Infer Spatial Lactate Signaling

Infers lactate signaling in spatial transcriptomics data with distance-weighted communication scores. Supports both direct (HCAR1) and indirect (proton-sensing GPCRs) pathways with spatial context.

inferSpatialLactateSignaling(
  object,
  max_distance = 200,
  distance_decay = "gaussian",
  sigma = 50,
  include_direct = TRUE,
  include_indirect = TRUE,
  method = "combined",
  comm_method = "geometric",
  aggregate_by = "cell_type",
  min_production = 0,
  min_sensing = 0,
  normalize = TRUE,
  verbose = TRUE
)

Arguments

object

A spatial scMetaLink object (created with createScMetaLinkFromSpatial)

max_distance

Numeric. Maximum communication distance in micrometers. Spot pairs beyond this distance are considered non-interacting. Default 200 um.

distance_decay

Character. Distance decay function:

• "gaussian": Gaussian decay exp(-d^2/(2*sigma^2)) (default)

• "exponential": Exponential decay exp(-d/sigma)

• "linear": Linear decay max(0, 1 - d/max_distance)

• "none": No distance weighting, use cell type level aggregation

sigma

Numeric. Decay parameter for gaussian/exponential (in um). Default 50 um. Literature suggests lactate has medium-range diffusion (~50-80 um).

include_direct

Logical. Include direct lactate-HCAR1 signaling. Default TRUE.

include_indirect

Logical. Include indirect lactate-H+-GPCR signaling. Default TRUE.

method

Character. Scoring method: "combined", "mean", or "proportion". Default "combined".

comm_method

Character. Communication score method: "geometric", "product", "harmonic". Default "geometric".

aggregate_by

Character. Aggregation level:

• "cell_type": Aggregate by cell type (default)

• "spot": Return spot-level scores (memory intensive)

• "both": Return both levels

min_production

Numeric. Minimum production score threshold. Default 0.

min_sensing

Numeric. Minimum sensing score threshold. Default 0.

normalize

Logical. Normalize scores. Default TRUE.

verbose

Logical. Print progress messages. Default TRUE.

Value

Updated scMetaLink object with spatial_lactate_signaling results stored in the parameters slot, containing:

spot_production

Spot-level production scores

spot_direct_sensing

Spot-level direct sensing scores

spot_indirect_sensing

Spot-level indirect sensing scores

celltype_communication

Cell type level communication (if aggregate_by includes "cell_type")

spot_communication

Spot level communication (if aggregate_by includes "spot")

parameters

Analysis parameters

Examples

# \donttest{
data(st_expr)
data(st_meta)
data(st_scalefactors)

# Create spatial object
obj <- createScMetaLinkFromSpatial(
  expression_data = st_expr,
  spatial_coords = st_meta[, c("x", "y")],
  cell_meta = st_meta,
  cell_type_column = "cell_type",
  scale_factors = st_scalefactors
)
#> Created spatial scMetaLink object with 4284 genes, 1000 spots, 6 cell types

# Run spatial lactate analysis
obj <- inferSpatialLactateSignaling(obj)
#> Inferring spatial lactate signaling...
#>   Spots: 1000
#>   Cell types: 6
#>   Distance decay: gaussian (sigma=50 um, max=200 um)
#>   Available lactate genes: 17/17
#>   Calculating spot-level expression scores...
#>   Calculating spot-level production scores...
#>   Calculating spot-level direct sensing scores...
#>   Calculating spot-level indirect sensing scores...
#>   Computing spatial distance weights...
#>   Aggregating by cell type...
#> Done!
#>   Spot production scores: 1000 spots
#>   Cell type communication: 6 x 6

# Access results
spatial_results <- obj@parameters$spatial_lactate_signaling
# }