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Publications
A novel and efficient machine learning Mendelian randomization estimator applied to predict the safety and efficacy of sclerostin inhibition
Mendelian Randomization (MR) enables estimation of causal effects while controlling for unmeasured confounding factors. However, traditional… (see more) MR's reliance on strong parametric assumptions can introduce bias if these are violated. We introduce a new machine learning MR estimator named Quantile Instrumental Variable (IV) that achieves low estimation error in a wide range of plausible MR scenarios. Quantile IV is distinctive in its ability to estimate nonlinear and heterogeneous causal effects and offers a flexible approach for subgroup analysis. Applying Quantile IV, we investigate the impact of circulating sclerostin levels on heel bone mineral density, osteoporosis, and cardiovascular outcomes in the UK Biobank. Employing various MR estimators and colocalization techniques that allow multiple causal variants, our analysis reveals that a genetically predicted reduction in sclerostin levels significantly increases heel bone mineral density and reduces the risk of osteoporosis, while showing no discernible effect on ischemic cardiovascular diseases. Quantile IV contributes to the advancement of MR methodology, and the case study on the impact of circulating sclerostin modulation contributes to our understanding of the on-target effects of sclerostin inhibition.
Abstract Motivation Up to 75% of the human genome encodes RNAs. The function of many non-coding RNAs relies on their ability to fold into 3D… (see more) structures. Specifically, nucleotides inside secondary structure loops form non-canonical base pairs that help stabilize complex local 3D structures. These RNA 3D motifs can promote specific interactions with other molecules or serve as catalytic sites. Results We introduce PERFUMES, a computational pipeline to identify 3D motifs that can be associated with observable features. Given a set of RNA sequences with associated binary experimental measurements, PERFUMES searches for RNA 3D motifs using BayesPairing2 and extracts those that are over-represented in the set of positive sequences. It also conducts a thermodynamics analysis of the structural context that can support the interpretation of the predictions. We illustrate PERFUMES’ usage on the SNRPA protein binding site, for which the tool retrieved both previously known binder motifs and new ones. Availability and implementation PERFUMES is an open-source Python package (https://jwgitlab.cs.mcgill.ca/arnaud_chol/perfumes).
This paper presents a comprehensive study on using deep reinforcement learning (RL) to create dynamic locomotion controllers for bipedal rob… (see more)ots. Going beyond focusing on a single locomotion skill, we develop a general control solution that can be used for a range of dynamic bipedal skills, from periodic walking and running to aperiodic jumping and standing. Our RL-based controller incorporates a novel dual-history architecture, utilizing both a long-term and short-term input/output (I/O) history of the robot. This control architecture, when trained through the proposed end-to-end RL approach, consistently outperforms other methods across a diverse range of skills in both simulation and the real world.The study also delves into the adaptivity and robustness introduced by the proposed RL system in developing locomotion controllers. We demonstrate that the proposed architecture can adapt to both time-invariant dynamics shifts and time-variant changes, such as contact events, by effectively using the robot's I/O history. Additionally, we identify task randomization as another key source of robustness, fostering better task generalization and compliance to disturbances. The resulting control policies can be successfully deployed on Cassie, a torque-controlled human-sized bipedal robot. This work pushes the limits of agility for bipedal robots through extensive real-world experiments. We demonstrate a diverse range of locomotion skills, including: robust standing, versatile walking, fast running with a demonstration of a 400-meter dash, and a diverse set of jumping skills, such as standing long jumps and high jumps.
This paper presents a comprehensive study on using deep reinforcement learning (RL) to create dynamic locomotion controllers for bipedal rob… (see more)ots. Going beyond focusing on a single locomotion skill, we develop a general control solution that can be used for a range of dynamic bipedal skills, from periodic walking and running to aperiodic jumping and standing. Our RL-based controller incorporates a novel dual-history architecture, utilizing both a long-term and short-term input/output (I/O) history of the robot. This control architecture, when trained through the proposed end-to-end RL approach, consistently outperforms other methods across a diverse range of skills in both simulation and the real world. The study also delves into the adaptivity and robustness introduced by the proposed RL system in developing locomotion controllers. We demonstrate that the proposed architecture can adapt to both time-invariant dynamics shifts and time-variant changes, such as contact events, by effectively using the robot’s I/O history. Additionally, we identify task randomization as another key source of robustness, fostering better task generalization and compliance to disturbances. The resulting control policies can be successfully deployed on Cassie, a torque-controlled human-sized bipedal robot. This work pushes the limits of agility for bipedal robots through extensive real-world experiments. We demonstrate a diverse range of locomotion skills, including: robust standing, versatile walking, fast running with a demonstration of a 400-meter dash, and a diverse set of jumping skills, such as standing long jumps and high jumps.
