Publications

Unraveling the Mysteries of Galaxy Clusters: Recurrent Inference Deconvolution of X-ray Spectra
C. Rhea
Julie Hlavacek-larrondo
Ralph P. Kraft
Ákos Bogdán
Alexandre Adam
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 Johnston
Audrey Baguette
Nathan A. Dahl
Alexander G. Weil … (voir 12 de plus)
Benjamin Ellezam
Rola Dali
Khadija Wilson
Benjamin A. Garcia
Rajesh Kumar Soni
Marco Gallo
Michael D. Taylor
Claudia Kleinman
Jacek Majewski
Nada Jabado
Chao Lu
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
Identification of Acute Myeloid Leukemia Cell Surface Therapeutic Targets Using Single Cell RNA Sequencing Supported By Surface Proteomics
Véronique Lisi
Banafsheh Khakipoor
Azer Farah
Marie-Eve Bordeleau
Éric Audemard
Arnaud Metois
Louis Theret
Jean-Francois Spinella
Jalila Chagraoui
Ossama Moujaber
Laure Mallinger
Isabel Boivin
Nadine Mayotte
Azadeh Hajmirza
Eric Bonneil
Francois Béliveau
Albert Feghali
Geneviève Boucher
Patrick Gendron
Frederic Barabe … (voir 6 de plus)
Guillaume Richard-Carpentier
Josée Hébert
Philippe Roux
Guy Sauvageau
Vincent-Philippe Lavallee
Background: Acute myeloid leukemia (AML) comprises diverse genomic subgroups and remains hard to treat in most patients. Despite breakthrou… (voir plus)ghs in the therapeutic arsenal in recent years, clinical usage of therapeutic antibodies or chimeric antigen receptor T (CAR-T) cells has been lagging in contrast to other hematological malignancies. In fact, CD33 represents the only antibody-based strategy approved for this disease to date, highlighting the need to identify new promising targets. AML cells span a wide range of aberrant myeloid differentiation programs, complexifying the identification, by bulk genomics, of targets expressed in the most immature leukemic cells. Aims and Methods: To identify the expression landscape of surface proteins in immature leukemic cells, we performed single-cell RNA sequencing (scRNA-seq, 10x 3' Reagent Kits) of primary human AML cells from 20 specimens of the Leucegene cohort enriched in intermediate and adverse genetic backgrounds ( KMT2A-rearranged n=5, chromosome 5 and/or 7 deletions (abn5/7, n=5) complex karyotype (n=4), NPM1/DNMT3A/FLT3-ITD triple-mutant (n=3) and others (n=3)). A Random Forest classifier was developed to unbiasedly classify AML cells into distinct differentiation stages using normal bone marrow-derived scRNA-seq data from the Human Cell Atlas (HCA) consortium. Genes were scored based on their probability of coding for proteins expressed at the cell surface using the SPAT algorithm developed by our group (https://doi.org/10.1101/2023.07.07.547075), retaining high score ones. To validate surface expression, we concomitantly analyzed the surface proteome (hereafter named surfaceome) of 100 primary human AML samples from the Leucegene cohort, including all 20 samples profiled by scRNA-seq. Results: After quality control, we profiled and characterized 103 690 high quality cells (mean of 5185 cells/sample). We trained a Random Forest classifier to annotate cells in a two step process, first identifying plasma cells based on a restricted list of genes abundantly expressed in these cells and subsequently assigning the remaining cells to one of 33 cell types. We performed a five-fold cross validation of the model and subsequently determined the accuracy of our classifier to be 92% on the test subset of the HCA data. Applied to our AML cell collection, a total of 35 053 cells (34%) were unbiasedly classified as Hematopoietic Stem Cell (HSC)-like, corresponding to the most phenotypically immature leukemic cells in each patient sample (ranging from 4 to 74 %). Accordingly, HSC-like AML cells preferentially express genes associated with normal HSCs, such as CD34, FAM30A, and SPINK2, and globally lack expression of mature lineages defining genes, further validating our classifier. The proportion of HSC-like cells varied among AML subgroups, and was lowest in KMT2A-r AML (median 19%) and highest in abn5/7 samples (46%). Integration of our AML atlas using Harmony algorithm preserved differentiation hierarchies across samples, with most cell types, including HSC-like cells, occupying a defined area in the low dimensional embedding. To identify new surface antigens specifically expressed in immature leukemic cells, we compared the high (≥8) SPAT score gene expression profile of AML HSC-like cells with that of normal HSC cells (HCA), and identified 60 genes significantly overexpressed in AML immature cells. Of those, 39 genes were also detected at the protein level by the surfaceome analysis, supporting their predicted expression at the cell surface in AML samples. 59% of these 39 genes (n=23) were detected in over 80% of the specimens analyzed by the surfaceome, and thus are nearly universally expressed in our AML cohort. To identify targets of therapies that could be repurposed, we next evaluated the relevance of our findings by querying the Thera-SAbDab database. Most interestingly, 8 of the 39 AML specific HSC markers are targeted by therapeutic antibodies FDA-approved or in clinical trials for the treatment of AML (n=4, IL3RA, FLT3, CD37 and TNFRSF10B) or other indications (n = 4). Conclusion Our genetically diverse AML single-cell atlas, supported by mass spectrometry, enables the identification of both subset-specific and pan-AML surface protein genes. These represent potential targets for antibody based strategy development or therapy repurposing in AML.
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
Piermaria Mendolicchio
Julia Pawar
Miruna Pȋslar
Alex Platonov
Evan Senter
Sukhdeep Singh
Alexander Zacherl
Lei M Zhang
Scalar Invariant Networks with Zero Bias
Chuqin Geng
Xiaojie Xu
Haolin Ye
Just like weights, bias terms are the learnable parameters of many popular machine learning models, including neural networks. Biases are th… (voir plus)ought to enhance the representational power of neural networks, enabling them to solve a variety of tasks in computer vision. However, we argue that biases can be disregarded for some image-related tasks such as image classification, by considering the intrinsic distribution of images in the input space and desired model properties from first principles. Our findings suggest that zero-bias neural networks can perform comparably to biased networks for practical image classification tasks. We demonstrate that zero-bias neural networks possess a valuable property called scalar (multiplication) invariance. This means that the prediction of the network remains unchanged when the contrast of the input image is altered. We extend scalar invariance to more general cases, enabling formal verification of certain convex regions of the input space. Additionally, we prove that zero-bias neural networks are fair in predicting the zero image. Unlike state-of-the-art models that may exhibit bias toward certain labels, zero-bias networks have uniform belief in all labels. We believe dropping bias terms can be considered as a geometric prior in designing neural network architecture for image classification, which shares the spirit of adapting convolutions as the transnational invariance prior. The robustness and fairness advantages of zero-bias neural networks may also indicate a promising path towards trustworthy and ethical AI.
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,… (voir plus) 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
Sonia Joseph
Kumar Krishna Agrawal
Arna Ghosh
On the Varied Faces of Overparameterization in Supervised and Self-Supervised Learning
Matteo Gamba
Arna Ghosh
Kumar Krishna Agrawal
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… (voir plus)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.
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