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This letter illustrates the opinion of the molecular dynamics (MD) community on the need to adopt a new FAIR paradigm for the use of molecular simulations. It highlights the necessity of a collaborative effort to create, establish, and sustain a database that allows findability, accessibility, interoperability, and reusability of molecular dynamics simulation data. Such a development would democratize the field and significantly improve the impact of MD simulations on life science research. This will transform our working paradigm, pushing the field to a new frontier. We invite you to support our initiative at the MDDB community (https://mddbr.eu/community/)

Valid statistical inference is crucial for decision-making but difficult to obtain in supervised learning with multimodal data, e.g., combinations of clinical features, genomic data, and medical images. Multimodal data often warrants the use of black-box algorithms, for instance, random forests or neural networks, which impede the use of traditional variable significance tests. We address this problem by proposing the use of COvariance Measure Tests (COMETs), which are calibrated and powerful tests that can be combined with any sufficiently predictive supervised learning algorithm. We apply COMETs to several high-dimensional, multimodal data sets to illustrate (i) variable significance testing for finding relevant mutations modulating drug-activity, (ii) modality selection for predicting survival in liver cancer patients with multiomics data, and (iii) modality selection with clinical features and medical imaging data. In all applications, COMETs yield results consistent with domain knowledge without requiring data-driven pre-processing which may invalidate type I error control. These novel applications with high-dimensional multimodal data corroborate prior results on the power and robustness of COMETs for significance testing. COMETs are implemented in the comets R package available on CRAN and pycomets Python library available on GitHub. Source code for reproducing all results is available at https://github.com/LucasKook/comets. All data sets used in this work are openly available.

AI-powered education technologies can support students and teachers in computer science education. However, with the recent developments in generative AI, and especially the increasingly emerging popularity of ChatGPT, the effectiveness of using large language models for solving programming tasks has been underexplored. The present study examines ChatGPT's ability to generate code solutions at different difficulty levels for introductory programming courses. We conducted an experiment where ChatGPT was tested on 127 randomly selected programming problems provided by Kattis, an automatic software grading tool for computer science programs, often used in higher education. The results showed that ChatGPT independently could solve 19 out of 127 programming tasks generated and assessed by Kattis. Further, ChatGPT was found to be able to generate accurate code solutions for simple problems but encountered difficulties with more complex programming tasks. The results contribute to the ongoing debate on the utility of AI-powered tools in programming education., Comment: 10 pages, 2 figures, 3 tables. (Pre-print). Final version to be submitted to ACM Journals. LAK2024, March,18-22, 2024, Kyoto, Japan

Existing effect measures for compositional features are inadequate for many modern applications for two reasons. First, modern datasets with compositional covariates, for example in microbiome research, display traits such as high-dimensionality and sparsity that can be poorly modelled with traditional parametric approaches. Second, assessing -- in an unbiased way -- how summary statistics of a composition (e.g., racial diversity) affect a response variable is not straightforward. In this work, we propose a framework based on hypothetical data perturbations that addresses both issues. Unlike many existing effect measures for compositional features, we do not define our effects based on a parametric model or a transformation of the data. Instead, we use perturbations to define interpretable statistical functionals on the compositions themselves, which we call average perturbation effects. These effects naturally account for confounding that biases frequently used marginal dependence analyses. We show how average perturbation effects can be estimated efficiently by deriving a perturbation-dependent reparametrization and applying semiparametric estimation techniques. We analyze the proposed estimators empirically on simulated and semi-synthetic data and demonstrate advantages over existing techniques on data from New York schools and microbiome data. For all proposed estimators, we provide confidence intervals with uniform asymptotic coverage guarantees.

Discovering causal relationships from observational data is a fundamental yet challenging task. Invariant causal prediction (ICP, Peters et al., 2016) is a method for causal feature selection which requires data from heterogeneous settings and exploits that causal models are invariant. ICP has been extended to general additive noise models and to nonparametric settings using conditional independence tests. However, the latter often suffer from low power (or poor type I error control) and additive noise models are not suitable for applications in which the response is not measured on a continuous scale, but reflects categories or counts. Here, we develop transformation-model (TRAM) based ICP, allowing for continuous, categorical, count-type, and uninformatively censored responses (these model classes, generally, do not allow for identifiability when there is no exogenous heterogeneity). As an invariance test, we propose TRAM-GCM based on the expected conditional covariance between environments and score residuals with uniform asymptotic level guarantees. For the special case of linear shift TRAMs, we also consider TRAM-Wald, which tests invariance based on the Wald statistic. We provide an open-source R package 'tramicp' and evaluate our approach on simulated data and in a case study investigating causal features of survival in critically ill patients., Comment: Code available at https://github.com/LucasKook/tramicp.git

