Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive deconvolution (CARD), that combines cell type–specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. CARD can also impute cell type compositions and gene expression levels at unmeasured tissue locations, enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study, and perform deconvolution without a scRNA-seq reference. Applications to four datasets including a pancreatic cancer dataset identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity, and compartmentalization of pancreatic cancer.

BackgroundDimensionality reduction is an indispensable analytic component for many areas of single-cell RNA sequencing (scRNA-seq) data analysis. Proper dimensionality reduction can allow for effective noise removal and facilitate many downstream analyses that include cell clustering and lineage reconstruction. Unfortunately, despite the critical importance of dimensionality reduction in scRNA-seq analysis and the vast number of dimensionality reduction methods developed for scRNA-seq studies, few comprehensive comparison studies have been performed to evaluate the effectiveness of different dimensionality reduction methods in scRNA-seq.ResultsWe aim to fill this critical knowledge gap by providing a comparative evaluation of a variety of commonly used dimensionality reduction methods for scRNA-seq studies. Specifically, we compare 18 different dimensionality reduction methods on 30 publicly available scRNA-seq datasets that cover a range of sequencing techniques and sample sizes. We evaluate the performance of different dimensionality reduction methods for neighborhood preserving in terms of their ability to recover features of the original expression matrix, and for cell clustering and lineage reconstruction in terms of their accuracy and robustness. We also evaluate the computational scalability of different dimensionality reduction methods by recording their computational cost.ConclusionsBased on the comprehensive evaluation results, we provide important guidelines for choosing dimensionality reduction methods for scRNA-seq data analysis. We also provide all analysis scripts used in the present study at www.xzlab.org/reproduce.html.

A quantum version of generative adversarial learning is experimentally demonstrated with a superconducting circuit.

Summary To facilitate scientific collaboration on polygenic risk scores (PRSs) research, we created an extensive PRS online repository for 35 common cancer traits integrating freely available genome-wide association studies (GWASs) summary statistics from three sources: published GWASs, the NHGRI-EBI GWAS Catalog, and UK Biobank-based GWASs. Our framework condenses these summary statistics into PRSs using various approaches such as linkage disequilibrium pruning/p value thresholding (fixed or data-adaptively optimized thresholds) and penalized, genome-wide effect size weighting. We evaluated the PRSs in two biobanks: the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort at Michigan Medicine, and the population-based UK Biobank (UKB). For each PRS construct, we provide measures on predictive performance and discrimination. Besides PRS evaluation, the Cancer-PRSweb platform features construct downloads and phenome-wide PRS association study results (PRS-PheWAS) for predictive PRSs. We expect this integrated platform to accelerate PRS-related cancer research.

We propose a generalized quantum geometric tenor to understand topological quantum phase transitions, which can be defined on the parameter space with the adiabatic evolution of a quantum many-body system. The generalized quantum geometric tenor contains two different local measurements, the non-Abelian Riemannian metric and the non-Abelian Berry curvature, which are recognized as two natural geometric characterizations for the change in the ground-state properties when the parameter of the Hamiltonian varies. Our results show the symmetry-breaking and topological quantum phase transitions can be understood as the singular behavior of the local and topological properties of the quantum geometric tenor in the thermodynamic limit.