The advent of artificial intelligence, especially the progress of deep neural networks, is expected to revolutionize genetic research and offer unprecedented potential to decode the complex relationships between genetic variants and disease phenotypes, which could mark a significant step toward improving our understanding of the disease etiology. While deep neural networks hold great promise for genetic association analysis, limited research has been focused on developing neural-network-based tests to dissect complex genotype-phenotype associations. This complexity arises from the opaque nature of neural networks and the absence of defined limiting distributions. We have previously developed a kernel-based neural network model (KNN) that synergizes the strengths of linear mixed models with conventional neural networks. KNN adopts a computationally efficient minimum norm quadratic unbiased estimator (MINQUE) algorithm and uses KNN structure to capture the complex relationship between large-scale sequencing data and a disease phenotype of interest. In the KNN framework, we introduce a MINQUE-based test to assess the joint association of genetic variants with the phenotype, which considers non-linear and non-additive effects and follows a mixture of chi-square distributions. We also construct two additional tests to evaluate and interpret linear and non-linear/non-additive genetic effects, including interaction effects. Our simulations show that our method consistently controls the type I error rate under various conditions and achieves greater power than a commonly used sequence kernel association test (SKAT), especially when involving non-linear and interaction effects. When applied to real data from the UK Biobank, our approach identified genes associated with hippocampal volume, which can be further replicated and evaluated for their role in the pathogenesis of Alzheimer's disease.

The recent development of artificial intelligence (AI) technology, especially the advance of deep neural network (DNN) technology, has revolutionized many fields. While DNN plays a central role in modern AI technology, it has been rarely used in sequencing data analysis due to challenges brought by high-dimensional sequencing data (e.g., overfitting). Moreover, due to the complexity of neural networks and their unknown limiting distributions, building association tests on neural networks for genetic association analysis remains a great challenge. To address these challenges and fill the important gap of using AI in high-dimensional sequencing data analysis, we introduce a new kernel-based neural network (KNN) test for complex association analysis of sequencing data. The test is built on our previously developed KNN framework, which uses random effects to model the overall effects of high-dimensional genetic data and adopts kernel-based neural network structures to model complex genotype-phenotype relationships. Based on KNN, a Wald-type test is then introduced to evaluate the joint association of high-dimensional genetic data with a disease phenotype of interest, considering non-linear and non-additive effects (e.g., interaction effects). Through simulations, we demonstrated that our proposed method attained higher power compared to the sequence kernel association test (SKAT), especially in the presence of non-linear and interaction effects. Finally, we apply the methods to the whole genome sequencing (WGS) dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, investigating new genes associated with the hippocampal volume change over time.

Skat is a fascinating combinatorial card game, show-casing many of the intrinsic challenges for modern AI systems such as cooperative and adversarial behaviors (among the players), randomness (in the deal), and partial knowledge (due to hidden cards). Given the larger number of tricks and higher degree of uncertainty, reinforcement learning is less effective compared to classical board games like Chess and Go. As within the game of Bridge, in Skat we have a bidding and trick-taking stage. Prior to the trick-taking and as part of the bidding process, one phase in the game is to select two skat cards, whose quality may influence subsequent playing performance drastically. This paper looks into different skat selection strategies. Besides predicting the probability of winning and other hand strength functions we propose hard expert-rules and a scoring functions based on refined skat evaluation features. Experiments emphasize the impact of the refined skat putting algorithm on the playing performance of the bots, especially for AI bidding and AI game selection.

This paper proposes \emph{knowledge-based paraonoia search} (KBPS) to find forced wins during trick-taking in the card game Skat; for some one of the most interesting card games for three players. It combines efficient partial information game-tree search with knowledge representation and reasoning. This worst-case analysis, initiated after a small number of tricks, leads to a prioritized choice of cards. We provide variants of KBPS for the declarer and the opponents, and an approximation to find a forced win against most worlds in the belief space. Replaying thousands of expert games, our evaluation indicates that the AIs with the new algorithms perform better than humans in their play, achieving an average score of over 1,000 points in the agreed standard for evaluating Skat tournaments, the extended Seeger system.

