The interaction of a protein with its environment can be understood and controlled via its 3D structure. Experimental methods for protein structure determination, such as X-ray crystallography or cryogenic electron microscopy, shed light on biological processes but introduce challenging inverse problems. Learning-based approaches have emerged as accurate and efficient methods to solve these inverse problems for 3D structure determination, but are specialized for a predefined type of measurement. Here, we introduce a versatile framework to turn raw biophysical measurements of varying types into 3D atomic models. Our method combines a physics-based forward model of the measurement process with a pretrained generative model providing a task-agnostic, data-driven prior. Our method outperforms posterior sampling baselines on both linear and non-linear inverse problems. In particular, it is the first diffusion-based method for refining atomic models from cryo-EM density maps.

Recent advances in probabilistic deep learning enable efficient amortized Bayesian inference in settings where the likelihood function is only implicitly defined by a simulation program (simulation-based inference; SBI). But how faithful is such inference if the simulation represents reality somewhat inaccurately, that is, if the true system behavior at test time deviates from the one seen during training? We conceptualize the types of such model misspecification arising in SBI and systematically investigate how the performance of neural posterior approximators gradually deteriorates as a consequence, making inference results less and less trustworthy. To notify users about this problem, we propose a new misspecification measure that can be trained in an unsupervised fashion (i.e., without training data from the true distribution) and reliably detects model misspecification at test time. Our experiments clearly demonstrate the utility of our new measure both on toy examples with an analytical ground-truth and on representative scientific tasks in cell biology, cognitive decision making, disease outbreak dynamics, and computer vision. We show how the proposed misspecification test warns users about suspicious outputs, raises an alarm when predictions are not trustworthy, and guides model designers in their search for better simulators.

This work studies the challenge of aligning large language models (LLMs) with offline preference data. We focus on alignment by Reinforcement Learning from Human Feedback (RLHF) in particular. While popular preference optimization methods exhibit good empirical performance in practice, they are not theoretically guaranteed to converge to the optimal policy and can provably fail when the data coverage is sparse by classical offline reinforcement learning (RL) results. On the other hand, a recent line of work has focused on theoretically motivated preference optimization methods with provable guarantees, but these are not computationally efficient for large-scale applications like LLM alignment. To bridge this gap, we propose SPAC, a new offline preference optimization method with self-play, inspired by the on-average pessimism technique from the offline RL literature, to be the first provable and scalable approach to LLM alignment. We both provide theoretical analysis for its convergence under single-policy concentrability for the general function approximation setting and demonstrate its competitive empirical performance for LLM alignment on a 7B Mistral model with Open LLM Leaderboard evaluations.

In recent years, solving optimization problems involving black-box simulators has become a point of focus for the machine learning community due to their ubiquity in science and engineering. The simulators describe a forward process $f_{\mathrm{sim}}: (\psi, x) \rightarrow y$ from simulation parameters $\psi$ and input data $x$ to observations $y$, and the goal of the optimization problem is to find parameters $\psi$ that minimize a desired loss function. Sophisticated optimization algorithms typically require gradient information regarding the forward process, $f_{\mathrm{sim}}$, with respect to the parameters $\psi$. However, obtaining gradients from black-box simulators can often be prohibitively expensive or, in some cases, impossible. Furthermore, in many applications, practitioners aim to solve a set of related problems. Thus, starting the optimization ``ab initio", i.e. from scratch, each time might be inefficient if the forward model is expensive to evaluate. To address those challenges, this paper introduces a novel method for solving classes of similar black-box optimization problems by learning an active learning policy that guides a differentiable surrogate's training and uses the surrogate's gradients to optimize the simulation parameters with gradient descent. After training the policy, downstream optimization of problems involving black-box simulators requires up to $\sim$90\% fewer expensive simulator calls compared to baselines such as local surrogate-based approaches, numerical optimization, and Bayesian methods.

Current approaches to model-based offline Reinforcement Learning (RL) often incorporate uncertainty-based reward penalization to address the distributional shift problem. While these approaches have achieved some success, we argue that this penalization introduces excessive conservatism, potentially resulting in suboptimal policies through underestimation. We identify as an important cause of over-penalization the lack of a reliable uncertainty estimator capable of propagating uncertainties in the Bellman operator. The common approach to calculating the penalty term relies on sampling-based uncertainty estimation, resulting in high variance. To address this challenge, we propose a novel method termed Moment Matching Offline Model-Based Policy Optimization (MOMBO). MOMBO learns a Q-function using moment matching, which allows us to deterministically propagate uncertainties through the Q-function. We evaluate MOMBO's performance across various environments and demonstrate empirically that MOMBO is a more stable and sample-efficient approach.

