halldorsson, Bjarni V., Halldorsson, Gisli H., Helgadottir, Anna, Helgason, Hannes, Hjorleifsson Eldjarn, Grimur, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Jonsdottir, Ingileif, Knowlton, Kirk U., Nadauld, Lincoln D., Lund, Sigrun H., Magnusson, Olafur Th., Melsted, Pall, Moore, Kristjan H. S., Oddsson, Asmundur, Olason, Pall I., Sigurdsson, Asgeir, Stefansson, Olafur A., Saemundsdottir, Jona, Sveinbjornsson, Gardar, Tragante, Vinicius, Unnsteinsdottir, Unnur, Walters, G. Bragi, Zink, Florian, Rødevand, Linn, Andreassen, Ole A., Igland, Jannicke, Lie, Rolv T., Haavik, Jan, Banasik, Karina, Brunak, Søren, Didriksen, Maria, T. Bruun, Mie, Erikstrup, Christian, Kogelman, Lisette J. A., Nielsen, Kaspar R., Sørensen, Erik, Pedersen, Ole B., Ullum, Henrik, Masson, Gisli, Thorsteinsdottir, Unnur, Olesen, Jes, Ludvigsson, Petur, Thorarensen, Olafur, Bjornsdottir, Anna, Sigurdardottir, Gudrun R., Sveinsson, Olafur A., Ostrowski, Sisse R., Holm, Hilma, Gudbjartsson, Daniel F., Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Hreinn, Thorgeirsson, Thorgeir E., Hansen, Thomas F., and Stefansson, Kari

Published
2023
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