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bayesian inference

A Bayesian inference transcription factor activity model for the analysis of single-cell transcriptomes


Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful experimental approach to study cellular heterogeneity. One of the challenges in scRNA-seq data analysis is integrating different types of biological data to consistently recognize discrete biological functions and regulatory mechanisms of cells, such as transcription factor activities and gene regulatory networks in distinct cell populations. We have developed an approach to infer transcription factor activities from scRNA-seq data that leverages existing biological data on transcription factor binding sites. We show that the inferred transcription factor activities for key cell types identify regulatory transcription factors that are known to mechanistically control cell function and cell fate. The BITFAM approach not only identifies biologically meaningful transcription factor activities, but also provides valuable insights into underlying transcription factor regulatory mechanisms.

Faculty Opinions Recommended Article: A Bayesian inference transcription factor activity model for the analysis of single-cell transcriptomes.


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What is Machine Learning? A Primer for the Epidemiologist


Machine learning is a branch of computer science that has the potential to transform epidemiologic sciences. Amid a growing focus on "Big Data," it offers epidemiologists new tools to tackle problems for which classical methods are not well-suited. In order to critically evaluate the value of integrating machine learning algorithms and existing methods, however, it is essential to address language and technical barriers between the two fields that can make it difficult for epidemiologists to read and assess machine learning studies. Here, we provide an overview of the concepts and terminology used in machine learning literature, which encompasses a diverse set of tools with goals ranging from prediction to classification to clustering. We provide a brief introduction to 5 common machine learning algorithms and 4 ensemble-based approaches. We then summarize epidemiologic applications of machine learning techniques in the published literature. We recommend approaches to incorporate machine learning in epidemiologic research and discuss opportunities and challenges for integrating machine learning and existing epidemiologic research methods. Machine learning is a branch of computer science that broadly aims to enable computers to "learn" without being directly programmed (1). It has origins in the artificial intelligence movement of the 1950s and emphasizes practical objectives and applications, particularly prediction and optimization. Computers "learn" in machine learning by improving their performance at tasks through "experience" (2, p. xv). In practice, "experience" usually means fitting to data; hence, there is not a clear boundary between machine learning and statistical approaches. Indeed, whether a given methodology is considered "machine learning" or "statistical" often reflects its history as much as genuine differences, and many algorithms (e.g., least absolute shrinkage and selection operator (LASSO), stepwise regression) may or may not be considered machine learning depending on who you ask. Still, despite methodological similarities, machine learning is philosophically and practically distinguishable. At the liberty of (considerable) oversimplification, machine learning generally emphasizes predictive accuracy over hypothesis-driven inference, usually focusing on large, high-dimensional (i.e., having many covariates) data sets (3, 4). Regardless of the precise distinction between approaches, in practice, machine learning offers epidemiologists important tools. In particular, a growing focus on "Big Data" emphasizes problems and data sets for which machine learning algorithms excel while more commonly used statistical approaches struggle. This primer provides a basic introduction to machine learning with the aim of providing readers a foundation for critically reading studies based on these methods and a jumping-off point for those interested in using machine learning techniques in epidemiologic research.

The World of Reality, Causality and Real Artificial Intelligence: Exposing the Great Unknown Unknowns


"All men by nature desire to know." - Aristotle "He who does not know what the world is does not know where he is." - Marcus Aurelius "If I have seen further, it is by standing on the shoulders of giants." "The universe is a giant causal machine. The world is "at the bottom" governed by causal algorithms. Our bodies are causal machines. Our brains and minds are causal AI computers". The 3 biggest unknown unknowns are described and analyzed in terms of human intelligence and machine intelligence. A deep understanding of reality and its causality is to revolutionize the world, its science and technology, AI machines including. The content is the intro of Real AI Project Confidential Report: How to Engineer Man-Machine Superintelligence 2025: AI for Everything and Everyone (AI4EE). It is all a power set of {known, unknown; known unknown}, known knowns, known unknowns, unknown knowns, and unknown unknowns, like as the material universe's material parts: about 4.6% of baryonic matter, about 26.8% of dark matter, and about 68.3% of dark energy. There are a big number of sciences, all sorts and kinds, hard sciences and soft sciences. But what we are still missing is the science of all sciences, the Science of the World as a Whole, thus making it the biggest unknown unknowns. It is what man/AI does not know what it does not know, neither understand, nor aware of its scope and scale, sense and extent. "the universe consists of objects having various qualities and standing in various relationships" (Whitehead, Russell), "the world is the totality of states of affairs" (D. "World of physical objects and events, including, in particular, biological beings; World of mental objects and events; World of objective contents of thought" (K. How the world is still an unknown unknown one could see from the most popular lexical ontology, WordNet,see supplement. The construct of the world is typically missing its essential meaning, "the world as a whole", the world of reality, the ultimate totality of all worlds, universes, and realities, beings, things, and entities, the unified totalities. The world or reality or being or existence is "all that is, has been and will be". Of which the physical universe and cosmos is a key part, as "the totality of space and times and matter and energy, with all causative fundamental interactions".