High-dimensional Bayesian optimization (BO) tasks such as molecular design often require > 10,000 function evaluations before obtaining meaningful results. While methods like sparse variational Gaussian processes (SVGPs) reduce computational requirements in these settings, the underlying approximations result in suboptimal data acquisitions that slow the progress of optimization. In this paper we modify SVGPs to better align with the goals of BO: targeting informed data acquisition rather than global posterior fidelity. Using the framework of utility-calibrated variational inference, we unify GP approximation and data acquisition into a joint optimization problem, thereby ensuring optimal decisions under a limited computational budget. Our approach can be used with any decision-theoretic acquisition function and is compatible with trust region methods like TuRBO. We derive efficient joint objectives for the expected improvement and knowledge gradient acquisition functions in both the standard and batch BO settings. Our approach outperforms standard SVGPs on high-dimensional benchmark tasks in control and molecular design.

Educational Data Mining (EDM) is a promising field, where data mining is widely used for predicting students performance. One of the most prevalent and recent challenge that higher education faces today is making students skillfully employable. Institutions possess large volume of data; still they are unable to reveal knowledge and guide their students. Data in education is generally very large, multidimensional and unbalanced in nature. Process of extracting knowledge from such data has its own set of problems and is a very complicated task. In this paper, Engineering and MCA (Masters in Computer Applications) students data is collected from various universities and institutes pan India. The dataset is large, unbalanced and multidimensional in nature. A cluster based model is presented in this paper, which, when applied at preprocessing stage helps in parsimonious selection of variables and improves the performance of predictive algorithms. Hence, facilitate in better prediction of Students Employability.

Olfaction sensing in autonomous robotics faces challenges in dynamic operations, energy efficiency, and edge processing. It necessitates a machine learning algorithm capable of managing real-world odor interference, ensuring resource efficiency for mobile robotics, and accurately estimating gas features for critical tasks such as odor mapping, localization, and alarm generation. This paper introduces a hybrid approach that exploits neuromorphic computing in combination with probabilistic inference to address these demanding requirements. Our approach implements a combination of a convolutional spiking neural network for feature extraction and a Bayesian spiking neural network for odor detection and identification. The developed algorithm is rigorously tested on a dataset for sensor drift compensation for robustness evaluation. Additionally, for efficiency evaluation, we compare the energy consumption of our model with a non-spiking machine learning algorithm under identical dataset and operating conditions. Our approach demonstrates superior efficiency alongside comparable accuracy outcomes.

Reconstructing jets, which provide vital insights into the properties and histories of subatomic particles produced in high-energy collisions, is a main problem in data analyses in collider physics. This intricate task deals with estimating the latent structure of a jet (binary tree) and involves parameters such as particle energy, momentum, and types. While Bayesian methods offer a natural approach for handling uncertainty and leveraging prior knowledge, they face significant challenges due to the super-exponential growth of potential jet topologies as the number of observed particles increases. To address this, we introduce a Combinatorial Sequential Monte Carlo approach for inferring jet latent structures. As a second contribution, we leverage the resulting estimator to develop a variational inference algorithm for parameter learning. Building on this, we introduce a variational family using a pseudo-marginal framework for a fully Bayesian treatment of all variables, unifying the generative model with the inference process. We illustrate our method's effectiveness through experiments using data generated with a collider physics generative model, highlighting superior speed and accuracy across a range of tasks.

Representing uncertainty in causal discovery is a crucial component for experimental design, and more broadly, for safe and reliable causal decision making. Bayesian Causal Discovery (BCD) offers a principled approach to encapsulating this uncertainty. Unlike non-Bayesian causal discovery, which relies on a single estimated causal graph and model parameters for assessment, evaluating BCD presents challenges due to the nature of its inferred quantity - the posterior distribution. As a result, the research community has proposed various metrics to assess the quality of the approximate posterior. However, there is, to date, no consensus on the most suitable metric(s) for evaluation. In this work, we reexamine this question by dissecting various metrics and understanding their limitations. Through extensive empirical evaluation, we find that many existing metrics fail to exhibit a strong correlation with the quality of approximation to the true posterior, especially in scenarios with low sample sizes where BCD is most desirable. We highlight the suitability (or lack thereof) of these metrics under two distinct factors: the identifiability of the underlying causal model and the quantity of available data. Both factors affect the entropy of the true posterior, indicating that the current metrics are less fitting in settings of higher entropy. Our findings underline the importance of a more nuanced evaluation of new methods by taking into account the nature of the true posterior, as well as guide and motivate the development of new evaluation procedures for this challenge.