Three-Dimensional (3D) chromatin interactions, such as enhancer-promoter interactions (EPIs), loops, Topologically Associating Domains (TADs), and A/B compartments play critical roles in a wide range of cellular processes by regulating gene expression. Recent development of chromatin conformation capture technologies has enabled genome-wide profiling of various 3D structures, even with single cells. However, current catalogs of 3D structures remain incomplete and unreliable due to differences in technology, tools, and low data resolution. Machine learning methods have emerged as an alternative to obtain missing 3D interactions and/or improve resolution. Such methods frequently use genome annotation data (ChIP-seq, DNAse-seq, etc.), DNA sequencing information (k-mers, Transcription Factor Binding Site (TFBS) motifs), and other genomic properties to learn the associations between genomic features and chromatin interactions. In this review, we discuss computational tools for predicting three types of 3D interactions (EPIs, chromatin interactions, TAD boundaries) and analyze their pros and cons. We also point out obstacles of computational prediction of 3D interactions and suggest future research directions.

Machine learning (ML) is vulnerable to inference (e.g., membership inference, property inference, and data reconstruction) attacks that aim to infer the private information of training data or dataset. Existing defenses are only designed for one specific type of attack and sacrifice significant utility or are soon broken by adaptive attacks. We address these limitations by proposing an information-theoretic defense framework, called Inf2Guard, against the three major types of inference attacks. Our framework, inspired by the success of representation learning, posits that learning shared representations not only saves time/costs but also benefits numerous downstream tasks. Generally, Inf2Guard involves two mutual information objectives, for privacy protection and utility preservation, respectively. Inf2Guard exhibits many merits: it facilitates the design of customized objectives against the specific inference attack; it provides a general defense framework which can treat certain existing defenses as special cases; and importantly, it aids in deriving theoretical results, e.g., inherent utility-privacy tradeoff and guaranteed privacy leakage. Extensive evaluations validate the effectiveness of Inf2Guard for learning privacy-preserving representations against inference attacks and demonstrate the superiority over the baselines.

This book aims to provide a working introduction to the emerging fusion of modern statistical inference - aka machine learning (ML) or artificial intelligence (AI) - and causal inference methods. The book is aimed at upper level undergraduates and master's-level students as well as doctoral students focusing on applied empirical research. A sufficient background for the core material is one semester of introductory econometrics and one semester of machine learning. We hope the book is also useful to empirical researchers looking to apply modern methods in their work. The book provides an overview of key ideas in both predictive inference and causal inference and shows how predictive tools are key ingredients to answering many causal questions.

We prove non-asymptotic error bounds for particle gradient descent (PGD)~(Kuntz et al., 2023), a recently introduced algorithm for maximum likelihood estimation of large latent variable models obtained by discretizing a gradient flow of the free energy. We begin by showing that, for models satisfying a condition generalizing both the log-Sobolev and the Polyak--{\L}ojasiewicz inequalities (LSI and P{\L}I, respectively), the flow converges exponentially fast to the set of minimizers of the free energy. We achieve this by extending a result well-known in the optimal transport literature (that the LSI implies the Talagrand inequality) and its counterpart in the optimization literature (that the P{\L}I implies the so-called quadratic growth condition), and applying it to our new setting. We also generalize the Bakry--\'Emery Theorem and show that the LSI/P{\L}I generalization holds for models with strongly concave log-likelihoods. For such models, we further control PGD's discretization error, obtaining non-asymptotic error bounds. While we are motivated by the study of PGD, we believe that the inequalities and results we extend may be of independent interest.

Deep Gaussian processes have recently been proposed as natural objects to fit, similarly to deep neural networks, possibly complex features present in modern data samples, such as compositional structures. Adopting a Bayesian nonparametric approach, it is natural to use deep Gaussian processes as prior distributions, and use the corresponding posterior distributions for statistical inference. We introduce the deep Horseshoe Gaussian process Deep-HGP, a new simple prior based on deep Gaussian processes with a squared-exponential kernel, that in particular enables data-driven choices of the key lengthscale parameters. For nonparametric regression with random design, we show that the associated tempered posterior distribution recovers the unknown true regression curve optimally in terms of quadratic loss, up to a logarithmic factor, in an adaptive way. The convergence rates are simultaneously adaptive to both the smoothness of the regression function and to its structure in terms of compositions. The dependence of the rates in terms of dimension are explicit, allowing in particular for input spaces of dimension increasing with the number of observations.

When machine learning systems meet real world applications, accuracy is only one of several requirements.

These appendices provide supplementary details and results of BAST. Appendix A contains additional details on Bayesian estimation and prediction. Supplementary simulation details and results including hyperparameter tuning and computation time can be found in Appendix B. Finally, Appendix C provides the proof of Proposition 1. Appendix A.1 Estimation This appendix provides details on the Markov chain Monte Carlo (MCMC) algorithm discussed in Section 3.1. This probability specification works well in our experiments, but one can modify it if desired. Appendix A.2 Prediction in Two-dimensional Constrained Domains In this subsection we provide details on specifying the neighbor set N To sample the cluster membership of u, we need to determine the cluster memberships for vertices on the domain boundary, which can be done by, for instance, assigning a boundary vertex to the same cluster as its nearest vertex in S with respect to the graph distance in the CDT mesh (when the number of vertices in the CDT graph is large, we expect this to well approximate the geodesic distance).

We introduce the forward-backward (FB) representation of the dynamics of a reward-free Markov decision process. It provides explicit near-optimal policies for any reward specified a posteriori. During an unsupervised phase, we use rewardfree interactions with the environment to learn two representations via off-the-shelf deep learning methods and temporal difference (TD) learning. In the test phase, a reward representation is estimated either from reward observations or an explicit reward description (e.g., a target state). The optimal policy for that reward is directly obtained from these representations, with no planning.

We provide improved gap-dependent regret bounds for reinforcement learning in finite episodic Markov decision processes. Compared to prior work, our bounds depend on alternative definitions of gaps. These definitions are based on the insight that, in order to achieve a favorable regret, an algorithm does not need to learn how to behave optimally in states that are not reached by an optimal policy. We prove tighter upper regret bounds for optimistic algorithms and accompany them with new information-theoretic lower bounds for a large class of MDPs. Our results show that optimistic algorithms can not achieve the information-theoretic lower bounds even in deterministic MDPs unless there is a unique optimal policy.

We introduce the forward-backward (FB) representation of the dynamics of a reward-free Markov decision process. It provides explicit near-optimal policies for any reward specified a posteriori. During an unsupervised phase, we use rewardfree interactions with the environment to learn two representations via off-the-shelf deep learning methods and temporal difference (TD) learning. In the test phase, a reward representation is estimated either from reward observations or an explicit reward description (e.g., a target state). The optimal policy for that reward is directly obtained from these representations, with no planning.