Publications

TCR/Chimeric Antigen Receptor (CAR) Cross-Antagonism to Fine-Tune CAR-T cell Immunotherapy
Grégoire Altan-Bonnet
Taisuke Kondo
François X. P. Bourassa
Sooraj R. Achar
Justyn DuSold
Pablo Cespedes
Madison Wahlsten
Guillaume Gaud
Paul E Love
Mike Dustin
Paul François
Naomi Taylor
Chimeric antigen receptor (CAR) T cells, are created by extracting T cells from a cancer patient, engineering them to express a CAR targetin… (see more)g a tumor specific molecule, then reintroducing them back into the patient. A patient’s T cells contain their own endogenous T cell receptors (TCRs) however, which could potentially interact with the exogenous CAR inserted into the cell. In this study, we examine how TCR and CAR signals interact upon CAR-T activation. We show that weak TCR stimulation can reduce (antagonize) or increase overall CAR-T response, both in vitro and in vivo, across multiple tumor models, in both mouse and human T cells. We further show that the behavior of these TCR/CAR interactions can be manipulated by changing various characteristics of the TCR, CAR, and associated ligands. While this behavior is complex, we show that it can be described by a single mathematical model based on the adaptive kinetic proofreading scheme of ligand discrimination. We conclude by presenting potential applications for cancer immunotherapy. Intramural Research Program of the National Cancer Institute
2023-04-30
Journal of Immunology (published)
doi.org
The study of plasticity has always been about gradients
Blake Aaron Richards
Konrad Paul Kording
2023-04-30
The Journal of Physiology (published)
doi.org
UnityLint: A Bad Smell Detector for Unity
Matteo Bosco
Pasquale Cavoto
Augusto Ungolo
Biruk Asmare Muse
Foutse Khomh
Vittoria Nardone
Massimiliano Di Penta
The video game industry is particularly rewarding as it represents a large portion of the software development market. However, working in t… (see more)his domain may be challenging for developers, not only because of the need for heterogeneous skills (from software design to computer graphics), but also for the limited body of knowledge in terms of good and bad design and development principles, and the lack of tool support to assist them. This tool demo proposes UnityLint, a tool able to detect 18 types of bad smells in Unity video games. UnityLint builds upon a previously-defined and validated catalog of bad smells for video games. The tool, developed in C# and available both as open-source and binary releases, is composed of (i) analyzers that extract facts from video game source code and metadata, and (ii) smell detectors that leverage detection rules to identify smells on top of the extracted facts.Tool: https://github.com/mdipenta/UnityCodeSmellAnalyzerTeaser Video: https://youtu.be/HooegxZ8H6g
2023-04-30
IEEE International Conference on Program Comprehension (published)
doi.org
What did the T cell see? A deep-learning model of CD8+ T cell activation reveals sharp antigen discrimination at the single cell level
Madison Wahlsten
Amin Akhshi
Sooraj R. Achar
Anagha Yogam Krishnan
Paul François
Grégoire Altan-Bonnet
Immunotherapies such as checkpoint blockade antibodies to block T cell exhaustion have been successful in several cancers such as non-small … (see more)cell lung cancer and melanoma, but limited in others (e.g., pancreatic or prostate carcinomas) owing to differences in tumor antigenicity. Therefore, quantifying tumor antigenicity is critical for successful immunotherapies. Our lab has shown that antigenicity can be encoded in a single parameter derived from bulk cytokine dynamics in ex vivo co-cultures between antigen presenting cells (APCs) and T cells. Here we built a model that can capture the antigenicity seen by individual cells. Using a custom robotic platform, we generated high-throughput kinetics of T cell activation in co-culture with APCs by analyzing cells at various timepoints across a large set of activation conditions. We performed spectral flow cytometry to measure the expression of up to 30 surface markers and intracellular signals per cell. To analyze our content-rich datasets, we designed a machine learning-based model that can classify the antigen seen by an individual cell using expression values from flow cytometry. The model performs well not only at classifying T cells (ROC-AUC > 0.91), but also APCs (ROC-AUC > 0.88), suggesting that each individual leukocyte may register the quality of antigen being presented. Blocking cytokine signaling disrupted this antigen classification. Our study demonstrates that every individual lymphocyte can bridge local and global response to achieve high discriminatory power of antigens.
2023-04-30
Journal of Immunology (published)
doi.org
Estimating individual minimum calibration for deep-learning with predictive performance recovery: An example case of gait surface classification from wearable sensor gait data
Guillaume Lam
Irina Rish
Philippe C. Dixon
2023-04-29
Journal of Biomechanics (unknown)
doi.org
Can ChatGPT Pass An Introductory Level Functional Language Programming Course?
