Publications

Coordination among leaf and fine root traits across a strong natural soil fertility gradient
Xavier Guilbeault-Mayers
Hans Lambers
Étienne Laliberté
2023-11-04
bioRxiv (preprint)
doi.org
Player-Guided AI outperforms standard AI in Sequence Alignment Puzzles.
Renata Mutalova
Roman Sarrazin-Gendron
Parham Ghasemloo Gheidari
Eddie Cai
Gabriel Richard
Sébastien Caisse
Rob Knight
Mathieu Blanchette
Attila Szantner
Jérôme Waldispühl
Although Artificial Intelligence (AI) has gained widespread popularity across different fields, it is essential to recognize that AI systems… (see more), while impressive, do not consistently exhibit robust generalization, particularly for difficult problems such as the Multiple Sequence Alignment (MSA). In this study, we focus on bridging this performance gap by integrating human solutions into AI training. To illustrate these principles, we leverage data from Borderlands Science, a popular citizen science game in which small instances of the MSA problem are represented as puzzles. Our goal is to leverage the collective intelligence of human players to enhance the capabilities of AI agents. To achieve this, we have developed a Player-guided AI system that enables the AI model to learn from both standard training processes and the solutions provided by players. Our findings demonstrate that incorporating human-annotated information into the AI model improves its performance on puzzle tasks. Furthermore, the Player-guided AI model shows a decrease in noise compared to a pure AI model. This advancement allows for leveraging the model to align new sequences with improved accuracy and effectiveness. Moreover, this research brings attention to the potential of integrating AI and human expertise to address other challenges where the performance of AI models may be unsatisfactory.
2023-11-04
International Conference on Climate Informatics (published)
doi.org
The feature landscape of visual cortex
Rudi Tong
Ronan da Silva
Dongyan Lin
Arna Ghosh
James Wilsenach
Erica Cianfarano
Pouya Bashivan
Blake Richards
Stuart Trenholm
Understanding computations in the visual system requires a characterization of the distinct feature preferences of neurons in different visu… (see more)al cortical areas. However, we know little about how feature preferences of neurons within a given area relate to that area’s role within the global organization of visual cortex. To address this, we recorded from thousands of neurons across six visual cortical areas in mouse and leveraged generative AI methods combined with closed-loop neuronal recordings to identify each neuron’s visual feature preference. First, we discovered that the mouse’s visual system is globally organized to encode features in a manner invariant to the types of image transformations induced by self-motion. Second, we found differences in the visual feature preferences of each area and that these differences generalized across animals. Finally, we observed that a given area’s collection of preferred stimuli (‘own-stimuli’) drive neurons from the same area more effectively through their dynamic range compared to preferred stimuli from other areas (‘other-stimuli’). As a result, feature preferences of neurons within an area are organized to maximally encode differences among own-stimuli while remaining insensitive to differences among other-stimuli. These results reveal how visual areas work together to efficiently encode information about the external world.
2023-11-04
bioRxiv (preprint)
doi.org
Score-Based Likelihood Characterization for Inverse Problems in the Presence of Non-Gaussian Noise
Ronan Legin
Alexandre Adam
Yashar Hezaveh
Laurence Perreault-Levasseur
Likelihood analysis is typically limited to normally distributed noise due to the difficulty of determining the probability density function… (see more) of complex, high-dimensional, non-Gaussian, and anisotropic noise. This work presents Score-based LIkelihood Characterization (SLIC), a framework that resolves this issue by building a data-driven noise model using a set of noise realizations from observations. We show that the approach produces unbiased and precise likelihoods even in the presence of highly non-Gaussian correlated and spatially varying noise. We use diffusion generative models to estimate the gradient of the probability density of noise with respect to data elements. In combination with the Jacobian of the physical model of the signal, we use Langevin sampling to produce independent samples from the unbiased likelihood. We demonstrate the effectiveness of the method using real data from the Hubble Space Telescope and James Webb Space Telescope.
2023-11-02
NeurIPS.cc/2023/Workshop/Deep_Inverse (poster)
openreview.net
openreview.net
Transposable elements regulate thymus development and function
Jean-David Larouche
Céline M Laumont
Assya Trofimov
Krystel Vincent
Leslie Hesnard
Sylvie Brochu
Caroline Coté
Juliette F Humeau
Éric Bonneil
Joël Lanoix
Chantal Durette
Patrick Gendron
Jean-Philippe Laverdure
Ellen R Richie
Sébastien Lemieux
Pierre Thibault
Claude Perreault
Abstract Transposable elements (TE) are repetitive sequences representing ∼45% of the human and mouse genomes and are high… (see more)ly expressed by medullary thymic epithelial cells (mTEC). In this study, we investigated the role of transposable elements (TE), which are highly expressed by medullary thymic epithelial cells (mTEC), on T-cell development in the thymus. We performed multi-omic analyses of TEs in human and mouse thymic cells to elucidate their role in T cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TEs interact with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDC). In mTECs, TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and RELB) and generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that lead to the formation of dsRNA, triggering RIG-I and MDA5 signaling and explaining why thymic pDCs constitutively secrete IFN ɑ/β. This study illustrates the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that the orchestration of TE expression in thymic cells is critical to prevent autoimmunity in vertebrates.
