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Publications
Bugs in machine learning-based systems: a faultload benchmark
Abstract 2987: BamQuery: a new proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens
Maria-Virginia Ruiz Cuevas
Marie-Pierre Hardy
Jean-David Larouche
Anca Apavaloaei
Eralda Kina
Krystel Vincent
Patrick Gendron
Jean-Philippe Laverdure
Chantal Durette
Pierre Thibault
S. Lemieux
Claude Perreault
Gregory Ehx
MHC class I-associated peptides (MAPs), collectively referred to as the immunopeptidome, have a pivotal role in cancer immunosurveillance. W… (voir plus)hile MAPs were long thought to be solely generated by the degradation of canonical proteins, recent advances in the field of proteogenomics (genomically-informed proteomics) evidenced that ∼10% of them originate from allegedly noncoding genomic sequences. Among these sequences, endogenous retroelements (EREs) are under intense scrutiny as a possible source of actionable tumor antigens (TAs). With the increasing number of cancer-oriented immunopeptidomic and proteogenomic studies comes the need to accurately attribute an RNA expression level to each MAP identified by mass-spectrometry. Here, we introduce BamQuery (BQ), a computational tool to attribute an exhaustive RNA expression to MAPs of any genomic origin (exon, intron, UTR, intergenic) from bulk and single-cell RNA-sequencing data. By using BQ on large datasets of published MAPs identified by mass spectrometry, we show that many of them can arise from more than one genomic region. Indeed, 27% of MAPs reported as deriving from protein-coding exons (canonical MAPs) could also arise from non-canonical genomic regions, sometimes with greater probability, and 61% of non-canonical MAPs could arise from more than a single genomic origin (334 possible regions on average per non-canonical MAP; up to 35,343 for EREs). The consideration of all these origins evidenced an unsuspected high RNA expression in normal human tissues of (i) published neoantigens/TAs (mutated or not); (ii) MAPs derived from proteasomal splicing, supposedly not genomically templated, and (iii) MAPs derived from viruses. In particular, the high expression of candidate immunotherapeutic targets such as TAs highlights the relevance of BamQuery and the necessity of using it to validate such antigens before translating their usage in clinical trials. We also demonstrate that BamQuery can be used to directly identify safe and actionable TAs as well as to predict their immunogenicity through our freely accessible web portal (https://bamquery.iric.ca/search). Therefore, BQ could become an essential tool in any TA prioritization pipeline in the near future.
Citation Format: Maria-Virginia Ruiz Cuevas, Marie-Pierre Hardy, Jean-David Larouche, Anca Apavaloaei, Eralda Kina, Krystel Vincent, Patrick Gendron, Jean-Philippe Laverdure, Chantal Durette, Pierre Thibault, Sebastien Lemieux, Claude Perreault, Gregory Ehx. BamQuery: a new proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2987.
Abstract 2993: Unmutated tumor antigens are abundant and contribute to tumor control in melanoma
Anca Apavaloaei
Qingchuan Zhao
Leslie Hesnard
Krystel Vincent
Marie-Pierre Hardy
Chantal Durette
Joël Lanoix
Jean-Philippe Laverdure
Jean-David Larouche
Maria-Virginia Ruiz Cuevas
Gregory Ehx
S. Lemieux
Pierre Thibault
Claude Perreault
Recognition of MHC-I-associated tumor antigens (TAs) by CD8+ T cells is central to antitumor immunity. Owing to the elevated tumor mutationa… (voir plus)l burden (TMB) in melanoma, the marked efficacy of immune checkpoint blockade (ICB) has been attributed to the recognition of mutated TAs. However, recent reports showed that response to ICB in melanomas with low TMB is associated with CD8+ T-cell reactivity against melanocyte lineage-associated antigens (LSAs). Here, we systematically evaluated the contribution of all TA classes, i.e., mutated and unmutated, canonical and non-canonical, to the antigenic landscape of melanoma. We characterized the TAs from melanoma biopsies and patient-derived cell lines using proteogenomics. Out of 79450 MHC-I-associated peptides (MAPs) identified from 19 samples, we found 557 unmutated TAs classified as tumor-specific (TSA), tumor-associated (TAA), or LSAs. These TAs most often derived from annotated open-reading frames, followed by ncRNAs and intergenic regions. By contrast, only 6 MAPs were mutated and tumor-specific, which could be partially explained by a decreased expression of mutations within MAP-generating genomic regions. While the number of unmutated TAs with predicted presentation (TApres) in melanoma patients was similar between responders and non-responders pre-ICB, non-responders showed marks of inefficient antigen presentation. In consequence, only responders lost TApres upon treatment, in tandem with an expansion in tumor-infiltrating lymphocytes. These results reveal a previously underappreciated contribution of unmutated TAs to tumor control in melanoma and suggest that enhancing their recognition could improve the ICB efficacy in non-responders.
Citation Format: Anca Apavaloaei, Qingchuan Zhao, Leslie Hesnard, Krystel Vincent, Marie-Pierre Hardy, Chantal Durette, Joël Lanoix, Jean-Philippe Laverdure, Jean-David Larouche, Maria Virginia Ruiz Cuevas, Grégory Ehx, Sébastien Lemieux, Pierre Thibault, Claude Perreault. Unmutated tumor antigens are abundant and contribute to tumor control in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2993.