Chuqin Geng
Yihan Zhang
Brigitte Pientka
Xujie Si
The recent introduction of ChatGPT has drawn significant attention from both industry and academia due to its impressive capabilities in sol… (see more)ving a diverse range of tasks, including language translation, text summarization, and computer programming. Its capability for writing, modifying, and even correcting code together with its ease of use and access is already dramatically impacting computer science education. This paper aims to explore how well ChatGPT can perform in an introductory-level functional language programming course. In our systematic evaluation, we treated ChatGPT as one of our students and demonstrated that it can achieve a grade B- and its rank in the class is 155 out of 314 students overall. Our comprehensive evaluation provides valuable insights into ChatGPT's impact from both student and instructor perspectives. Additionally, we identify several potential benefits that ChatGPT can offer to both groups. Overall, we believe that this study significantly clarifies and advances our understanding of ChatGPT's capabilities and potential impact on computer science education.
2023-04-28
ArXiv (preprint)
doi.org
arxiv.org
Leveraging Data Mining Algorithms to Recommend Source Code Changes
AmirHossein Naghshzan
Saeed Khalilazar
Pierre Poilane
Olga Baysal
Latifa Guerrouj
Foutse Khomh
2023-04-28
ArXiv (preprint)
doi.org
arxiv.org
Group Fairness in Reinforcement Learning
Harsh Satija
Alessandro Lazaric
Matteo Pirotta
Joelle Pineau
We pose and study the problem of satisfying fairness in the online Reinforcement Learning (RL) setting. We focus on the group notions of fai… (see more)rness, according to which agents belonging to different groups should have similar performance based on some given measure. We consider the setting of maximizing return in an unknown environment (unknown transition and reward function) and show that it is possible to have RL algorithms that learn the best fair policies without violating the fairness requirements at any point in time during the learning process. In the tabular finite-horizon episodic setting, we provide an algorithm that combines the principle of optimism and pessimism under uncertainty to achieve zero fairness violation with arbitrarily high probability while also maintaining sub-linear regret guarantees. For the high-dimensional Deep-RL setting, we present algorithms based on the performance-difference style approximate policy improvement update step and we report encouraging empirical results on various traditional RL-inspired benchmarks showing that our algorithms display the desired behavior of learning the optimal policy while performing a fair learning process.
2023-04-27
TMLR (accepted)
openreview.net
openreview.net
Overcoming Interpretability and Accuracy Trade-off in Medical Imaging
Ivaxi Sheth
S Ebrahimi Kahou
2023-04-27
MIDL.io/2023/Short_Paper_Track (poster)
openreview.net
openreview.net
Use of Invasive Brain-Computer Interfaces in Pediatric Neurosurgery: Technical and Ethical Considerations
David Bergeron
Christian Iorio-Morin
Marco Bonizzato
Guillaume Lajoie
Nathalie Orr Gaucher
Éric Racine
Alexander G. Weil
2023-04-27
Journal of Child Neurology (published)
doi.org
Lightweight, Pre-trained Transformers for Remote Sensing Timeseries
Gabriel Tseng
Ivan Zvonkov
Ruben Cartuyvels
Mirali Purohit
David Rolnick
Hannah Kerner
Machine learning methods for satellite data have a range of societally relevant applications, but labels used to train models can be difficu… (see more)lt or impossible to acquire. Self-supervision is a natural solution in settings with limited labeled data, but current self-supervised models for satellite data fail to take advantage of the characteristics of that data, including the temporal dimension (which is critical for many applications, such as monitoring crop growth) and availability of data from many complementary sensors (which can significantly improve a model's predictive performance). We present Presto (the Pretrained Remote Sensing Transformer), a model pre-trained on remote sensing pixel-timeseries data. By designing Presto specifically for remote sensing data, we can create a significantly smaller but performant model. Presto excels at a wide variety of globally distributed remote sensing tasks and performs competitively with much larger models while requiring far less compute. Presto can be used for transfer learning or as a feature extractor for simple models, enabling efficient deployment at scale.
2023-04-26
ArXiv (preprint)
doi.org
openreview.net
The Influence of Age, Sex, and Socioeconomic Status on Glycemic Control Among People With Type 1 and Type 2 Diabetes in Canada: Patient-Led Longitudinal Retrospective Cross-sectional Study With Multiple Time Points of Measurement
Seyedmostafa Mousavi
Dana Tannenbaum Greenberg
Ruth Ndjaboué
Michelle Greiver
Olivia Drescher
Selma Chipenda Dansokho
Denis Boutin
Jean-Marc Chouinard
Sylvie Dostie
Robert Fenton
Marley Greenberg
Jonathan McGavock
Adhiyat Najam
Monia Rekik
Tom Weisz
Donald J Willison
Audrey Durand
Holly O Witteman
2023-04-26
JMIR Diabetes (published)
doi.org