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Glossary

Quick reference for terminology used in CellType-Refinery documentation.


A

Anti-Marker

A marker that should NOT be expressed in a cell type. Used to penalize incorrect assignments. For example, CD45 is an anti-marker for epithelial cells.

Anti-Penalty

The score deduction applied when a cluster expresses anti-markers for a cell type. Higher anti-marker expression results in larger penalties.

Ambiguous Root

A stop reason indicating the top two root categories scored too close together (gap < root_gap_threshold). The cluster cannot be confidently assigned to a single root.

Ambiguous Siblings

A stop reason indicating children at the current hierarchy level scored too close together (gap < min_gap[level]). Assignment stops at the parent level.

Assignment Path

The sequence of nodes traversed during hierarchical descent, from root to the final assigned cell type.


B

Base Score

The fundamental score component derived from marker expression, before applying DE bonuses or penalties.

Batch Effect

Technical variation between experimental batches that can affect marker expression measurements and clustering results.


C

Cell State

A transient or activation-dependent phenotype of a cell, such as "activated," "exhausted," or "proliferating." Distinguished from cell type identity.

Cell Type

A distinct biological category of cells defined by characteristic marker expression patterns and functional properties.

Cluster

A group of cells identified by unsupervised clustering algorithms based on expression similarity.

Commonness Penalty

A score reduction applied to markers that are frequently expressed across many cell types, reducing their discriminative power.

Confidence

The minimum margin (score gap) along the entire hierarchical assignment path. Higher confidence indicates more decisive assignments. Range: 0 to ~5+.

Coverage

The fraction of a cell type's expected markers that are present in the marker panel. Coverage of 0.8 means 80% of markers are available for scoring.


D

DE Bonus

Extra score contribution for markers that appear in the cluster's top differentially expressed genes. Rank-weighted to give higher weight to top-ranked DE genes.

DE Component

The differential expression portion of the marker score. Calculated from rank-weighted DE hits with commonness penalty.

DE Hits

The count of a cell type's markers that appear in the cluster's differentially expressed gene list.

Differential Expression (DE)

Statistical comparison identifying genes with significantly different expression between a cluster and other cells.


E

Enrichment

Z-score of a cluster's marker expression compared to the global mean. Positive enrichment indicates the cluster expresses the marker more than average.

Enrichment Threshold

The minimum Z-score required for a marker to be considered enriched in a cluster.

Expression Matrix

The data structure containing gene expression values for each cell, with genes as rows and cells as columns.


F

Final Score

The composite score combining base score, DE component, and anti-penalty used for ranking cell type candidates.

Frac Markers On

The fraction of a cell type's markers that are expressed above threshold in the cluster.


G

Gap Threshold

The minimum score difference required between candidates for confident assignment. Different thresholds may apply at different hierarchy levels.

Gating

The process of checking whether a cluster meets threshold requirements to be considered for a cell type. Gates include coverage, positive fraction, enrichment, and anti-penalty checks.

Gap

The score difference between the best candidate and the runner-up at any hierarchy level. Larger gaps indicate more confident assignments.

Global Mean

The average expression of a marker across all cells in the dataset, used as reference for enrichment calculations.


H

Hard Requirements

Mandatory marker expression criteria that must be met for a cell type to be considered. Failure to meet hard requirements results in immediate exclusion.

Hierarchical Descent

The top-down traversal through the marker hierarchy, starting from root categories and descending to specific cell types.

Hierarchy Level

The depth in the marker map tree structure. Level 0 is root, with increasing levels representing more specific cell type categories.


I

Intermediate Node

A non-leaf node in the marker hierarchy that has children. Assignment may stop at intermediate nodes when children are ambiguous.


L

Leaf Node

A terminal node in the marker hierarchy with no children. Represents the most specific cell type category available.

Leaf Reached

A stop reason indicating the algorithm successfully descended to the deepest level of the hierarchy. This is the ideal outcome.