To offer accurate and diverse recommendation services, recent methods use auxiliary information to foster the learning process of user and i… (voir plus)tem representations. Many state-of-the-art (SOTA) methods fuse different sources of information (user, item, knowledge graph, tags, etc.) into a graph and use Graph Neural Networks (GNNs) to introduce the auxiliary information through the message passing paradigm. In this work, we seek an alternative framework that is light and effective through self-supervised learning across different sources of information, particularly for the commonly accessible item tag information. We use a self-supervision signal to pair users with the auxiliary information (tags) associated with the items they have interacted with before. To achieve the pairing, we create a proxy training task. For a given item, the model predicts which is the correct pairing between the representations obtained from the users that have interacted with this item and the tags assigned to it. This design provides an efficient solution, using the auxiliary information directly to enhance the quality of user and item embeddings. User behavior in recommendation systems is driven by the complex interactions of many factors behind the users’ decision-making processes. To make the pairing process more fine-grained and avoid embedding collapse, we propose a user intent-aware self-supervised pairing process where we split the user embeddings into multiple sub-embedding vectors. Each sub-embedding vector captures a specific user intent via self-supervised alignment with a particular cluster of tags. We integrate our designed framework with various recommendation models, demonstrating its flexibility and compatibility. Through comparison with numerous SOTA methods on seven real-world datasets, we show that our method can achieve better performance while requiring less training time. This indicates the potential of applying our approach on web-scale datasets.
2023-04-02
2023 IEEE 39th International Conference on Data Engineering (ICDE) (publié)
Objective While National Surgical, Obstetric and Anaesthesia Plans (NSOAPs) have emerged as a strategy to strengthen and scale up surgical h… (voir plus)ealthcare systems in low/middle-income countries (LMICs), the degree to which children’s surgery is addressed is not well-known. This study aims to assess the inclusion of children’s surgical care among existing NSOAPs, identify practice examples and provide recommendations to guide inclusion of children’s surgical care in future policies. Design We performed two qualitative content analyses to assess the inclusion of children’s surgical care among NSOAPs. We applied a conventional (inductive) content analysis approach to identify themes and patterns, and developed a framework based on the Global Initiative for Children’s Surgery’s Optimal Resources for Children’s Surgery document. We then used this framework to conduct a directed (deductive) content analysis of the NSOAPs of Ethiopia, Nigeria, Rwanda, Senegal, Tanzania and Zambia. Results Our framework for the inclusion of children’s surgical care in NSOAPs included seven domains. We evaluated six NSOAPs with all addressing at least two of the domains. All six NSOAPs addressed ‘human resources and training’ and ‘infrastructure’, four addressed ‘service delivery’, three addressed ‘governance and financing’, two included ‘research, evaluation and quality improvement’, and one NSOAP addressed ‘equipment and supplies’ and ‘advocacy and awareness’. Conclusions Additional focus must be placed on the development of surgical healthcare systems for children in LMICs. This requires a focus on children’s surgical care separate from adult surgical care in the scaling up of surgical healthcare systems, including children-focused needs assessments and the inclusion of children’s surgery providers in the process. This study proposes a framework for evaluating NSOAPs, highlights practice examples and suggests recommendations for the development of future policies.
Neural stimulation can alleviate paralysis and sensory deficits. Novel high-density neural interfaces can enable refined and multipronged ne… (voir plus)urostimulation interventions. To achieve this, it is essential to develop algorithmic frameworks capable of handling optimization in large parameter spaces. Here, we leveraged an algorithmic class, Gaussian-process (GP)-based Bayesian optimization (BO), to solve this problem. We show that GP-BO efficiently explores the neurostimulation space, outperforming other search strategies after testing only a fraction of the possible combinations. Through a series of real-time multi-dimensional neurostimulation experiments, we demonstrate optimization across diverse biological targets (brain, spinal cord), animal models (rats, non-human primates), in healthy subjects, and in neuroprosthetic intervention after injury, for both immediate and continual learning over multiple sessions. GP-BO can embed and improve “prior” expert/clinical knowledge to dramatically enhance its performance. These results advocate for broader establishment of learning agents as structural elements of neuroprosthetic design, enabling personalization and maximization of therapeutic effectiveness.
Summary The massive and continuously increasing volume of biomedical knowledge derived from biological experiments or gained from healthcare… (voir plus) practices has become an invaluable treasure for biomedicine. The emerging biomedical knowledge graphs (BKGs) provide an efficient and effective way to manage the abundant knowledge in biomedical and life science. In the present study, we harmonized and integrated data from diverse biomedical resources to curate a comprehensive BKG, named the integrative Biomedical Knowledge Hub (iBKH). To facilitate the usage of iBKH in biomedical research, we developed a web-based, easy-to-use, publicly available graphical portal that allows fast, interactive, and visualized knowledge retrieval in iBKH. Furthermore, an efficient and scalable graph learning pipeline was developed for novel knowledge discovery in iBKH. As a proof of concept, we performed our iBKH-based method for computational in silico drug repurposing for Alzheimer’s disease. The iBKH is publicly available at: http://ibkh.ai/ .
Machine-learning-based arc selection for constrained shortest path problems in column generation
Mouad Morabit
Guy Desaulniers
Andrea Lodi
Column generation is an iterative method used to solve a variety of optimization problems. It decomposes the problem into two parts: a maste… (voir plus)r problem and one or more pricing problems (PP). The total computing time taken by the method is divided between these two parts. In routing or scheduling applications, the problems are mostly defined on a network, and the PP is usually an NP-hard shortest path problem with resource constraints. In this work, we propose a new heuristic pricing algorithm based on machine learning. By taking advantage of the data collected during previous executions, the objective is to reduce the size of the network and accelerate the PP, keeping only the arcs that have a high chance to be part of the linear relaxation solution. The method has been applied to two specific problems: the vehicle and crew scheduling problem in public transit and the vehicle routing problem with time windows. Reductions in computational time of up to 40% can be obtained.