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Abstract Spatial transcriptomics (ST) technologies measure gene expression at thousands of locations within a two-dimensional tissue slice, enabling the study of spatial gene expression patterns. Spatial variation in gene expression is characterized byspatial gradients, or the collection of vector fields describing the direction and magnitude in which the expression of each gene increases. However, the few existing methods that learn spatial gradients from ST data either make restrictive and unrealistic assumptions on the structure of the spatial gradients or do not accurately model discrete transcript locations/counts. We introduce SLOPER (for Score-based Learning Of Poisson-modeled Expression Rates), a generative model for learning spatial gradients (vector fields) from ST data. SLOPER models the spatial distribution of mRNA transcripts with aninhomogeneous Poisson point process (IPPP)and usesscore matchingto learn spatial gradients for each gene. SLOPER utilizes the learned spatial gradients in a novel diffusion-based sampling approach to enhance the spatial coherence and specificity of the observed gene expression measurements. We demonstrate that the spatial gradients and enhanced gene expression representations learned by SLOPER leads to more accurate identification of tissue organization, spatially variable gene modules, and continuous axes of spatial variation (isodepth) compared to existing methods. Software availabilitySLOPER is available athttps://github.com/chitra-lab/SLOPER. 

The selection of marker gene panels is critical for capturing the cellular and spatial heterogeneity in the expanding atlases of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data. Most current approaches to marker gene selection operate in a label-based framework, which is inherently limited by its dependency on predefined cell type labels or clustering results. In contrast, existing label-free methods often struggle to identify genes that characterize rare cell types or subtle spatial patterns, and they frequently fail to scale efficiently with large data sets. Here, we introduce geneCover, a label-free combinatorial method that selects an optimal panel of minimally redundant marker genes based on gene-gene correlations. Our method demonstrates excellent scalability to large data sets and identifies marker gene panels that capture distinct correlation structures across the transcriptome. This allows geneCover to distinguish cell states in various tissues of living organisms effectively, including those associated with rare or otherwise difficult-to-identify cell types. We evaluate the performance of geneCover across various scRNA-seq and spatial transcriptomics data sets, comparing it to other label-free algorithms to highlight its utility and potential in diverse biological contexts. 

Definition of cell classes across the tissues of living organisms is central in the analysis of growing atlases of single-cell RNA sequencing (scRNA-seq) data across biomedicine. Marker genes for cell classes are most often defined by differential expression (DE) methods that serially assess individual genes across landscapes of diverse cells. This serial approach has been extremely useful, but is limited because it ignores possible redundancy or complementarity across genes that can only be captured by analyzing multiple genes simultaneously. Interrogating binarized expression data, we aim to identify discriminating panels of genes that are specific to, not only enriched in, individual cell types. To efficiently explore the vast space of possible marker panels, leverage the large number of cells often sequenced, and overcome zero-inflation in scRNA-seq data, we propose viewing marker gene panel selection as a variation of the “minimal set-covering problem” in combinatorial optimization. Using scRNA-seq data from blood and brain tissue, we show that this new method, CellCover, performs as good or better than DE and other methods in defining cell-type discriminating gene panels, while reducing gene redundancy and capturing cell-class-specific signals that are distinct from those defined by DE methods. Transfer learning experiments across mouse, primate, and human data demonstrate that CellCover identifies markers of conserved cell classes in neocortical neurogenesis, as well as developmental progression in both progenitors and neurons. Exploring markers of human outer radial glia (oRG, or basal RG) across mammals, we show that transcriptomic elements of this key cell type in the expansion of the human cortex likely appeared in gliogenic precursors of the rodent before the full program emerged in neurogenic cells of the primate lineage. We have assembled the public datasets we use in this report within the NeMO Analytics multi-omic data exploration environment [1], where the expression of individual genes (NeMO: Individual genes in cortex and NeMO: Individual genes in blood) and marker gene panels (NeMO: Telley 3 CellCover Panels, NeMO: Telley 12 CellCover Panels, NeMO: Sorted Brain Cell CellCover Panels, and NeMO: Blood 34 CellCover Panels) can be freely explored without coding expertise. CellCover is available in CellCover R and CellCover Python. 

Blockchain technology has heralded a new era in digital innovation, revolutionizing our approach to designing and building distributed applications in the digital sphere. Blockchain technology operates as an immutable digital ledger, where each entry representing a digital transaction is indelible and cannot be altered once established. Initially designed as the fundamental framework for cryptocurrencies, blockchain has outgrown its original purpose, demonstrating significant potential in various industries and offering a variety of security and privacy features. Our study provides a thorough and current survey of blockchain applications, security, privacy concepts, primitives, and threat models. It stands out by concentrating on how blockchain technology intersects with emerging fields like IoT, EVs, FinTech, and healthcare systems in a single framework. To provide security and privacy features, blockchain systems employ different foundational notions and primitives while tackling diverse adversarial scenarios with various capabilities and goals. This study presents a fresh examination of the current state of applications, security and privacy notions and primitives, and threat models in blockchain systems. Additionally, this work highlights existing gaps in knowledge and outlines open questions, aiming to stimulate interest in further advancements in the field. 

Distributed denial of service (DDoS) attacks have been prevalent on the Internet for decades. Albeit various defenses, they keep growing in size, frequency, and duration. The new network paradigm, Software-defined networking (SDN), is also vulnerable to DDoS attacks. SDN uses logically centralized control, bringing the advantages in maintaining a global network view and simplifying programmability. When attacks happen, the control path between the switches and their associated controllers may become congested due to their limited capacity. However, the data plane visibility of SDN provides new opportunities to defend against DDoS attacks in the cloud computing environment. To this end, we conduct measurements to evaluate the throughput of the software control agents on some of the hardware switches when they are under attacks. Then, we design a new mechanism, calledScotch, to enable the network to scale up its capability and handle the DDoS attack traffic. In our design, the congestion works as an indicator to trigger the mitigation mechanism.Scotchelastically scales up the control plane capacity by using an Open vSwitch-based overlay.Scotchtakes advantage of both the high control plane capacity of a large number of vSwitches and the high data plane capacity of commodity physical switches to increase the SDN network scalability and resiliency under abnormal (e.g., DDoS attacks) traffic surges. We have implemented a prototype and experimentally evaluatedScotch. Our experiments in the small-scale lab environment and large-scale GENI testbed demonstrate thatScotchcan elastically scale up the control channel bandwidth upon attacks.