Testing the significance of a variable or group of variables $X$ for predicting a response $Y$, given additional covariates $Z$, is a ubiquitous task in statistics. A simple but common approach is to specify a linear model, and then test whether the regression coefficient for $X$ is non-zero. However, when the model is misspecified, the test may have poor power, for example when $X$ is involved in complex interactions, or lead to many false rejections. In this work we study the problem of testing the model-free null of conditional mean independence, i.e. that the conditional mean of $Y$ given $X$ and $Z$ does not depend on $X$. We propose a simple and general framework that can leverage flexible nonparametric or machine learning methods, such as additive models or random forests, to yield both robust error control and high power. The procedure involves using these methods to perform regressions, first to estimate a form of projection of $Y$ on $X$ and $Z$ using one half of the data, and then to estimate the expected conditional covariance between this projection and $Y$ on the remaining half of the data. While the approach is general, we show that a version of our procedure using spline regression achieves what we show is the minimax optimal rate in this nonparametric testing problem. Numerical experiments demonstrate the effectiveness of our approach both in terms of maintaining Type I error control, and power, compared to several existing approaches., Comment: 97 pages, 5 figures

Confounder selection is perhaps the most important step in the design of observational studies. A number of criteria, often with different objectives and approaches, have been proposed, and their validity and practical value have been debated in the literature. Here, we provide a unified review of these criteria and the assumptions behind them. We list several objectives that confounder selection methods aim to achieve and discuss the amount of structural knowledge required by different approaches. Finally, we discuss limitations of the existing approaches and implications for practitioners., Comment: 15 pages

We study the problem of testing the null hypothesis that X and Y are conditionally independent given Z, where each of X, Y and Z may be functional random variables. This generalises testing the significance of X in a regression model of scalar response Y on functional regressors X and Z. We show however that even in the idealised setting where additionally (X, Y, Z) has a Gaussian distribution, the power of any test cannot exceed its size. Further modelling assumptions are needed and we argue that a convenient way of specifying these is based on choosing methods for regressing each of X and Y on Z. We propose a test statistic involving inner products of the resulting residuals that is simple to compute and calibrate: type I error is controlled uniformly when the in-sample prediction errors are sufficiently small. We show this requirement is met by ridge regression in functional linear model settings without requiring any eigen-spacing conditions or lower bounds on the eigenvalues of the covariance of the functional regressor. We apply our test in constructing confidence intervals for truncation points in truncated functional linear models and testing for edges in a functional graphical model for EEG data., Comment: To appear in JRSSB

The introduction of accelerator devices such as graphics processing units (GPUs) has had profound impact on molecular dynamics simulations and has enabled order-of-magnitude performance advances using commodity hardware. To fully reap these benefits, it has been necessary to reformulate some of the most fundamental algorithms, including the Verlet list, pair searching and cut-offs. Here, we present the heterogeneous parallelization and acceleration design of molecular dynamics implemented in the GROMACS codebase over the last decade. The setup involves a general cluster-based approach to pair lists and non-bonded pair interactions that utilizes both GPUs and CPU SIMD acceleration efficiently, including the ability to load-balance tasks between CPUs and GPUs. The algorithm work efficiency is tuned for each type of hardware, and to use accelerators more efficiently we introduce dual pair lists with rolling pruning updates. Combined with new direct GPU-GPU communication as well as GPU integration, this enables excellent performance from single GPU simulations through strong scaling across multiple GPUs and efficient multi-node parallelization., Comment: The following article has been submitted to the Journal of Chemical Physics

The cross sections for the charmonium production processes p pbar -> m Psi, where m is a light meson and Psi is a charmonium state, are of great interest for the planned p-pbar experiment PANDA. In this paper we estimate these cross sections using known results for the decays Psi -> m p pbar which are related to these reactions by crossing. In lieu of detailed experimental data on the decay Dalitz plots, we assume a constant amplitude as a first approximation; this implies a simple relation between the cross sections and decay widths. The single measured exclusive cross section of this type is p pbar -> pi0 J/psi, which was reported by E760 to be 130 +/- 25 pb near sqrt(s) = 3.5-3.6 GeV. In comparison, our constant amplitude estimate is about 300 pb at this energy. This suggests that our approach is useful as a simple estimate, but should be refined through detailed modeling of resonances and other energy-dependent effects in the experimental Psi -> m p pbar Dalitz plots., Comment: 6 pages, 6 figures