Gene set analysis, a popular approach for analysing high-throughput gene expression data, aims to identify sets of genes that show enriched expression patterns between two conditions. In addition to the multitude of methods available for this task, users are typically left with many options when creating the required input and specifying the internal parameters of the chosen method. This flexibility can lead to uncertainty about the 'right' choice, further reinforced by a lack of evidence-based guidance. Especially when their statistical experience is scarce, this uncertainty might entice users to produce preferable results using a 'trial-and-error' approach. While it may seem unproblematic at first glance, this practice can be viewed as a form of 'cherry-picking' and cause an optimistic bias, rendering the results non-replicable on independent data. After this problem has attracted a lot of attention in the context of classical hypothesis testing, we now aim to raise awareness of such over-optimism in the different and more complex context of gene set analyses. We mimic a hypothetical researcher who systematically selects the analysis variants yielding their preferred results, thereby considering three distinct goals they might pursue. Using a selection of popular gene set analysis methods, we tweak the results in this way for two frequently used benchmark gene expression data sets. Our study indicates that the potential for over-optimism is particularly high for a group of methods frequently used despite being commonly criticised. We conclude by providing practical recommendations to counter over-optimism in research findings in gene set analysis and beyond.
相關內容
In this article, we study the Fekete problem in segmental and combined nodal-segmental univariate polynomial interpolation by investigating sets of segments, or segments combined with nodes, such that the Vandermonde determinant for the respective polynomial interpolation problem is maximized. For particular families of segments, we will be able to find explicit solutions of the corresponding maximization problem. The quality of the Fekete segments depends hereby strongly on the utilized normalization of the segmental information in the Vandermonde matrix. To measure the quality of the Fekete segments in interpolation, we analyse the asymptotic behaviour of the generalized Lebesgue constant linked to the interpolation problem. For particular sets of Fekete segments we will get, similar to the nodal case, a favourable logarithmic growth of this constant.
We consider the general class of time-homogeneous stochastic dynamical systems, both discrete and continuous, and study the problem of learning a representation of the state that faithfully captures its dynamics. This is instrumental to learning the transfer operator or the generator of the system, which in turn can be used for numerous tasks, such as forecasting and interpreting the system dynamics. We show that the search for a good representation can be cast as an optimization problem over neural networks. Our approach is supported by recent results in statistical learning theory, highlighting the role of approximation error and metric distortion in the learning problem. The objective function we propose is associated with projection operators from the representation space to the data space, overcomes metric distortion, and can be empirically estimated from data. In the discrete-time setting, we further derive a relaxed objective function that is differentiable and numerically well-conditioned. We compare our method against state-of-the-art approaches on different datasets, showing better performance across the board.
The recent paper (IEEE Trans. IT 69, 1680) introduced an analytical method for calculating the channel capacity without the need for iteration. This method has certain limitations that restrict its applicability. Furthermore, the paper does not provide an explanation as to why the channel capacity can be solved analytically in this particular case. In order to broaden the scope of this method and address its limitations, we turn our attention to the reverse em-problem, proposed by Toyota (Information Geometry, 3, 1355 (2020)). This reverse em-problem involves iteratively applying the inverse map of the em iteration to calculate the channel capacity, which represents the maximum mutual information. However, several open problems remained unresolved in Toyota's work. To overcome these challenges, we formulate the reverse em-problem based on Bregman divergence and provide solutions to these open problems. Building upon these results, we transform the reverse em-problem into em-problems and derive a non-iterative formula for the reverse em-problem. This formula can be viewed as a generalization of the aforementioned analytical calculation method. Importantly, this derivation sheds light on the information geometrical structure underlying this special case. By effectively addressing the limitations of the previous analytical method and providing a deeper understanding of the underlying information geometrical structure, our work significantly expands the applicability of the proposed method for calculating the channel capacity without iteration.