This paper presents a comprehensive study on using deep reinforcement learning (RL) to create dynamic locomotion controllers for bipedal rob… (see more)ots. Going beyond focusing on a single locomotion skill, we develop a general control solution that can be used for a range of dynamic bipedal skills, from periodic walking and running to aperiodic jumping and standing. Our RL-based controller incorporates a novel dual-history architecture, utilizing both a long-term and short-term input/output (I/O) history of the robot. This control architecture, when trained through the proposed end-to-end RL approach, consistently outperforms other methods across a diverse range of skills in both simulation and the real world. The study also delves into the adaptivity and robustness introduced by the proposed RL system in developing locomotion controllers. We demonstrate that the proposed architecture can adapt to both time-invariant dynamics shifts and time-variant changes, such as contact events, by effectively using the robot’s I/O history. Additionally, we identify task randomization as another key source of robustness, fostering better task generalization and compliance to disturbances. The resulting control policies can be successfully deployed on Cassie, a torque-controlled human-sized bipedal robot. This work pushes the limits of agility for bipedal robots through extensive real-world experiments. We demonstrate a diverse range of locomotion skills, including: robust standing, versatile walking, fast running with a demonstration of a 400-meter dash, and a diverse set of jumping skills, such as standing long jumps and high jumps.
This paper presents a comprehensive study on using deep reinforcement learning (RL) to create dynamic locomotion controllers for bipedal rob… (see more)ots. Going beyond focusing on a single locomotion skill, we develop a general control solution that can be used for a range of dynamic bipedal skills, from periodic walking and running to aperiodic jumping and standing. Our RL-based controller incorporates a novel dual-history architecture, utilizing both a long-term and short-term input/output (I/O) history of the robot. This control architecture, when trained through the proposed end-to-end RL approach, consistently outperforms other methods across a diverse range of skills in both simulation and the real world. The study also delves into the adaptivity and robustness introduced by the proposed RL system in developing locomotion controllers. We demonstrate that the proposed architecture can adapt to both time-invariant dynamics shifts and time-variant changes, such as contact events, by effectively using the robot’s I/O history. Additionally, we identify task randomization as another key source of robustness, fostering better task generalization and compliance to disturbances. The resulting control policies can be successfully deployed on Cassie, a torque-controlled human-sized bipedal robot. This work pushes the limits of agility for bipedal robots through extensive real-world experiments. We demonstrate a diverse range of locomotion skills, including: robust standing, versatile walking, fast running with a demonstration of a 400-meter dash, and a diverse set of jumping skills, such as standing long jumps and high jumps.
This paper presents a comprehensive study on using deep reinforcement learning (RL) to create dynamic locomotion controllers for bipedal rob… (see more)ots. Going beyond focusing on a single locomotion skill, we develop a general control solution that can be used for a range of dynamic bipedal skills, from periodic walking and running to aperiodic jumping and standing. Our RL-based controller incorporates a novel dual-history architecture, utilizing both a long-term and short-term input/output (I/O) history of the robot. This control architecture, when trained through the proposed end-to-end RL approach, consistently outperforms other methods across a diverse range of skills in both simulation and the real world. The study also delves into the adaptivity and robustness introduced by the proposed RL system in developing locomotion controllers. We demonstrate that the proposed architecture can adapt to both time-invariant dynamics shifts and time-variant changes, such as contact events, by effectively using the robot’s I/O history. Additionally, we identify task randomization as another key source of robustness, fostering better task generalization and compliance to disturbances. The resulting control policies can be successfully deployed on Cassie, a torque-controlled human-sized bipedal robot. This work pushes the limits of agility for bipedal robots through extensive real-world experiments. We demonstrate a diverse range of locomotion skills, including: robust standing, versatile walking, fast running with a demonstration of a 400-meter dash, and a diverse set of jumping skills, such as standing long jumps and high jumps.
