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Mapping out the coarse-grained connectivity structures of complex manifolds Biological systems often change over time, as old cells die and new cells are created through differentiation from progenitor cells. This means that at any given time, not all cells will be at the same stage of development. In this sense, a single-cell sample could contain cells at different stages of differentiation. By analyzing the data, we can identify which cells are at which stages and build a model for their biological transitions. By quantifying the connectivity of partitions (groups, clusters) of the single-cell graph, partition-based graph abstraction (PAGA) generates a much simpler abstracted graph (PAGA graph) of partitions, in which edge weights represent confidence in the presence of connections. In this notebook, we will introduce the concept of single-cell Trajectory Analysis using PAGA (Partition-based graph abstraction) in the context of hematopoietic differentiation.

Charting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. **Tangram** can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.

scVI-tools (single-cell variational inference tools) is a package for end-to-end analysis of single-cell omics data primarily developed and maintained by the Yosef Lab at UC Berkeley. scvi-tools has two components - Interface for easy use of a range of probabilistic models for single-cell omics (e.g., scVI, scANVI, totalVI). - Tools to build new probabilistic models, which are powered by PyTorch, PyTorch Lightning, and Pyro.

In the realm of cancer research, grasping the intricacies of intratumor heterogeneity and its interplay with the immune system is paramount for deciphering treatment resistance and tumor progression. While single-cell RNA sequencing unveils diverse transcriptional programs, the challenge persists in automatically discerning malignant cells from non-malignant ones within complex datasets featuring varying coverage depths. Thus, there arises a compelling need for an automated solution to this classification conundrum. SCEVAN (De Falco et al., 2023), a variational algorithm, is designed to autonomously identify the clonal copy number substructure of tumors using single-cell data. It automatically separates malignant cells from non-malignant ones, and subsequently, groups of malignant cells are examined through an optimization-driven joint segmentation process.