# SQL generators for DTO input preparation. # # Every function here returns a SQL string and has no side effects, so a query # can be printed and inspected before it is run. Only io.R and the driver # execute anything. # # The work for one (binding, perturbation) pair is staged through two temp # tables so the expensive scans and the perturbation dedup happen once per pair # rather than once per output file. Both temp tables hold *unfiltered* rows plus # a `sig_ok` flag; the significance filter is applied at ranking time. That # ordering matters: the pre-refactor script computed the binding/perturbation # cross-restriction against the unfiltered frames and only then applied the # p-value cutoffs. library(glue) .DTO_BIND_TBL <- "_dto_bind" .DTO_PERT_TBL <- "_dto_pert" # SQL literal for a double, or NULL-safe passthrough. .sql_num <- function(x) format(x, scientific = FALSE, trim = TRUE) # Single-quoted SQL string literal. .sql_str <- function(x) paste0("'", gsub("'", "''", x, fixed = TRUE), "'") .dir_sql <- function(asc) if (isTRUE(asc)) "ASC NULLS LAST" else "DESC NULLS LAST" # The expression part of an ORDER BY term, so a term already named in a spec's # dedup_by is not appended to it a second time. .order_expr <- function(x) { trimws(sub("[[:space:]]+(ASC|DESC)([[:space:]]+NULLS[[:space:]]+(FIRST|LAST))?$", "", trimws(x), ignore.case = TRUE )) } #' Standardised perturbation expressions #' #' @param spec A `pert_spec()`. #' @return List with `effect` and `pvalue` SQL expressions. .pert_exprs <- function(spec) { effect <- if (is.null(spec$effect_na_fill)) { spec$effect_col } else { glue("COALESCE({spec$effect_col}, {.sql_num(spec$effect_na_fill)})") } # No p-value column means every row clears the significance gate, which is # what the original `mutate(pvalue = 0)` achieved. pvalue <- if (is.null(spec$pvalue_col)) { "0.0" } else if (is.null(spec$pvalue_na_fill)) { spec$pvalue_col } else { glue("COALESCE({spec$pvalue_col}, {.sql_num(spec$pvalue_na_fill)})") } list(effect = as.character(effect), pvalue = as.character(pvalue)) } #' SQL building the perturbation temp table for one dataset #' #' Applies the target universe, the self-target removal, the optional WT #' exclusion and NA fills, and the max-|effect| dedup that collapses multiple #' probes mapping to the same locus. #' #' @param pert_db db_name of the perturbation dataset. #' @param spec A `pert_spec()`. #' @return A `CREATE OR REPLACE TEMP TABLE` statement. dto_pert_table_sql <- function(pert_db, spec) { e <- .pert_exprs(spec) wt_clause <- if (isTRUE(spec$exclude_wt)) { # str_detect(regulator_locus_tag, "WT-", negate = TRUE) is a substring # test, not a prefix test. "AND regulator_locus_tag NOT LIKE '%WT-%'" } else { "" } # The tiebreaks after abs(effect) are load-bearing, not cosmetic. Multiple # probes for one locus routinely report the *same* effect with different # p-values -- 18,893 such groups in kemmeren alone -- and abs(effect) alone # leaves the winner up to whatever order the scan produced. Since the # surviving row then faces the `pvalue <= 0.1` gate, an arbitrary winner # means the target itself appears or disappears between runs of the same # command. Preferring the more significant probe is both deterministic and # the right reading of "keep the strongest evidence for this locus"; signed # effect is the last discriminator, after which the rows are identical in # every column carried forward and the choice cannot matter. dedup_col <- if (isTRUE(spec$dedup)) { glue( " , row_number() OVER ( PARTITION BY sample_id, target_locus_tag ORDER BY abs({e$effect}) DESC NULLS LAST, {e$pvalue} ASC NULLS LAST, {e$effect} DESC NULLS LAST ) AS _rn" ) } else { "" } dedup_where <- if (isTRUE(spec$dedup)) "WHERE _rn = 1" else "" sig_ok <- if (is.null(spec$sig_filter)) "TRUE" else spec$sig_filter glue(" CREATE OR REPLACE TEMP TABLE {.DTO_PERT_TBL} AS SELECT CAST(sample_id AS VARCHAR) AS sample_id, regulator_locus_tag, target_locus_tag, effect, pvalue, ({sig_ok}) AS sig_ok FROM ( SELECT sample_id, regulator_locus_tag, target_locus_tag, {e$effect} AS effect, {e$pvalue} AS pvalue {dedup_col} FROM {pert_db} WHERE target_locus_tag IN (SELECT locus_tag FROM dto_universe) AND regulator_locus_tag IS NOT NULL AND regulator_locus_tag <> target_locus_tag {wt_clause} ) _std {dedup_where} ") } #' SQL building the binding temp