Publications

H3K27me3 spreading organizes canonical PRC1 chromatin architecture to
regulate developmental programs
Brian Krug
Bo Hu
Haifen Chen
Adam Ptack
Xiao Chen
Kristjan H. Gretarsson
Shriya Deshmukh
Nisha Kabir
Augusto Faria Andrade
Elias Jabbour
Ashot S. Harutyunyan
John J. Y. Lee
Maud Hulswit
Damien Faury
Caterina Russo
Xinjing Xu
Michael J. Johnston
Audrey Baguette
Nathan A. Dahl
Alexander G. Weil … (see 12 more)
Benjamin Ellezam
Rola Dali
Khadija Wilson
Benjamin A. Garcia
Rajesh Kumar Soni
Marco Gallo
Michael D. Taylor
Claudia L. Kleinman
Jacek Majewski
Nada Jabado
Chao Lu
Polycomb Repressive Complex 2 (PRC2)-mediated histone H3K27 tri-methylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochr… (see more)omatin. In early development, polycomb-regulated genes are connected through long-range 3D interactions which resolve upon differentiation. Here, we report that polycomb looping is controlled by H3K27me3 spreading and regulates target gene silencing and cell fate specification. Using glioma-derived H3 Lys-27-Met (H3K27M) mutations as tools to restrict H3K27me3 deposition, we show that H3K27me3 confinement concentrates the chromatin pool of cPRC1, resulting in heightened 3D interactions mirroring chromatin architecture of pluripotency, and stringent gene repression that maintains cells in progenitor states to facilitate tumor development. Conversely, H3K27me3 spread in pluripotent stem cells, following neural differentiation or loss of the H3K36 methyltransferase NSD1, dilutes cPRC1 concentration and dissolves polycomb loops. These results identify the regulatory principles and disease implications of polycomb looping and nominate histone modification-guided distribution of reader complexes as an important mechanism for nuclear compartment organization. The confinement of H3K27me3 at PRC2 nucleation sites without its spreading correlates with increased 3D chromatin interactions. The H3K27M oncohistone concentrates canonical PRC1 that anchors chromatin loop interactions in gliomas, silencing developmental programs. Stem and progenitor cells require factors promoting H3K27me3 confinement, including H3K36me2, to maintain cPRC1 loop architecture. The cPRC1-H3K27me3 interaction is a targetable driver of aberrant self-renewal in tumor cells.
Harnessing TCR/CAR Antagonism to Enhance Immunotherapeutic Precision
Taisuke Kondo
François X. P. Bourassa
Sooraj R. Achar
Justyn DuSold
Pablo Cespedes
Madison Wahlsten
Audun Kvalvaag
Guillaume Gaud
Paul E. Love
Michael Dustin
Grégoire Altan-Bonnet
Naomi Taylor
Learning few-shot imitation as cultural transmission
Avishkar Bhoopchand
Bethanie Brownfield
Adrian Collister
Agustin Dal Lago
Ashley Edwards
Richard Everett
Alexandre Fréchette
Yanko Gitahy Oliveira
Edward Hughes
Kory Mathewson
Piermaria Mendolicchio
Julia Pawar
Miruna Pȋslar
Alex Platonov
Evan Senter
Sukhdeep Singh
Alexander Zacherl
Lei M Zhang
Room-temperature correlated states in twisted bilayer MoS$_2$
Fanfan Wu
Qiaoling Xu
Qinqin Wang
Yanbang Chu
Li Li
Jieying Liu
Jinpeng Tian
Yiru Ji
Le Liu
Yalong Yuan
Zhiheng Huang
Jiaojiao Zhao
Xiaozhou Zan
Kenji Watanabe
Takashi Taniguchi
Dongxia Shi
Gangxu Gu
Yang Xu
Lede Xian … (see 3 more)
Wei Yang
Luojun Du
Guangyu Zhang
Symmetry Breaking and Equivariant Neural Networks
Sékou-Oumar Kaba
Using symmetry as an inductive bias in deep learning has been proven to be a principled approach for sample-efficient model design. However,… (see more) the relationship between symmetry and the imperative for equivariance in neural networks is not always obvious. Here, we analyze a key limitation that arises in equivariant functions: their incapacity to break symmetry at the level of individual data samples. In response, we introduce a novel notion of 'relaxed equivariance' that circumvents this limitation. We further demonstrate how to incorporate this relaxation into equivariant multilayer perceptrons (E-MLPs), offering an alternative to the noise-injection method. The relevance of symmetry breaking is then discussed in various application domains: physics, graph representation learning, combinatorial optimization and equivariant decoding.
