ABSTRACT. Assessing gene expression with morphological context is critical to our understanding of biology and the progression of disease. Historically, it has been challenging to spatially interrogate complex heterogeneous tissues in a high-throughput manner, especially without previously generated assumptions about the genes being expressed. With Visium Spatial products researchers can now map the whole transcriptome for entire H&E- or immunofluorescently stained fresh frozen or FFPE tissue sections with morphological context. Join us to learn how Visium Spatial products from 10x Genomics can provide a comprehensive understanding of the relationships between cellular function, phenotype, interactions, and location in intact tissue sections. E Ranghini1 1 10x Genomics, Pleasanton, California, USA

ABSTRACT. Recent advances in single cell multiomics technologies such as single cell RNA-seq, single cell ATAC-seq, and spatial transcriptomics have brought enormous opportunities that enable our understanding of the molecular underpinnings of pathophysiology at a single cell resolution. However, integrative analysis across single cell multiomics domains and further incorporation of genetics information have proven challenging. I will introduce our recent efforts in single cell multiomics integration, network modeling, and eQTL analysis, present computational tools to carry out these analyses, and showcase application examples in studies of traumatic brain injury, Alzheimer’s disease, and genetic control of cell-type specific hypothalamic cell types to regulate energy homeostasis. I will also highlight the challenges and future directions of integrative systems analysis of single cell multiomics data.

Xia Yang1,2,3 1Department of Integrative Biology and Physiology, University of California, Los Angeles, USA 2Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, USA 3Brain Research Institute, University of California, Los Angles, USA

ABSTRACT. The vast complexities of biology require approaches that build a complete picture from single cells to tissues and beyond. Single cell analysis is a powerful technique to characterize complex tissue types, identify rare cell populations, uncover regulatory relationships between genes and track cell trajectories. Join us to learn how Chromium Single Cell solutions from 10x Genomics can uncover molecular insights like identifying cell-type differences based on changes in gene expression and epigenetic patterns.

E Ranghini1 1 10x Genomics, Pleasanton, California, USA

ABSTRACT. The spatial organization of the human brain is fundamentally related to its function. Spatial transcriptomic approaches quantify RNA transcripts within tissue architecture thereby retaining both anatomical and transcriptome-scale molecular information. These approaches have the power to define molecular changes associated with specific cell types or neuropathology directly in postmortem human brain tissue. We used the 10x Genomics transcriptome-wide spatially-resolved transcriptomics technology, Visium, to generate spatial maps of gene expression in the six-layered dorsolateral prefrontal cortex (DLPFC) of the adult human brain. We identified layer-enriched gene expression signatures in the DLPFC and showed differential enrichment of genes associated with neuropsychiatric disorders. We also registered new and previously published single nucleus RNA-seq (snRNA-seq) data to Visium-defined cortical layers. Using algorithms such as BayesSpace and Tangram, we also defined molecularly-distinct laminar domains in an unsupervised manner. In summary, we generate spatial maps of gene expression within the architecture of the human cortex and provide a data resource to the community (http://research.libd.org/spatialLIBD) to augment ongoing neuroscience research. We discuss new applications of spatial transcriptomics technology, current limitations, and future directions.

Leonardo Collado-Torres1, Kristen R. Maynard1,2

1The Lieber Institute for Brain Development, Baltimore, MD 21205 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205