Assessing the skill level of players to predict the outcome and to rank the players in a longer series of games is of critical importance for tournament play. Besides weaknesses, like an observed continuous inflation, through a steadily increasing playing body, the ELO ranking system, named after its creator Arpad Elo, has proven to be a reliable method for calculating the relative skill levels of players in zero-sum games. The evaluation of player strength in trick-taking card games like Skat or Bridge, however, is not obvious. Firstly, these are incomplete information partially observable games with more than one player, where opponent strength should influence the scoring as it does in existing ELO systems. Secondly, they are game of both skill and chance, so that besides the playing strength the outcome of a game also depends on the deal. Last but not least, there are internationally established scoring systems, in which the players are used to be evaluated, and to which ELO should align. Based on a tournament scoring system, we propose a new ELO system for Skat to overcome these weaknesses.

After impressive successes in deterministic and fully-observable board games to significantly outclass humans, game playing research shifts towards non-deterministic and imperfect information card games, where humans are still persistently better. In this paper we devise a player that challenges human supremacy in Skat. We provide a complete player for playing selected variants of the game, with effective solutions for bidding and Skat putting, extracting knowledge from several million games. For trick play we combine expert rules with engineered tree exploration for optimal open card play. For dealing with uncertainty especially in Ouvert games we search the belief space.

Decision-making in large imperfect information games is difficult. Thanks to recent success in Poker, Counterfactual Regret Minimization (CFR) methods have been at the forefront of research in these games. However, most of the success in large games comes with the use of a forward model and powerful state abstractions. In trick-taking card games like Bridge or Skat, large information sets and an inability to advance the simulation without fully determinizing the state make forward search problematic. Furthermore, state abstractions can be especially difficult to construct because the precise holdings of each player directly impact move values. In this paper we explore learning model-free policies for Skat from human game data using deep neural networks (DNN). We produce a new state-of-the-art system for bidding and game declaration by introducing methods to a) directly vary the aggressiveness of the bidder and b) declare games based on expected value while mitigating issues with rarely observed state-action pairs. Although cardplay policies learned through imitation are slightly weaker than the current best search-based method, they run orders of magnitude faster. We also explore how these policies could be learned directly from experience in a reinforcement learning setting and discuss the value of incorporating human data for this task.

In trick-taking card games, a two-step process of state sampling and evaluation is widely used to approximate move values. While the evaluation component is vital, the accuracy of move value estimates is also fundamentally linked to how well the sampling distribution corresponds the true distribution. Despite this, recent work in trick-taking card game AI has mainly focused on improving evaluation algorithms with limited work on improving sampling. In this paper, we focus on the effect of sampling on the strength of a player and propose a novel method of sampling more realistic states given move history. In particular, we use predictions about locations of individual cards made by a deep neural network --- trained on data from human gameplay - in order to sample likely worlds for evaluation. This technique, used in conjunction with Perfect Information Monte Carlo (PIMC) search, provides a substantial increase in cardplay strength in the popular trick-taking card game of Skat.

As adversarial environments become more complex, it is increasingly crucial for agents to exploit the mistakes of weaker opponents, particularly in the context of winning tournaments and competitions.In this work, we present a simple post processing technique, which wecall Perfect Information Post-Mortem Analysis (PIPMA), that can quickly assess the playing strength of an opponent in certain classes of game environments. We apply this technique to skat, a popular German card game, and show that we can achieve substantial performance gains against not only players weaker than our program, but against stronger players as well. Most importantly, PIPMA can model the opponent after only a handful of games. To our knowledge, this makes our work the first successful example of an opponent modelling technique that can adapt its play to a particular opponent in real time in a complex game setting.

Transposition tables are a powerful tool in search domains for avoiding duplicate effort and for guiding node expansions. Traditionally, however, they have only been applicable when the current state is exactly the same as a previously explored state. We consider a generalized transposition table, whereby a similarity metric that exploits local structure is used to compare the current state with a neighbourhood of previously seen states. We illustrate this concept and forward pruning based on function approximation in the domain of Skat, and show that we can achieve speedups of 16+ over standard methods.