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Register a new userA general kernel boosting framework integrating pathways for predictive modeling based on genomic data
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Predictive modeling based on genomic data has gained popularity in biomedical research and clinical practice by allowing researchers and clinicians to identify biomarkers and tailor treatment decisions more efficiently. Analysis incorporating pathway information can boost discovery power and better connect new findings with biological mechanisms. In this article, we propose a general framework, Pathway-based Kernel Boosting (PKB), which incorporates clinical information and prior knowledge about pathways for prediction of binary, continuous and survival outcomes. We introduce appropriate loss functions and optimization procedures for different outcome types. Our prediction algorithm incorporates pathway knowledge by constructing kernel function spaces from the pathways and use them as base learners in the boosting procedure. Through extensive simulations and case studies in drug response and cancer survival datasets, we demonstrate that PKB can substantially outperform other competing methods, better identify biological pathways related to drug response and patient survival, and provide novel insights into cancer pathogenesis and treatment response.
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For precision medicine and personalized treatment, we need to identify predictive markers of disease. We focus on Alzheimers disease (AD), where magnetic resonance imaging scans provide information about the disease status. By combining imaging with genome sequencing, we aim at identifying rare genetic markers associated with quantitative traits predicted from convolutional neural networks (CNNs), which traditionally have been derived manually by experts. Kernel-based tests are a powerful tool for associating sets of genetic variants, but how to optimally model rare genetic variants is still an open research question. We propose a generalized set of kernels that incorporate prior information from various annotations and multi-omics data. In the analysis of data from the Alzheimers Disease Neuroimaging Initiative (ADNI), we evaluate whether (i) CNNs yield precise and reliable brain traits, and (ii) the novel kernel-based tests can help to identify loci associated with AD. The results indicate that CNNs provide a fast, scalable and precise tool to derive quantitative AD traits and that new kernels integrating domain knowledge can yield higher power in association tests of very rare variants.
The recent advances in single-cell technologies have enabled us to profile genomic features at unprecedented resolution and datasets from multiple domains are available, including datasets that profile different types of genomic features and datasets that profile the same type of genomic features across different species. These datasets typically have different powers in identifying the unknown cell types through clustering, and data integration can potentially lead to a better performance of clustering algorithms. In this work, we formulate the problem in an unsupervised transfer learning framework, which utilizes knowledge learned from auxiliary dataset to improve the clustering performance of target dataset. The degree of shared information among the target and auxiliary datasets can vary, and their distributions can also be different. To address these challenges, we propose an elastic coupled co-clustering based transfer learning algorithm, by elastically propagating clustering knowledge obtained from the auxiliary dataset to the target dataset. Implementation on single-cell genomic datasets shows that our algorithm greatly improves clustering performance over the traditional learning algorithms. The source code and data sets are available at https://github.com/cuhklinlab/elasticC3.
Residual Networks (ResNets) have become state-of-the-art models in deep learning and several theoretical studies have been devoted to understanding why ResNet works so well. One attractive viewpoint on ResNet is that it is optimizing the risk in a functional space by combining an ensemble of effective features. In this paper, we adopt this viewpoint to construct a new gradient boosting method, which is known to be very powerful in data analysis. To do so, we formalize the gradient boosting perspective of ResNet mathematically using the notion of functional gradients and propose a new method called ResFGB for classification tasks by leveraging ResNet perception. Two types of generalization guarantees are provided from the optimization perspective: one is the margin bound and the other is the expected risk bound by the sample-splitting technique. Experimental results show superior performance of the proposed method over state-of-the-art methods such as LightGBM.
The stochastic multi-armed bandit (MAB) problem is a common model for sequential decision problems. In the standard setup, a decision maker has to choose at every instant between several competing arms, each of them provides a scalar random variable, referred to as a reward. Nearly all research on this topic considers the total cumulative reward as the criterion of interest. This work focuses on other natural objectives that cannot be cast as a sum over rewards, but rather more involved functions of the reward stream. Unlike the case of cumulative criteria, in the problems we study here the oracle policy, that knows the problem parameters a priori and is used to center the regret, is not trivial. We provide a systematic approach to such problems, and derive general conditions under which the oracle policy is sufficiently tractable to facilitate the design of optimism-based (upper confidence bound) learning policies. These conditions elucidate an interesting interplay between the arm reward distributions and the performance metric. Our main findings are illustrated for several commonly used objectives such as conditional value-at-risk, mean-variance trade-offs, Sharpe-ratio, and more.
In this work, we consider the problem of deriving and incorporating accurate dynamic models for model predictive control (MPC) with an application to quadrotor control. MPC relies on precise dynamic models to achieve the desired closed-loop performance. However, the presence of uncertainties in complex systems and the environments they operate in poses a challenge in obtaining sufficiently accurate representations of the system dynamics. In this work, we make use of a deep learning tool, knowledge-based neural ordinary differential equations (KNODE), to augment a model obtained from first principles. The resulting hybrid model encompasses both a nominal first-principle model and a neural network learnt from simulated or real-world experimental data. Using a quadrotor, we benchmark our hybrid model against a state-of-the-art Gaussian Process (GP) model and show that the hybrid model provides more accurate predictions of the quadrotor dynamics and is able to generalize beyond the training data. To improve closed-loop performance, the hybrid model is integrated into a novel MPC framework, known as KNODE-MPC. Results show that the integrated framework achieves 73% improvement in simulations and more than 14% in physical experiments, in terms of trajectory tracking performance.
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