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GDB2023-Visium_SPG_AD

 GDB2023-Visium_SPG_AD

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  1. @lcolladotor lcolladotor.github.io lcolladotor.github.io/bioc_team_ds Applying Visium Spatial Proteogenomics (Visium-SPG) to study

    Alzheimer’s Disease Leonardo Collado Torres #Visium_SPG_AD May 17th 2023 #GBD23 Slides available at speakerdeck.com/lcolladotor
  2. Visium spatial clustering works for variables with high % variance

    explained. But what about other ones? DOI: 10.1038/s41593-020-00787-0
  3. Alzheimer’s disease related neuropathology Adopted and modified from B Wang

    (2018) and the Brain from the Top to Bottom in McGill University 20 um Sang Ho Kwon Amyloid beta pTau
  4. Hypothesis Local tissue microenvironments in close proximity to AD-related neuropathology

    have distinct cellular and molecular signatures. Sang Ho Kwon
  5. AD pathology signal is too small to detect by spatially-resolved

    gene expression alone research.libd.org/Visium_SPG_AD/
  6. Visium * ~5k spots in honeycomb * gene expression per

    spot * tissue (H&E staining) Immunofluorescence (IF) * multi-channel (6) images * identifies morphological features of interest * large: might be broken in tiles Channel 1 * triangle feature Channel 2 * cloud feature Channel 6 * xyz feature Tissue (bright field image) Visium spot Channel 1 feature Channel 2 feature + Visium Spatial Proteogenomics (Visium-SPG / IF) raw data: 2 types
  7. Spot ID Gene 1 Gene 2 Gene X spot0001 0

    12 39 spot0002 4 0 27 Spot ID Gene 1 Gene 2 Gene X In Tissue # cells spot0001 0 12 39 true 3 spot0002 4 0 27 false 0 * spaceranger * Loupe Browser * VistoSeg on H&E bright field image Visium Analysis @MadhaviTippani @HeenaDivecha cell VistoSeg DOI: 10.1101/2021.08.04.452489
  8. Feature ID X center Y center type intensity feat0001 5

    102 triangle 130.4 feat0002 10 30 cloud 99.1 Max (X, Y) Min (X, Y) Area ... SPG / IF Image Analysis * segment each channel * find features Challenges: * morphological features can be quite diverse * images are large * multiple tiles +
  9. Spot ID # Triangle # Cloud % triangle % cloud

    spot0001 0 12 0 17 spot0002 4 0 27 0 Merge Visium & IF IF Spot ID Gene 1 Gene 2 Gene X In Tissue # cells spot0001 0 12 39 true 3 spot0002 4 0 27 false 0 Visium downstream * QC * analyses spatialLIBD DOI: 10.1186/s12864-022-08601-w VistoSeg DOI: 10.1101/2021.08.04.452489 Check version 2!! @MadhaviTippani
  10. bioconductor.org/packages/spatialLIBD Pardo et al, 2022 DOI 10.1186/s12864-022-08601-w Maynard, Collado-Torres, 2021

    DOI 10.1038/s41593-020-00787-0 Brenda Pardo Abby Spangler @PardoBree @abspangler Louise A. Huuki-Myers @lahuuki Check her #GDB2023 poster for more! Session 1: #7
  11. Conclusions • Visium-SPG can identify local transcriptional signatures of late-stage

    AD pathology • RNAscope FISH-IF can further explore spatial gene expression patterns of a few select features • Proof-of-concept study: our work lays the groundwork. Can now use Visium-SPG for other diseases too • Future studies are needed to produce mechanistic insights • Explore our code & data at research.libd.org/Visium_SPG_AD & download it with spatialLIBD::fetch_data() ◦ There’s lots more to explore with this data! Sang Ho Kwon Slide adapted from:
  12. Contributors for this project Investigation Data analysis Mentorship Web resources

    Sang Ho Kwon @sanghokwon17 #Visium_SPG_AD In collaboration with Slides available at speakerdeck.com /lcolladotor Download data with spatialLIBD::fetch_data() Madhavi Tippani Keri Martinowich Kristen Maynard Sowmya Parthiban Jashandeep Lobana Stephanie Hicks Stephanie Page Heena Divecha Nicholas Eagles