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Recovering Spatially-Varying Cell-Specific Gene Co-expression Networks for Single-Cell Spatial Expression Data.

ABSTRACT: Recent advances in single-cell technologies enable spatial expression profiling at the cell level, making it possible to elucidate spatial changes of cell-specific genomic features. The gene co-expression network is an important feature that encodes the gene-gene marginal dependence structure and allows for the functional annotation of highly connected genes. In this paper, we design a simple and computationally efficient two-step algorithm to recover spatially-varying cell-specific gene co-expression networks for single-cell spatial expression data. The algorithm first estimates the gene expression covariance matrix for each cell type and then leverages the spatial locations of cells to construct cell-specific networks. The second step uses expression covariance matrices estimated in step one and label information from neighboring cells as an empirical prior to obtain thresholded Bayesian posterior estimates. After completing estimates for each cell, this algorithm can further predict or interpolate gene co-expression networks on tissue positions where cells are not captured. In the simulation study, the comparison against the traditional cell-type-specific network algorithms and the cell-specific network method but without incorporating spatial information highlights the advantages of the proposed algorithm in estimation accuracy. We also applied our algorithm to real-world datasets and found some meaningful biological results. The accompanied software is available on https://github.com/jingeyu/CSSN.

SUBMITTER: Yu J

PROVIDER: S-EPMC8107398 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves (Canis lupus), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves (C. lupus) during a 21-year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time-dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time-dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual-level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long-term change was density-dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long-term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source-sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density-dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.

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Recovering Spatially-Varying Cell-Specific Gene Co-expression Networks for Single-Cell Spatial Expression Data.

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