Would a robot trust you? Developmental robotics model of trust and theory of mind


The technological revolution taking place in the fields of robotics and artificial intelligence seems to indicate a future shift in our human-centred social paradigm towards a greater inclusion of artificial cognitive agents in our everyday environments. This means that collaborative scenarios between humans and robots will become more frequent and will have a deeper impact on everyday life. In this setting, research regarding trust in human–robot interactions (HRI) assumes a major importance in order to ensure the highest quality of the interaction itself, as trust directly affects the willingness of people to accept information produced by a robot and to cooperate with it. Many studies have already explored trust that humans give to robots and how this can be enhanced by tuning both the design and the behaviour of the machine, but not so much research has focused on the opposite scenario, that is the trust that artificial agents can assign to people. Despite this, the latter is a critical factor in joint tasks where humans and robots depend on each other's effort to achieve a shared goal: whereas a robot can fail, so can a person. For an artificial agent to know when to trust or distrust somebody and adapt its plans to this prediction can make all the difference in the success or failure of the task. Our work is centred on the design and development of an artificial cognitive architecture for a humanoid autonomous robot that incorporates trust, theory of mind (ToM) and episodic memory, as we believe these are the three key factors for the purpose of estimating the trustworthiness of others. We have tested our architecture on an established developmental psychology experiment [1] and the results we obtained confirm that our approach successfully models trust mechanisms and dynamics in cognitive robots. Trust is a fundamental, unavoidable component of social interactions that can be defined as the willingness of a party (the trustor) to rely on the actions of another party (the trustee), with the former having no control over the latter [2].

Improving Label Quality by Jointly Modeling Items and Annotators Artificial Intelligence

We propose a fully Bayesian framework for learning ground truth labels from noisy annotators. Our framework ensures scalability by factoring a generative, Bayesian soft clustering model over label distributions into the classic David and Skene joint annotator-data model. Earlier research along these lines has neither fully incorporated label distributions nor explored clustering by annotators only or data only. Our framework incorporates all of these properties as: (1) a graphical model designed to provide better ground truth estimates of annotator responses as input to \emph{any} black box supervised learning algorithm, and (2) a standalone neural model whose internal structure captures many of the properties of the graphical model. We conduct supervised learning experiments using both models and compare them to the performance of one baseline and a state-of-the-art model.

The Principles of Deep Learning Theory Artificial Intelligence

This book develops an effective theory approach to understanding deep neural networks of practical relevance. Beginning from a first-principles component-level picture of networks, we explain how to determine an accurate description of the output of trained networks by solving layer-to-layer iteration equations and nonlinear learning dynamics. A main result is that the predictions of networks are described by nearly-Gaussian distributions, with the depth-to-width aspect ratio of the network controlling the deviations from the infinite-width Gaussian description. We explain how these effectively-deep networks learn nontrivial representations from training and more broadly analyze the mechanism of representation learning for nonlinear models. From a nearly-kernel-methods perspective, we find that the dependence of such models' predictions on the underlying learning algorithm can be expressed in a simple and universal way. To obtain these results, we develop the notion of representation group flow (RG flow) to characterize the propagation of signals through the network. By tuning networks to criticality, we give a practical solution to the exploding and vanishing gradient problem. We further explain how RG flow leads to near-universal behavior and lets us categorize networks built from different activation functions into universality classes. Altogether, we show that the depth-to-width ratio governs the effective model complexity of the ensemble of trained networks. By using information-theoretic techniques, we estimate the optimal aspect ratio at which we expect the network to be practically most useful and show how residual connections can be used to push this scale to arbitrary depths. With these tools, we can learn in detail about the inductive bias of architectures, hyperparameters, and optimizers.

Leveraging Language to Learn Program Abstractions and Search Heuristics Artificial Intelligence

Inductive program synthesis, or inferring programs from examples of desired behavior, offers a general paradigm for building interpretable, robust, and generalizable machine learning systems. Effective program synthesis depends on two key ingredients: a strong library of functions from which to build programs, and an efficient search strategy for finding programs that solve a given task. We introduce LAPS (Language for Abstraction and Program Search), a technique for using natural language annotations to guide joint learning of libraries and neurally-guided search models for synthesis. When integrated into a state-of-the-art library learning system (DreamCoder), LAPS produces higher-quality libraries and improves search efficiency and generalization on three domains -- string editing, image composition, and abstract reasoning about scenes -- even when no natural language hints are available at test time.

Rational Shapley Values Artificial Intelligence

Explaining the predictions of opaque machine learning algorithms is an important and challenging task, especially as complex models are increasingly used to assist in high-stakes decisions such as those arising in healthcare and finance. Most popular tools for post-hoc explainable artificial intelligence (XAI) are either insensitive to context (e.g., feature attributions) or difficult to summarize (e.g., counterfactuals). In this paper, I introduce \emph{rational Shapley values}, a novel XAI method that synthesizes and extends these seemingly incompatible approaches in a rigorous, flexible manner. I leverage tools from decision theory and causal modeling to formalize and implement a pragmatic approach that resolves a number of known challenges in XAI. By pairing the distribution of random variables with the appropriate reference class for a given explanation task, I illustrate through theory and experiments how user goals and knowledge can inform and constrain the solution set in an iterative fashion. The method compares favorably to state of the art XAI tools in a range of quantitative and qualitative comparisons.

On the benefits of maximum likelihood estimation for Regression and Forecasting Artificial Intelligence

We advocate for a practical Maximum Likelihood Estimation (MLE) approach for regression and forecasting, as an alternative to the typical approach of Empirical Risk Minimization (ERM) for a specific target metric. This approach is better suited to capture inductive biases such as prior domain knowledge in datasets, and can output post-hoc estimators at inference time that can optimize different types of target metrics. We present theoretical results to demonstrate that our approach is always competitive with any estimator for the target metric under some general conditions, and in many practical settings (such as Poisson Regression) can actually be much superior to ERM. We demonstrate empirically that our method instantiated with a well-designed general purpose mixture likelihood family can obtain superior performance over ERM for a variety of tasks across time-series forecasting and regression datasets with different data distributions.