M

Marker

A gene whose expression is characteristic of a particular cell type or category.

Marker Map

The hierarchical data structure defining cell types, their relationships, and associated markers.

Marker Panel

The set of genes measured in the experiment that can be used for cell type annotation.

Mean Enrichment

Average Z-score of a cluster's expression for a cell type's markers compared to global expression.

Mean Positive Fraction

Average fraction of cells in a cluster expressing each of a cell type's markers above the Q75 threshold.

Min Gap

The minimum score difference required between the best and second-best candidates at each hierarchy level. Below this threshold, assignment stops as "ambiguous."


N

No Child Passed

A stop reason indicating none of the children at the current hierarchy level passed the gating requirements. Assignment stops at the current (parent) level.

No Root Passed

A stop reason indicating no root category passed the gating requirements. The cluster is labeled "Unassigned."

Node

An entry in the marker hierarchy representing a cell type category at any level.


O

Overclustering

Excessive subdivision of cell populations resulting in biologically redundant clusters.


P

Parent Node

The immediate ancestor of a node in the marker hierarchy. All siblings share the same parent.

Per-Cell Voting

A process that calculates cell-level scores when siblings are ambiguous. Provides evidence for refinement but does NOT override cluster-level assignments.

Positive Fraction

The fraction of cells in a cluster expressing a marker above the Q75 (75th percentile) threshold.

Positive Fraction Threshold

The minimum fraction of cells required to express a marker for the cluster to be considered positive for that marker.


Q

Q75 Threshold

The 75th percentile expression value across all cells, used as the cutoff for determining positive marker expression.


R

Rank Weight

The weight applied to DE genes based on their rank position, giving higher influence to top-ranked genes.

Refinement

The process of improving cell type assignments through subclustering, merging, or manual adjustment.

Root Category

A top-level category in the marker hierarchy (e.g., Immune, Epithelial, Stromal). All hierarchical descent begins at root level.

Root Gap Threshold

The minimum score difference required between the top two root categories for confident root assignment.

Root Hard Requirements

Mandatory marker expression requirements for root categories. For example, Immune Cells may require CD45 expression above a threshold.

Root Veto Markers

Markers that, if expressed above threshold, block assignment to a root category. For example, Pan-Cytokeratin expression may veto Immune Cells assignment.

Runner-Up

The second-highest scoring candidate at any hierarchy level. Used to calculate the gap for confidence assessment.


S

Score

The numerical value representing how well a cluster matches a cell type based on marker expression patterns.

Sibling Comparison

The principle that only cell types sharing the same parent are compared at each hierarchy level. This ensures fair comparison within biological categories.

Sibling Node

A node sharing the same parent as another node in the marker hierarchy.

Stop Reason

The explanation for why hierarchical descent stopped at a particular level. Values: leaf_reached, ambiguous_siblings, no_child_passed, no_root_passed, ambiguous_root.

Subcluster

A refinement operation that re-clusters a cluster at finer resolution to separate mixed populations.


T

Technical Marker

A marker used for quality control or batch correction rather than biological cell type identification.

Top-Down Traversal

The annotation strategy of starting at broad root categories and descending through the hierarchy to specific cell types, rather than comparing all cell types directly.

Total Score

Synonym for final score; the aggregate score used for ranking candidates.


U

Unassigned

The label given to clusters that fail to pass gating requirements for any root category.

Underclustering

Insufficient subdivision of cell populations resulting in mixed clusters containing multiple cell types.


V

Veto

The blocking of a cell type assignment due to expression of exclusionary markers.

Voting Fraction

In per-cell voting, the proportion of cells within a cluster that vote for a particular cell type.


W

Weight

A multiplier applied to marker scores to adjust their influence on final scoring. Some markers may be weighted higher due to specificity.


Z

Z-Score

A statistical measure indicating how many standard deviations a value is from the mean. Used for enrichment calculations.


See Also