Confidence intervals based on the central limit theorem (CLT) are a cornerstone of classical statistics. Despite being only asymptotically valid, they are ubiquitous because they permit statistical inference under weak assumptions and can often be applied to problems even when nonasymptotic inference is impossible. This paper introduces time-uniform analogues of such asymptotic confidence intervals, adding to the literature on confidence sequences (CS) -- sequences of confidence intervals that are uniformly valid over time -- which provide valid inference at arbitrary stopping times and incur no penalties for "peeking" at the data, unlike classical confidence intervals which require the sample size to be fixed in advance. Existing CSs in the literature are nonasymptotic, enjoying finite-sample guarantees but not the aforementioned broad applicability of asymptotic confidence intervals. This work provides a definition for "asymptotic CSs" and a general recipe for deriving them. Asymptotic CSs forgo nonasymptotic validity for CLT-like versatility and (asymptotic) time-uniform guarantees. While the CLT approximates the distribution of a sample average by that of a Gaussian for a fixed sample size, we use strong invariance principles (stemming from the seminal 1960s work of Strassen) to uniformly approximate the entire sample average process by an implicit Gaussian process. As an illustration, we derive asymptotic CSs for the average treatment effect in observational studies (for which nonasymptotic bounds are essentially impossible to derive even in the fixed-time regime) as well as randomized experiments, enabling causal inference in sequential environments.
This work presents a comparative review and classification between some well-known thermodynamically consistent models of hydrogel behavior in a large deformation setting, specifically focusing on solvent absorption/desorption and its impact on mechanical deformation and network swelling. The proposed discussion addresses formulation aspects, general mathematical classification of the governing equations, and numerical implementation issues based on the finite element method. The theories are presented in a unified framework demonstrating that, despite not being evident in some cases, all of them follow equivalent thermodynamic arguments. A detailed numerical analysis is carried out where Taylor-Hood elements are employed in the spatial discretization to satisfy the inf-sup condition and to prevent spurious numerical oscillations. The resulting discrete problems are solved using the FEniCS platform through consistent variational formulations, employing both monolithic and staggered approaches. We conduct benchmark tests on various hydrogel structures, demonstrating that major differences arise from the chosen volumetric response of the hydrogel. The significance of this choice is frequently underestimated in the state-of-the-art literature but has been shown to have substantial implications on the resulting hydrogel behavior.
Backtracking linesearch is the de facto approach for minimizing continuously differentiable functions with locally Lipschitz gradient. In recent years, it has been shown that in the convex setting it is possible to avoid linesearch altogether, and to allow the stepsize to adapt based on a local smoothness estimate without any backtracks or evaluations of the function value. In this work we propose an adaptive proximal gradient method, adaPG, that uses novel estimates of the local smoothness modulus which leads to less conservative stepsize updates and that can additionally cope with nonsmooth terms. This idea is extended to the primal-dual setting where an adaptive three-term primal-dual algorithm, adaPD, is proposed which can be viewed as an extension of the PDHG method. Moreover, in this setting the "essentially" fully adaptive variant adaPD$^+$ is proposed that avoids evaluating the linear operator norm by invoking a backtracking procedure, that, remarkably, does not require extra gradient evaluations. Numerical simulations demonstrate the effectiveness of the proposed algorithms compared to the state of the art.
