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Publications
scCross: A Deep Generative Model for Unifying Single-cell Multi-omics with Seamless Integration, Cross-modal Generation, and In-silico Exploration
Single-cell multi-omics illuminate intricate cellular states, yielding transformative insights into cellular dynamics and disease. Yet, whil… (voir plus)e the potential of this technology is vast, the integration of its multifaceted data presents challenges. Some modalities have not reached the robustness or clarity of established scRNA-seq. Coupled with data scarcity for newer modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross: a tool adeptly engineered using variational autoencoder, generative adversarial network principles, and the Mutual Nearest Neighbors (MNN) technique for modality alignment. This synergy ensures seamless integration of varied single-cell multi-omics data. Beyond its foundational prowess in multi-omics data integration, scCross excels in single-cell cross-modal data generation, multi-omics data simulation, and profound in-silico cellular perturbations. Armed with these capabilities, scCross is set to transform the field of single-cell research, establishing itself in the nuanced integration, generation, and simulation of complex multi-omics data.
Offline reinforcement learning has shown promise for solving tasks in safety-critical settings, such as clinical decision support. Its appli… (voir plus)cation, however, has been limited by the lack of interpretability and interactivity for clinicians. To address these challenges, we propose the medical decision transformer (MeDT), a novel and versatile framework based on the goal-conditioned reinforcement learning paradigm for sepsis treatment recommendation. MeDT uses the decision transformer architecture to learn a policy for drug dosage recommendation. During offline training, MeDT utilizes collected treatment trajectories to predict administered treatments for each time step, incorporating known treatment outcomes, target acuity scores, past treatment decisions, and current and past medical states. This analysis enables MeDT to capture complex dependencies among a patient's medical history, treatment decisions, outcomes, and short-term effects on stability. Our proposed conditioning uses acuity scores to address sparse reward issues and to facilitate clinician-model interactions, enhancing decision-making. Following training, MeDT can generate tailored treatment recommendations by conditioning on the desired positive outcome (survival) and user-specified short-term stability improvements. We carry out rigorous experiments on data from the MIMIC-III dataset and use off-policy evaluation to demonstrate that MeDT recommends interventions that outperform or are competitive with existing offline reinforcement learning methods while enabling a more interpretable, personalized and clinician-directed approach.
Reinforcement learning practitioners often avoid hierarchical policies, especially in image-based observation spaces. Typically, the single-… (voir plus)task performance improvement over flat-policy counterparts does not justify the additional complexity associated with implementing a hierarchy. However, by introducing multiple decision-making levels, hierarchical policies can compose lower-level policies to more effectively generalize between tasks, highlighting the need for multi-task evaluations. We analyze the benefits of hierarchy through simulated multi-task robotic control experiments from pixels. Our results show that hierarchical policies trained with task conditioning can (1) increase performance on training tasks, (2) lead to improved reward and state-space generalizations in similar tasks, and (3) decrease the complexity of fine tuning required to solve novel tasks. Thus, we believe that hierarchical policies should be considered when building reinforcement learning architectures capable of generalizing between tasks.
SETTING
Mathematical modelling played an important role in the public health response to COVID-19 in Canada. Variability in epidemic traject… (voir plus)ories, modelling approaches, and data infrastructure across provinces provides a unique opportunity to understand the factors that shaped modelling strategies.
INTERVENTION
Provinces implemented stringent pandemic interventions to mitigate SARS-CoV-2 transmission, considering evidence from epidemic models. This study aimed to summarize provincial COVID-19 modelling efforts. We identified modelling teams working with provincial decision-makers, through referrals and membership in Canadian modelling networks. Information on models, data sources, and knowledge translation were abstracted using standardized instruments.
OUTCOMES
We obtained information from six provinces. For provinces with sustained community transmission, initial modelling efforts focused on projecting epidemic trajectories and healthcare demands, and evaluating impacts of proposed interventions. In provinces with low community transmission, models emphasized quantifying importation risks. Most of the models were compartmental and deterministic, with projection horizons of a few weeks. Models were updated regularly or replaced by new ones, adapting to changing local epidemic dynamics, pathogen characteristics, vaccines, and requests from public health. Surveillance datasets for cases, hospitalizations and deaths, and serological studies were the main data sources for model calibration. Access to data for modelling and the structure for knowledge translation differed markedly between provinces.
IMPLICATION
Provincial modelling efforts during the COVID-19 pandemic were tailored to local contexts and modulated by available resources. Strengthening Canadian modelling capacity, developing and sustaining collaborations between modellers and governments, and ensuring earlier access to linked and timely surveillance data could help improve pandemic preparedness.