2023-11-02
eLife (published)
doi.org
Goal Misgeneralization as Implicit Goal Conditioning
Diego Dorn
Neel Alex
David M. Krueger
2023-11-01
NeurIPS.cc/2023/Workshop/GCRL (published)
openreview.net
openreview.net
How does fine-tuning affect your model? Mechanistic analysis on procedural tasks
Samyak Jain
Robert Kirk
Ekdeep Singh Lubana
Robert P. Dick
Hidenori Tanaka
Tim Rocktäschel
Edward Grefenstette
David M. Krueger
Fine-tuning large pre-trained models has become the *de facto* strategy for developing models that are safe to deploy. However, there has be… (see more)en little work that explains how fine-tuning alters the underlying capabilities learnt by a model during pretraining: does fine-tuning yield entirely novel capabilities or does it just modulate existing ones? We address this question empirically in *synthetic* settings with mechanistic interpretability tools (e.g., network pruning and probing) to understand how the model's underlying capabilities are changing. Our extensive analysis of the effects of fine-tuning shows: (i) fine-tuning rarely alters the underlying model capabilities; (ii) a minimal transformation, which we call a 'wrapper', is typically learned on top of the underlying model capabilities; and (iii) further fine-tuning on a task where such wrapped capabilities are relevant leads to sample-efficient "revival'' of the capability, i.e., the model begins reusing this capability in a few gradient steps. *This indicates practitioners can unintentionally remove a model's safety wrapper by merely fine-tuning it on a superficially unrelated task.* We additionally perform analysis on language models trained on the TinyStories dataset to support our claims in a more realistic setup.
2023-11-01
NeurIPS.cc/2023/Workshop/UniReps (poster)
openreview.net
openreview.net
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-François Spinella
Jalila Chagraoui
Ossama Moujaber
Laure Mallinger
Isabel Boivin
Nadine Mayotte
Azadeh Hajmirza
Éric Bonneil
Francois Beliveau
Albert Feghali
Geneviève Boucher
Patrick Gendron
Frederic Barabe … (see 6 more)
Sébastien Lemieux
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. Desp… (see more)ite breakthroughs 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.
2023-11-01
Blood (published)
doi.org
Pepid: a Highly Modifiable, Bioinformatics-Oriented Peptide Search Engine
Jeremie Zumer
S. Lemieux
2023-11-01
bioRxiv (preprint)
doi.org
Electric Power Fuse Identification With Deep Learning
Simon Giard-Leroux
Guillaume Cléroux
Shreyas Sunil Kulkarni
François Bouffard
Martin Vallières
As part of arc flash studies, survey pictures of electrical installations need to be manually analyzed. A challenging task is to identify fu… (see more)se types, which can be determined from physical characteristics, such as shape, color, and size. To automate this process using deep learning techniques, a new dataset of fuse pictures from past arc flash projects and data from the web was created. Multiple experiments were performed to train a final model, reaching an average precision of 91.06% on the holdout set, which confirms its potential for identification of fuse types in new photos. By identifying fuse types using physical characteristics only, the need to take clear pictures of the label text is eliminated, allowing pictures to be taken away from danger, thereby improving the safety of workers. All the resources needed to repeat the experiments are openly accessible, including the code and datasets.
2023-10-31
IEEE Transactions on Industrial Informatics (published)
doi.org
Integrating Equity, Diversity, and Inclusion Throughout the Lifecycle of Artificial Intelligence for Better Health and Oral Health Care: A Workshop Summary.
Elham Emami
S. A. Rahimi
Milka Nyariro
Professors Elham Emami and Samira Rahimi organized and co-led an international interdisciplinary workshop in June 2023 at McGill University,… (see more) built upon an intersectoral approach addressing equity, diversity and inclusion within the field of AI.
2023-10-31
Journal (published)
pubmed.ncbi.nlm.nih.gov
Invasive Brain Computer Interface for Motor Restoration in Spinal Cord Injury: A Systematic Review.
Jordan J. Levett
Lior M. Elkaim
Farbod Niazi
Michael H. Weber
Christian Iorio-Morin
Marco Bonizzato
Alexander G. Weil
2023-10-31
Neuromodulation: Technology at the Neural Interface (published)
doi.org