We propose an operator learning approach to accelerate geometric Markov chain Monte Carlo (MCMC) for solving infinite-dimensional nonlinear Bayesian inverse problems. While geometric MCMC employs high-quality proposals that adapt to posterior local geometry, it requires computing local gradient and Hessian information of the log-likelihood, incurring a high cost when the parameter-to-observable (PtO) map is defined through expensive model simulations. We consider a delayed-acceptance geometric MCMC method driven by a neural operator surrogate of the PtO map, where the proposal is designed to exploit fast surrogate approximations of the log-likelihood and, simultaneously, its gradient and Hessian. To achieve a substantial speedup, the surrogate needs to be accurate in predicting both the observable and its parametric derivative (the derivative of the observable with respect to the parameter). Training such a surrogate via conventional operator learning using input--output samples often demands a prohibitively large number of model simulations. In this work, we present an extension of derivative-informed operator learning [O'Leary-Roseberry et al., J. Comput. Phys., 496 (2024)] using input--output--derivative training samples. Such a learning method leads to derivative-informed neural operator (DINO) surrogates that accurately predict the observable and its parametric derivative at a significantly lower training cost than the conventional method. Cost and error analysis for reduced basis DINO surrogates are provided. Numerical studies on PDE-constrained Bayesian inversion demonstrate that DINO-driven MCMC generates effective posterior samples 3--9 times faster than geometric MCMC and 60--97 times faster than prior geometry-based MCMC. Furthermore, the training cost of DINO surrogates breaks even after collecting merely 10--25 effective posterior samples compared to geometric MCMC.
Existing schemes for demonstrating quantum computational advantage are subject to various practical restrictions, including the hardness of verification and challenges in experimental implementation. Meanwhile, analog quantum simulators have been realized in many experiments to study novel physics. In this work, we propose a quantum advantage protocol based on single-step Feynman-Kitaev verification of an analog quantum simulation, in which the verifier need only run an $O(\lambda^2)$-time classical computation, and the prover need only prepare $O(1)$ samples of a history state and perform $O(\lambda^2)$ single-qubit measurements, for a security parameter $\lambda$. We also propose a near-term feasible strategy for honest provers and discuss potential experimental realizations.
Gamification, the integration of game mechanics in non-game settings, has become increasingly prevalent in various digital platforms; however, its ethical and societal impacts are often overlooked. This paper delves into how Platonic and Aristotelian philosophies can provide a critical framework for understanding and evaluating the ethical dimensions of gamification. Plato's allegory of the cave and theory of forms are used to analyse the perception of reality in gamified environments, questioning their authenticity and the value of virtual achievements, while Aristotle's virtue ethics, with its emphasis on moderation, virtue, and eudaimonia (true and full happiness), can help assess how gamification influences user behaviour and ethical decision-making. The paper critically examines various gamification elements, such as the hero's journey, altruistic actions, badge levels, and user autonomy, through these philosophical lenses, and addresses the ethical responsibilities of gamification designers, advocating for a balanced approach that prioritizes user well-being and ethical development over commercial interests. By bridging ancient philosophical insights with modern digital culture, this research contributes to a deeper understanding of the ethical implications of gamification, emphasizing the need for responsible and virtuous design in digital applications.
We study when low coordinate degree functions (LCDF) -- linear combinations of functions depending on small subsets of entries of a vector -- can hypothesis test between high-dimensional probability measures. These functions are a generalization, proposed in Hopkins' 2018 thesis but seldom studied since, of low degree polynomials (LDP), a class widely used in recent literature as a proxy for all efficient algorithms for tasks in statistics and optimization. Instead of the orthogonal polynomial decompositions used in LDP calculations, our analysis of LCDF is based on the Efron-Stein or ANOVA decomposition, making it much more broadly applicable. By way of illustration, we prove channel universality for the success of LCDF in testing for the presence of sufficiently "dilute" random signals through noisy channels: the efficacy of LCDF depends on the channel only through the scalar Fisher information for a class of channels including nearly arbitrary additive i.i.d. noise and nearly arbitrary exponential families. As applications, we extend lower bounds against LDP for spiked matrix and tensor models under additive Gaussian noise to lower bounds against LCDF under general noisy channels. We also give a simple and unified treatment of the effect of censoring models by erasing observations at random and of quantizing models by taking the sign of the observations. These results are the first computational lower bounds against any large class of algorithms for all of these models when the channel is not one of a few special cases, and thereby give the first substantial evidence for the universality of several statistical-to-computational gaps.
注冊地址： 北京市海淀區羊坊店路18號2幢3層301-191