On the Information Geometry of Vision Transformers
On the Varied Faces of Overparameterization in Supervised and Self-Supervised Learning
Matteo Gamba
Blake Aaron Richards
Agrawal
Hossein Azizpour
Mårten Björkman
The quality of the representations learned by neural networks depends on several factors, including the loss function, learning algorithm, a… (see more)nd model architecture. In this work, we use information geometric measures to assess the representation quality in a principled manner. We demonstrate that the sensitivity of learned representations to input perturbations, measured by the spectral norm of the feature Jacobian, provides valuable information about downstream generalization. On the other hand, measuring the coefficient of spectral decay observed in the eigenspectrum of feature covariance provides insights into the global representation geometry. First, we empirically establish an equivalence between these notions of representation quality and show that they are inversely correlated. Second, our analysis reveals the varying roles that overparameterization plays in improving generalization. Unlike supervised learning, we observe that increasing model width leads to higher discriminability and less smoothness in the self-supervised regime. Furthermore, we report that there is no observable double descent phenomenon in SSL with non-contrastive objectives for commonly used parameterization regimes, which opens up new opportunities for tight asymptotic analysis. Taken together, our results provide a loss-aware characterization of the different role of overparameterization in supervised and self-supervised learning.
1351. Predictors of Loss of Infectivity Among Healthcare Workers with Primary and Recurrent SARS-CoV-2 infection: An Observational Cohort Study
Stefka Dzieciolowska
Yves Longtin
Hugues Charest
Tonya Roy
Judith Fafard
Inès Levade
Jean Longtin
Leighanne Parkes
Jasmin Villeneuve
Patrice Savard
J. Corbeil
Gaston De Serres
Abstract Background Factors associated with loss of infectivity in healthcare workers (HCWs) with COVID-19 are poorly understood. Understand… (see more)ing predictive factors could help optimize return-to-work criteria and minimize absenteeism. Methods Prospective observational cohort study of HCWs with COVID-19 conducted between Feb 20 2022 and March 6 2023 in 20 institutions in Montreal, Canada, with clinical/laboratory follow-up on Day 5, 7 and 10 of infection. Infectivity was determined by viral culture (Vero E6 cells) on nasopharyngeal swabs. Predictors of loss of infectivity were investigated by univariate and multivariate logistic regression. Results Overall, 121 participants (79.3% female, mean age 40 years) were recruited. Most (n=107, 88.4%) had received ≥3 vaccines and 20 (16.5%) had a history of prior COVID-19. The proportion of HCWs with a positive viral culture decreased from 71.9% on day 5 of infection to 18.2% on day 10. The proportion of HCWs with a positive RT-PCR decreased from 93.3% (112/120) on day 5 (median Ct value, 23.4 [IQR, 20.6-27.9]) to 61.2% (74/120) on day 10 (median Ct value, 32.5 [IQR, 28.5 to undetectable]). Rapid antigen detection test (RADT) positivity decreased from 81.5% on day 5 to 34.2% on day 10. Participants with recurrent COVID-19 had lower likelihood of infectivity at each visit (OR on day 5, 0.14; 95% CI 0.05-0.40; p 0.001; OR on day 7, 0.04; 95% CI, 0.01-0.33; p=0.003) and none were infective on day 10 (p=0.02). At each visit, recurrent cases had higher median RT-PCR Ct values than primary infections (p 0.03) and were more likely to have a negative RADT result (p 0.01). By multivariate analysis, ongoing infectivity was associated with a RT-PCR Ct value 23 (adjusted OR [aOR] on day 5, 22.75; p 0.001; aOR on Day 7, 182.30; p 0.001; and aOR on Day 10; 24.71; p=0.02). A history of previous COVID-19 was associated with a lower probability of infectivity on Day 5 (aOR, 0.005; p=0.003). By contrast, symptom improvement (including fever) and RADT result were not independent predictors of loss of infectivity. Conclusion A lower RT-PCR Ct value is associated with ongoing infectivity, whereas COVID-19 reinfection is a predictor of loss of infectivity. These findings could help optimize return-to-work algorithms. Disclosures All Authors: No reported disclosures
Author Correction: 30×30 biodiversity gains rely on national coordination
Isaac Eckert
Andrea Brown
Dominique Caron
Federico Riva
Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications
Aline Lefebvre
Nicolas Traut
Amandine Pedoux
Anna Maruani
Anita Beggiato
Monique Elmaleh
David Germanaud
Anouck Amestoy
Myriam Ly‐Le Moal
Christopher H. Chatham
Lorraine Murtagh
Manuel Bouvard
Marianne Alisson
Marion Leboyer
Thomas Bourgeron
Roberto Toro
Clara A. Moreau
Richard Delorme
scGeneRythm: Using Neural Networks and Fourier Transformation to Cluster Genes by Time-Frequency Patterns in Single-Cell Data
Yiming Jia
Hao Wu
The search for the lost attractor
Mario Pasquato
Syphax Haddad
Pierfrancesco Di Cintio
Mircea Petrache
Ugo Niccolò Di Carlo
Alessandro Alberto Trani