table for one dataset #' #' Most binding datasets already report one row per (sample, target). Where a #' dataset does not -- harbison_2004 carries two rows for 7,744 sample/target #' pairs -- `spec$dedup_by` names the order that decides which row survives, and #' the rest are dropped here, before anything is ranked. Deduplicating at this #' point rather than at ranking time matters: `_dto_bind` also donates the #' regulator/target scope to the perturbation side, and a target must count once. #' #' @param binding_db db_name of the binding dataset. #' @param spec A `binding_spec()`. #' @return A `CREATE OR REPLACE TEMP TABLE` statement. dto_bind_table_sql <- function(binding_db, spec) { blacklist_clause <- if (length(spec$target_blacklist)) { vals <- paste(vapply(spec$target_blacklist, .sql_str, character(1)), collapse = ", ") glue("AND target_locus_tag NOT IN ({vals})") } else { "" } # Falling back to target_locus_tag keeps output byte-identical across runs # when a dataset has no natural secondary sort. tiebreak_expr <- spec$tiebreak_col %||% "target_locus_tag" sig_ok <- if (is.null(spec$sig_filter)) "TRUE" else spec$sig_filter # The spec's own rank and tiebreak orders are appended to whatever dedup_by # asks for. Once those are exhausted the surviving candidates are identical # in every column this table carries forward, so "keep the first" is a real # answer rather than whatever the scan happened to emit first. dedup_col <- "" dedup_where <- "" if (length(spec$dedup_by)) { appended <- c( glue("{spec$rank_col} {.dir_sql(spec$rank_asc)}"), glue("{tiebreak_expr} {.dir_sql(spec$tiebreak_asc)}") ) appended <- appended[!.order_expr(appended) %in% .order_expr(spec$dedup_by)] order_by <- paste( c(spec$dedup_by, appended), collapse = ",\n " ) dedup_col <- glue(" , row_number() OVER ( PARTITION BY sample_id, target_locus_tag ORDER BY {order_by} ) AS _rn") dedup_where <- "WHERE _rn = 1" } # Self-targets are deliberately NOT removed here. The pre-refactor script # donated the binding side's regulator/target scope to the perturbation side # from the *raw* binding frame, and only dropped self-targets when building # the ranked lists. Removing them at this point would shrink the scope the # perturbation side is filtered against. glue(" CREATE OR REPLACE TEMP TABLE {.DTO_BIND_TBL} AS SELECT sample_id, regulator_locus_tag, target_locus_tag, rank_value_raw, tiebreak_value, sig_ok FROM ( SELECT CAST(sample_id AS VARCHAR) AS sample_id, regulator_locus_tag, target_locus_tag, {spec$rank_col} AS rank_value_raw, {tiebreak_expr} AS tiebreak_value, ({sig_ok}) AS sig_ok {dedup_col} FROM {binding_db} WHERE target_locus_tag IN (SELECT locus_tag FROM dto_universe) AND regulator_locus_tag IS NOT NULL {blacklist_clause} ) _std {dedup_where} ") } # The cross-restriction: binding rows are kept only for regulators and targets # the paired perturbation dataset also measured, and vice versa. Computed # against the unfiltered temp tables. .bind_scope_where <- glue( "regulator_locus_tag IN (SELECT DISTINCT regulator_locus_tag FROM {.DTO_PERT_TBL}) AND target_locus_tag IN (SELECT DISTINCT target_locus_tag FROM {.DTO_PERT_TBL})" ) .pert_scope_where <- glue( "regulator_locus_tag IN (SELECT DISTINCT regulator_locus_tag FROM {.DTO_BIND_TBL}) AND target_locus_tag IN (SELECT DISTINCT target_locus_tag FROM {.DTO_BIND_TBL})" ) #' List truncation applied after ranking #' #' DTO's cost grows with the square of the number of distinct ranks in a list, #' so capping list length is the cheapest lever on runtime. Either cap is #' applied in the *outer* query -- after the significance filter, the pair scope #' and the ranking -- so the rank values that survive are the true ranks the #' untruncated list would have had, not a renumbering of the top slice. #' #' Two policies: #' #' * `"rank"` (default) keeps whole rank blocks: `rank_value <= max_rows`. A #' list is cut to at most `max_rows` *distinct ranks*, and every row tied at #' the last surviving rank is kept, so the cut never depends on the arbitrary #' order of equals. Because `RANK()` assigns min-ranks, a list can come out #' longer than `max_rows` rows -- but the quantity DTO's runtime keys on is #' bounded at `max_rows` either way. A list with no real ordering would defeat #' the policy entirely -- every row tied at rank 1 survives whole -- so #' `dto_pert_list_sql()` never