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Reading Single-Cell QC Metrics

Single-cell QC metrics are measurements used to assess whether a barcode represents a cell and whether that captured cell profile is usable. Their input is a raw or filtered feature-barcode matrix, and their output supports decisions to retain, review, or exclude barcodes.

This plot sorts all barcodes by total UMI.

axismeaning
xbarcode rank by UMI count
ytotal UMI per barcode, commonly on a log scale

The high-count beginning is enriched for cells, while the long low-count tail is enriched for background. A knee or inflection is a candidate boundary, not a perfect separation.

Low-RNA cell types can lie near the tail. A total-count cutoff can remove them selectively.

The sum of UMI counts across genes for one barcode reflects both library complexity and cellular RNA content.

  • Very low: empty droplet, damage, or poor capture
  • Very high: doublet or a naturally large, RNA-rich cell

Interpret extremes within each sample and with cell-type markers.

The number of genes with at least one UMI describes the diversity of detected transcripts. It is strongly related to total UMI, so view both together. High UMI with unusually few genes may indicate domination by a small set of abundant RNAs or background.

This is the fraction of all UMIs assigned to mitochondrial genes. Loss of cytoplasmic RNA from a damaged cell can increase it, but normal ranges differ by tissue and type.

Do not rely blindly on an MT- symbol prefix across species and annotations. Record the mitochondrial gene list used.

Ribosomal, haemoglobin, and stress signals

Section titled “Ribosomal, haemoglobin, and stress signals”

Ribosomal fraction, haemoglobin genes, heat-shock genes, and immediate-early genes can reveal sample condition and dissociation artifacts. They are contextual signals, not automatic row-deletion rules.

A model-based score estimates how much a row resembles two cells captured together. Scrublet simulates doublets by adding observed cells and compares them with observed neighbourhoods.

Review expected loading-related doublet rate, high UMI and gene counts, incompatible lineage markers, and doublet-enriched clusters together with the score.

RNA released from broken cells enters droplets. The expression profile of empty droplets can estimate this background and its contribution to occupied droplets.

SoupX and CellBender outputs are model estimates. Preserve matrices before and after correction, then examine marker specificity and count changes.

metricquestion
estimated cellsWere the expected cell-associated barcodes recovered?
reads per cellHow deeply was each captured cell sequenced?
sequencing saturationHow many new UMIs are likely from more sequencing?
fraction reads in cellsWhat fraction of valid reads belongs to called cells?
mapping rateHow many cDNA reads aligned to the reference?

One poor value can have several causes. Low fraction reads in cells may reflect ambient RNA, poor viability, or cell-calling settings.

  • Raw barcode and called-cell counts
  • Per-sample metric distributions
  • Lower and upper thresholds
  • Cells removed at each stage
  • Doublet and ambient-RNA tools and versions
  • Paths to matrices before and after correction
  • Review of candidate cell types preferentially removed