Single Cell Genomics Day2021

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Rahul satijia single cell gemomics recent advances and future directions

    1. Multimodality spanning the central dogma
      RNA+ surface protein(CITE-seq)
      RNA+ATAC(10X multiome)
      缺点：都是利用做单细胞核的ATAC，所以无法针对surface proteins.

mtscATAC/ICICLE/ASAP-seq: optimized permeabilization enables ATAC-seq on whole cells

TEA-seq：scATAC+RNA+protein

Dogma-seq:scATAC+RNA+protein: surface protein, transcriptome, accessible chromatin, mtDNA mutations

inCITE-seq: intracellualr protein + RNA

    1. Reference mapping to single-cell atlas
      symphony
      scArches
      Seurat V4
      azimuth.hubmapconsortium.org: a web application that uses an annotated reference dataset to automate the processing, analysis, and interpretation of a new single-cell RNA-seq experiment.
    1. Comparative analysis of scRNA-seq datasets
  1. changes in cell-type abundance
  2. changes in expression within a cell type
  3. how about datasets without discrete clusters

三个方法推荐
MILO
muscat
Quantifying the effect of experimental perturbations at single-cell resolution

    1. Hi-resolution spatial transcriptomics
  1. 10x Visium: low resolution
  2. SLIDE-seq: high resolution, low size
  3. SLIDE-seq2: higher sensitive
  4. DBit-seq(10um), seq-scope(< 1um),PIXEL-SEQ(< 1um), Stereo-seq( <1um)
    1. Spatial deconvolution based on scRNAseq
      核心问题
      deconvolution approaches must handle batch/platform effects

方法推荐：
cell2location （Visium）
RCDT （SLIDE-seq2）

    1. Next-generation single cell screens (Perturb-seq+)

multimodal perturb-seq: ECCITE-seq, Perturb-CITE-seq

    1. Understanding the cellualr origins of COVID-19
      ACE2/TMPRSS2 expression
      Dysfunctional myeloid cells
    1. 总结

问题：
Can we use cellrank or rna velocity to infer directions across conditions?
有变化就能映射到

Cole Trapnell: Studying development robustnewss at the whole-scale embryo scale and sin

sci-Plex: profiles cells from thousands of specimens

斑马鱼图谱： 0-96hpf， 90万细胞， 859 embryos, 85 cell types,15 time points
genetic perturbations during zebrafish development: 3.1 million cells, 812 embryos 5 timepoints, 22 perturbations18-72hpf
科学问题： how do gene circuits stabilize the developmental program?

neural crest cells to divergence cell types
tfap2a and foxd3 敲除影响神经细胞发育

用指标来衡量， % increase in CV obs/exp
mean and variable in count data are often correlated: a generalized linear model to captures the trend in mean vs variance改成a b-binomial distrubution models fits the recovered cell type count data(Gamma GLM fit).

perturbations can change the observed variance: cell number/ cell and std.dev/mean
两个基因的敲除不仅影响细胞类型的细胞数，而且还影响细胞类型的variance.

how temperature stress destablize embryonic development?

升高温度
develop faster
staging embryo using variablity in cell type frequencies

exploring variability in gene regulation across developing embryonic tisstis