1
Events / Area of Influence (AoI) Hierarchy Construcon (high-dimensional space) Neighborhood Graph Embeddings and Clustering Hierarchy Exploraon (two-dimensional space) Intermediate Levels (arbitrary number) Overview Level Data Level Construction Exploration uction Constru 1 2 embedding color: marker a density heatmap color: marker c color: marker b 2 3 1 1 2 3 4 HSNE 1 HSNE 2 Cell Landmark AoI 1 2 2 3 1 1 2 3 a b c a b c 1 2 1 2 3 4 1 2 3 4 a b c AoI Density Expression Interacve Visual Analysis of Mass Cytometry Data by Hierarchical Stochasc Neighbor Embedding T Höllt 1,5 , V van Unen 3 , N Pezzo 1 , N Li 3 , M Reinders 2 , E Eisemann 1 , F Koning 3 , A Vilanova 1 , B Lelieveldt 2,4 1 Computer Graphics and Visualizaon Group, 2 Paern Recognion and Bioinformacs Group, TU Delſt, 3 Dept. of Immunohematology and Blood Transfusion, 4 Div. of Image Processing, Department of Radiology, 5 Computaonal Biology Center, LUMC, marker b marker a marker c HSNE (2 levels) HSNE 1 HSNE 1 HSNE 2 HSNE 2 AoI (# Events) Overview Level Data Level Concept: Non-Linear Hierarchy (Abstract to Single-Cell) Hierarchy Construcon and Exploraon Results ● State-of-the-art precision in a fr acon of the me Advantages References [1] van Unen, et al. Mass Cytometry of the Human Mucosal Immune System Idenfies Tissue- and Disease-Associated Immune Subsets. Immunity 44, 1227–1239 (2016). [2] Pezzo et al. Hierarchical Stochasc Neighbor Embedding. Comput. Graph. Forum 35, 21–30 (2016). [3] Höllt, et al. Cytosplore: Interacve Immune Cell Phenotyping for Large Single-Cell Datasets. Comput. Graph. Forum 35, 171–180 (2016). [4] Samusik et al. Automated mapping of phenotype space with single-cell data. Nat. Methods 13, 493–496 (2016). Acknowledgments The research leading to these results has received funding from Leiden University Medical Center, the Netherlands Organizaon for Scienfic Research (ZonMW grant 91112008) and the NWO Applied and Engineering Sciences grants 12720 (VAnPIRe) and 17721 (Genes in Space). Contact: [email protected] hp://www.cytosplore.org ● Millions(!) of cells Non-linear distances, based on single cell resoluon throughout the hierarchy Full data access, zoom into single-cell resoluon Ineracve, integrated soſtware Cytosplore [3] Introducon Immunesystem-wide CyTOF studies [1] produce millions of cells, which most computaonal tools cannot handle with- out downsampling, potenally leading to data loss. HSNE [2] builds a hierarchy of non-linear similaries, allowing exploraon of large scale datasets at full resoluon interac- vely and, through that, efficient discor- very of rare cell populaons. HSNE 1 HSNE 2 CD8+ T cells CD4+ T cells NKT & γδ T cells Eosinophils pDC CD4 + CD4 - IgD + IgM + B cells Plasma cells NK cells IgD - IgM + B cells IgD - IgM - B cells Macro phages mDCs Basophils Nonclassical monocytes Intermediate monocytes Classical monocytes GMP MPP MPP CLP CMP Branching point between classical and nonclassical pathways HSNE - 5 minutes Vortex [4] - 22 hours

Interactive Visual Analysis of Mass Cytometry Data by ... · by Hierarchical Stochastic Neighbor Embedding T Höllt 1,5 , V van Unen 3 , N Pezzotti 1 , N Li 3 , M Reinders 2 , E Eisemann

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Page 1: Interactive Visual Analysis of Mass Cytometry Data by ... · by Hierarchical Stochastic Neighbor Embedding T Höllt 1,5 , V van Unen 3 , N Pezzotti 1 , N Li 3 , M Reinders 2 , E Eisemann

Events / Area of Influence (AoI)

Hierarchy Construction (high-dimensional space)

Neighborhood Graph Embeddings and Clustering

Hierarchy Exploration (two-dimensional space)

Inte

rmed

iate

Lev

els

(arb

itrar

y nu

mbe

r)O

verv

iew

Lev

elDa

ta L

evel

Construction ExplorationConstructionConstruction

1

2

embedding

color: marker a

density

heatmap

color: marker c

color: marker b

2 3

1

1

2

3

4

HSNE 1

HSN

E 2

CellLandmarkAoI

1

2

2 3

1

1 2 3

abc

abc

1 2

1

2

34

1 2 3 4

abc

AoI

Dens

ity

Expr

essio

n

Interactive Visual Analysis of Mass Cytometry Data by Hierarchical Stochastic Neighbor Embedding

T Höllt1,5, V van Unen3, N Pezzotti1, N Li3, M Reinders2, E Eisemann1, F Koning3, A Vilanova1, B Lelieveldt2,4

1Computer Graphics and Visualization Group, 2Pattern Recognition and Bioinformatics Group, TU Delft,3Dept. of Immunohematology and Blood Transfusion, 4Div. of Image Processing, Department of Radiology,

5Computational Biology Center, LUMC,

marker b

marker a

mar

ker c

HSNE(2 levels)

HSNE 1 HSNE 1

HSN

E 2

HSN

E 2

AoI(# Events)

Overview Level Data Level

Concept: Non-Linear Hierarchy (Abstract to Single-Cell)

Hierarchy Construction and Exploration

Results● State-of-the-art precision in a fraction of the time

Advantages

References[1] van Unen, et al. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets. Immunity 44, 1227–1239 (2016).[2] Pezzotti et al. Hierarchical Stochastic Neighbor Embedding. Comput. Graph. Forum 35, 21–30 (2016).[3] Höllt, et al. Cytosplore: Interactive Immune Cell Phenotyping for Large Single-Cell Datasets. Comput. Graph. Forum 35, 171–180 (2016).[4] Samusik et al. Automated mapping of phenotype space with single-cell data. Nat. Methods 13, 493–496 (2016).

AcknowledgmentsThe research leading to these results has received funding from Leiden University Medical Center, the Netherlands Organization for Scientific Research (ZonMW grant 91112008) and the NWO Applied and Engineering Sciences grants 12720 (VAnPIRe) and 17721 (Genes in Space).

Contact: [email protected] http://www.cytosplore.org

● Millions(!) of cells● Non-linear distances, based on single cell resolution throughout the hierarchy● Full data access, zoom into single-cell resolution● Ineractive, integrated software Cytosplore[3]

IntroductionImmunesystem-wide CyTOF studies[1] produce millions of cells, which most computational tools cannot handle with-out downsampling, potentially leading to data loss.HSNE[2] builds a hierarchy of non-linear similarities, allowing exploration of large scale datasets at full resolution interac-tively and, through that, efficient discor-very of rare cell populations.

HSNE 1

HS

NE

2

CD8+T cells

CD4+T cells

NKT & γδ T cells

Eosinophils

pDCCD4+

CD4-

IgD+IgM+

B cells

Plasma cells

NK cells

IgD-IgM+

B cells

IgD-IgM-

B cells

Macrophages

mDCs

Basophils

Nonclassicalmonocytes

Intermediatemonocytes

Classicalmonocytes

GMP

MPP

MPP

CLP CMP

Branching point between classicaland nonclassical pathways

HSNE - 5 minutes Vortex[4] - 22 hours