Construct cis pairs

construct_cis_pairs() is a helper function to facilitate construction the cis pairs. construct_cis_pairs() returns the set of target-response pairs for which the target and response are located on the same chromosome and in close physical proximity to one another. construct_cis_pairs() is a useful pair constructor function for screens that aim to map noncoding regulatory elements (e.g., enhancers or noncoding GWAS variants) to target genes in cis. construct_cis_pairs() assumes that the columns chr, start, and stop are present in the grna_target_data_frame, giving the chromosome, start position, and end position, respectively, of the region that each gRNA targets. construct_cis_pairs() takes several arguments: sceptre_object (required) distance_threshold (optional), positive_control_pairs (optional), and response_position_data_frame (optional). By default, construct_cis_pairs() pairs each gRNA target to the set of responses on the same chromosome as that target and within distance_threshold bases of that target. (The default value of distance_threshold is 500,000 bases, or half a megabase.) The positive_control_pairs data frame optionally can be passed to construct_cis_pairs(), in which case the positive control targets (i.e., the entries within the grna_target column of positive_control_pairs) are excluded from the cis pairs. One may want to exclude these from the discovery analysis if these targets are intended for positive control purposes only. See Section 2.2.2 of the manual for more detailed information about this function.

Usage

construct_cis_pairs(
  sceptre_object,
  positive_control_pairs = data.frame(),
  distance_threshold = 500000L,
  response_position_data_frame = gene_position_data_frame_grch38
)

Arguments

sceptre_object

a sceptre_object

positive_control_pairs

(optional) a data frame with columns grna_target and response_id containing the positive control pairs; if supplied, the positive control targets are excluded from the cis pairs.

distance_threshold

(optional) target-response pairs located within distance_threshold bases of one another and on the same chromosome are included in the cis discovery set.

response_position_data_frame

(optional) a data frame with columns response_id, chr, and position giving the genomic coordinate of each response; by default response_position_data_frame is set to a data frame containing the genomic coordinate of each gene in the human genome relative to reference genome GRCh38.

Value

a data frame with columns grna_target and response_id containing the cis pairs

Examples

library(sceptredata)
data(highmoi_example_data)
data(grna_target_data_frame_highmoi)
# import data
sceptre_object <- import_data(
  response_matrix = highmoi_example_data$response_matrix,
  grna_matrix = highmoi_example_data$grna_matrix,
  grna_target_data_frame = grna_target_data_frame_highmoi,
  moi = "high",
  extra_covariates = highmoi_example_data$extra_covariates,
  response_names = highmoi_example_data$gene_names
)
positive_control_pairs <- construct_positive_control_pairs(sceptre_object)
discovery_pairs <- construct_cis_pairs(sceptre_object,
  positive_control_pairs = positive_control_pairs,
  distance_threshold = 5e6
)