Language models exhibit scaling laws, whereby increasing model and dataset size yields predictable decreases in negative log likelihood, unl… (voir plus)ocking a dazzling array of capabilities. This phenomenon spurs many companies to train ever larger models in pursuit of ever improved performance. Yet, these models are vulnerable to adversarial inputs such as ``jailbreaks'' and prompt injections that induce models to perform undesired behaviors, posing a growing risk as models become more capable. Prior work indicates that computer vision models become more robust with model and data scaling, raising the question: does language model robustness also improve with scale? We study this question empirically in the classification setting, finding that without explicit defense training, larger models tend to be modestly more robust on most tasks, though the effect is not reliable. Even with the advantage conferred by scale, undefended models remain easy to attack in absolute terms, and we thus turn our attention to explicitly training models for adversarial robustness, which we show to be a much more compute-efficient defense than scaling model size alone. In this setting, we also observe that adversarially trained larger models generalize faster and better to modified attacks not seen during training when compared with smaller models. Finally, we analyze the offense/defense balance of increasing compute, finding parity in some settings and an advantage for offense in others, suggesting that adversarial training alone is not sufficient to solve robustness, even at greater model scales.
Approximately two-thirds of survivors of childhood acute lymphoblastic leukemia (ALL) cancer develop late adverse effects post-treatment. Pr… (voir plus)ior studies explored prediction models for personalized follow-up, but none integrated the usage of neural networks to date. In this work, we propose the Error Passing Network (EPN), a graph-based method that leverages relationships between samples to propagate residuals and adjust predictions of any machine learning model. We tested our approach to estimate patients’ \vo peak, a reliable indicator of their cardiac health. We used the EPN in conjunction with several baseline models and observed up to 12.16% improvement in the mean average percentage error compared to the last established equation predicting \vo peak in childhood ALL survivors. Along with this performance improvement, our final model is more efficient considering that it relies only on clinical variables that can be self-reported by patients, therefore removing the previous need of executing a resource-consuming physical test.
2024-07-24
Proceedings of the fifth Conference on Health, Inference, and Learning (publié)
Spinal cord injury (SCI) is a devastating incidence leading to permanent paralysis and loss of sensory-motor functions potentially resulting… (voir plus) in the formation of lesions within the spinal cord. Imaging biomarkers obtained from magnetic resonance imaging (MRI) scans can predict the functional recovery of individuals with SCI and help choose the optimal treatment strategy. Currently, most studies employ manual quantification of these MRI-derived biomarkers, which is a subjective and tedious task. In this work, we propose (i) a universal tool for the automatic segmentation of intramedullary SCI lesions, dubbed \texttt{SCIsegV2}, and (ii) a method to automatically compute the width of the tissue bridges from the segmented lesion. Tissue bridges represent the spared spinal tissue adjacent to the lesion, which is associated with functional recovery in SCI patients. The tool was trained and validated on a heterogeneous dataset from 7 sites comprising patients from different SCI phases (acute, sub-acute, and chronic) and etiologies (traumatic SCI, ischemic SCI, and degenerative cervical myelopathy). Tissue bridges quantified automatically did not significantly differ from those computed manually, suggesting that the proposed automatic tool can be used to derive relevant MRI biomarkers. \texttt{SCIsegV2} and the automatic tissue bridges computation are open-source and available in Spinal Cord Toolbox (v6.4 and above) via the \texttt{sct\_deepseg -task seg\_sc\_lesion\_t2w\_sci} and \texttt{sct\_analyze\_lesion} functions, respectively.
Recent advancements in massively multilingual machine translation systems have significantly enhanced translation accuracy; however, even th… (voir plus)e best performing systems still generate hallucinations, severely impacting user trust. Detecting hallucinations in Machine Translation (MT) remains a critical challenge, particularly since existing methods excel with High-Resource Languages (HRLs) but exhibit substantial limitations when applied to Low-Resource Languages (LRLs). This paper evaluates sentence-level hallucination detection approaches using Large Language Models (LLMs) and semantic similarity within massively multilingual embeddings. Our study spans 16 language directions, covering HRLs, LRLs, with diverse scripts. We find that the choice of model is essential for performance. On average, for HRLs, Llama3-70B outperforms the previous state of the art by as much as 0.16 MCC (Matthews Correlation Coefficient). However, for LRLs we observe that Claude Sonnet outperforms other LLMs on average by 0.03 MCC. The key takeaway from our study is that LLMs can achieve performance comparable or even better than previously proposed models, despite not being explicitly trained for any machine translation task. However, their advantage is less significant for LRLs.
We present the first application of data-driven techniques for dynamical system analysis based on Koopman theory to variable stars. We focus… (voir plus) on light curves of RRLyrae type variables, in the Galactic globular cluster
