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Register a new userMREC: a fast and versatile framework for aligning and matching point clouds with applications to single cell molecular data
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Comparing and aligning large datasets is a pervasive problem occurring across many different knowledge domains. We introduce and study MREC, a recursive decomposition algorithm for computing matchings between data sets. The basic idea is to partition the data, match the partitions, and then recursively match the points within each pair of identified partitions. The matching itself is done using black box matching procedures that are too expensive to run on the entire data set. Using an absolute measure of the quality of a matching, the framework supports optimization over parameters including partitioning procedures and matching algorithms. By design, MREC can be applied to extremely large data sets. We analyze the procedure to describe when we can expect it to work well and demonstrate its flexibility and power by applying it to a number of alignment problems arising in the analysis of single cell molecular data.
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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.
Spectral clustering is one of the fundamental unsupervised learning methods widely used in data analysis. Sparse spectral clustering (SSC) imposes sparsity to the spectral clustering and it improves the interpretability of the model. This paper considers a widely adopted model for SSC, which can be formulated as an optimization problem over the Stiefel manifold with nonsmooth and nonconvex objective. Such an optimization problem is very challenging to solve. Existing methods usually solve its convex relaxation or need to smooth its nonsmooth part using certain smoothing techniques. In this paper, we propose a manifold proximal linear method (ManPL) that solves the original SSC formulation. We also extend the algorithm to solve the multiple-kernel SSC problems, for which an alternating ManPL algorithm is proposed. Convergence and iteration complexity results of the proposed methods are established. We demonstrate the advantage of our proposed methods over existing methods via the single-cell RNA sequencing data analysis.
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.
Opioid overdose rates have increased in the United States over the past decade and reflect a major public health crisis. Modeling and prediction of drug and opioid hotspots, where a high percentage of events fall in a small percentage of space-time, could help better focus limited social and health services. In this work we present a spatial-temporal point process model for drug overdose clustering. The data input into the model comes from two heterogeneous sources: 1) high volume emergency medical calls for service (EMS) records containing location and time, but no information on the type of non-fatal overdose and 2) fatal overdose toxicology reports from the coroner containing location and high-dimensional information from the toxicology screen on the drugs present at the time of death. We first use non-negative matrix factorization to cluster toxicology reports into drug overdose categories and we then develop an EM algorithm for integrating the two heterogeneous data sets, where the mark corresponding to overdose category is inferred for the EMS data and the high volume EMS data is used to more accurately predict drug overdose death hotspots. We apply the algorithm to drug overdose data from Indianapolis, showing that the point process defined on the integrated data outperforms point processes that use only homogeneous EMS (AUC improvement .72 to .8) or coroner data (AUC improvement .81 to .85).We also investigate the extent to which overdoses are contagious, as a function of the type of overdose, while controlling for exogenous fluctuations in the background rate that might also contribute to clustering. We find that drug and opioid overdose deaths exhibit significant excitation, with branching ratio ranging from .72 to .98.
We introduce a simple and versatile framework for image-to-image translation. We unearth the importance of normalization layers, and provide a carefully designed two-stream generative model with newly proposed feature transformations in a coarse-to-fine fashion. This allows multi-scale semantic structure information and style representation to be effectively captured and fused by the network, permitting our method to scale to various tasks in both unsupervised and supervised settings. No additional constraints (e.g., cycle consistency) are needed, contributing to a very clean and simple method. Multi-modal image synthesis with arbitrary style control is made possible. A systematic study compares the proposed method with several state-of-the-art task-specific baselines, verifying its effectiveness in both perceptual quality and quantitative evaluations.
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