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Circulating HSPCs - MDS, cytopenia and normal (Fig 4)

This Shiny App allows interactive interface with the MDS and cytopenia data from our circulating HSPC study.

The data shown contains all Ultima/Illumina samples processed as part of the Fig4 analysis, except for normal samples included in Fig4 reference model. Note that some samples were excluded from results shown in the paper, e.g. due to too low number of cells.

Abstract

With aging, deviation of human blood counts from their normal range accompanies the transition from health to disease. Hematopoietic stem and progenitor cells (HSPCs) deliver life-long multi-lineage output, but their variation across healthy humans with aging, and their diagnostic utility haven’t been characterized in depth thus far. To address this, we introduce an HSPC reference model using single-cell RNA profiling of circulating CD34+ cells (cHSPCs) from 148 healthy age- and sex-diverse individuals. We characterize physiological cHSPC composition, show that age related myeloid bias is predominant in older males and define age-related transcriptional signatures in lymphoid progenitors. We demonstrate the potential of this resource in future diagnosis of myelodysplastic syndrome (MDS) from peripheral blood without bone marrow sampling, defining classes of MDS patients with abnormal lymphocyte, basophil or granulocyte progenitor frequencies. Models defining patients’ reference ranges can therefore promote clinical applications of single-cell genomics in MDS and in various other states.

Where to start

On the left sidebar you will find a list of tabs, click on the tab to open it. See below a short description of each tab.

  • QC: View QC metrics of the metacell model.
  • Manifold: View the 2d projection of the manifold
  • Genes: Compare gene expression and metadata over the metacells.
  • Markers: View a heatmap of ‘marker genes’ over the metacell model.
  • Diff expression: Compare metacells / cell types.
  • Cell types: View gene expression and metadata over cell types.
  • Samples: View donor data.

# of UMIs per metacell

Max inner-fold per metacell

# of metacells with significant inner-fold

Max inner-stdev per metacell

# of cells per metacell

Max zero-fold per metacell

# of cells with zero UMIs per gene

Type Projections

Projected correlation per metacell

Fitted genes per cell type

2D Projection

Modify colors

Gene/Gene

Select axes


Gene projections

Modify colors

Markers Heatmap

  • to

Diff. Expression

2D Projection

Cell types

Advanced Options


Plot Controls:
• Plot type affects visualization
• Faceting splits into panels
• Flip coords for long labels
• Y limits in plot sidebar

Outliers Heatmap

  • to

Vein plot

Genes Trajectory

Metacell flow

Sample types

Order by

Sample/Sample

Select axes

Sample projections

Query 2D Projection

Diff. Expression

Type Projections

Gene Observed / Projected

Gene metadata

Atlas 2D Projection

Gene Input




Find genes correlated with each input gene separately
Calculate correlations between the input genes (all correlations shown, filters disabled)
Treat genes as a module and find genes correlated with the combined expression




Correlation Heatmap

Top Correlations

Instructions



How to use:

1. Enter gene names in the text area (one per line)

2. Choose correlation mode (individual vs module)

3. Adjust parameters as needed

4. Click 'Calculate Correlations' to generate results


Visualizations will appear here after calculation.

Correlation Results


Results will appear here after calculation.