ranks on a constant column. #' * `"row"` is a hard row cap: `sort_key <= max_rows`. Never longer than #' `max_rows` rows, but the boundary can fall inside a block of tied ranks and #' keep an arbitrary subset of equals. `dto_tie_split_report()` in audit.R #' measures how often that happens for a given cap. #' #' The background is deliberately not capped under either policy: it is the #' population the test draws against and must stay the size it would be if #' nothing were truncated. #' #' @param max_rows Cap per sample, or `NULL` for no cap. #' @param truncate_by `"rank"` for whole rank blocks, `"row"` for a hard row cap. #' @return A `WHERE` clause, or `""`. .limit_where <- function(max_rows, truncate_by = c("rank", "row")) { truncate_by <- match.arg(truncate_by) if (is.null(max_rows) || !is.finite(max_rows)) { return("") } if (max_rows < 1) cli::cli_abort("{.arg max_rows} must be at least 1.") col <- if (truncate_by == "rank") "rank_value" else "sort_key" glue("WHERE {col} <= {as.integer(max_rows)}") } #' SELECT producing the binding ranked lists #' #' Ranks *after* filtering, matching the original `filter() |> mutate(rank())` #' order. #' #' Emits `sample_id, target_locus_tag, rank_value, sort_key`. `sort_key` is a #' per-sample sequence number carrying the full intended row order, including #' the tiebreak. Writers order by it rather than relying on the order rows #' happen to come out of a table, so a file's contents never depend on DuckDB's #' scan-order behaviour. #' #' The tiebreak reproduces a subtlety of the pre-refactor script: it sorted by #' descending enrichment before sorting by rank, and because `dplyr::arrange()` #' is stable, enrichment ended up breaking ties. Making that explicit also makes #' it reproducible. #' #' @param spec A `binding_spec()`. #' @param max_rows Cap per sample; see `.limit_where()`. #' @param truncate_by Truncation policy; see `.limit_where()`. #' @return A SELECT statement. dto_binding_list_sql <- function(spec, max_rows = NULL, truncate_by = c("rank", "row")) { rank_dir <- .dir_sql(spec$rank_asc) tiebreak_dir <- .dir_sql(spec$tiebreak_asc) limit_where <- .limit_where(max_rows, truncate_by) glue(" SELECT sample_id, target_locus_tag, rank_value, sort_key FROM ( SELECT sample_id, target_locus_tag, RANK() OVER ( PARTITION BY sample_id ORDER BY rank_value_raw {rank_dir} ) AS rank_value, ROW_NUMBER() OVER ( PARTITION BY sample_id ORDER BY rank_value_raw {rank_dir}, tiebreak_value {tiebreak_dir}, target_locus_tag ) AS sort_key FROM {.DTO_BIND_TBL} WHERE sig_ok AND regulator_locus_tag <> target_locus_tag AND {.bind_scope_where} ) _ranked {limit_where} ORDER BY sample_id, sort_key ") } #' SELECT producing a perturbation ranked list #' #' One query shape serves both output directories. `pr/effect/` ranks by #' descending |effect|, `pr/pvalue/` by ascending p-value; each uses the other #' quantity as its tiebreak so the row order is deterministic. #' #' Asking for `"pvalue"` on a dataset with no p-value column is an error, not a #' fallback. Its `pvalue` is a constant filled in so the significance gate #' passes; ranking on it would put every target in a single rank-1 block, which #' carries no ordering at all. Such datasets get `pr/effect/` and nothing else -- #' see `pert_has_pvalue()`. #' #' @param spec A `pert_spec()`. #' @param ranking Either `"effect"` or `"pvalue"`. #' @param max_rows Cap per sample; see `.limit_where()`. #' @param truncate_by Truncation policy; see `.limit_where()`. #' @return A SELECT statement. dto_pert_list_sql <- function(spec, ranking = c("effect", "pvalue"), max_rows = NULL, truncate_by = c("rank", "row")) { ranking <- match.arg(ranking) limit_where <- .limit_where(max_rows, truncate_by) if (ranking == "pvalue" && !pert_has_pvalue(spec)) { cli::cli_abort(c( "This dataset reports no p-value, so it has no p-value-ranked list.", i = "Its {.field pvalue} column is a constant placeholder for the significance gate.", i = "Rank by {.val effect}, or test with {.fun pert_has_pvalue} first." )) } rank_expr <- switch(ranking, effect = "abs(effect) DESC NULLS LAST", pvalue = "pvalue ASC NULLS LAST" ) tiebreak <- switch(ranking, effect = "pvalue ASC NULLS LAST", pvalue = "abs(effect) DESC NULLS LAST" ) glue(" SELECT sample_id, target_locus_tag, rank_value, sort_key FROM ( SELECT sample_id, target_locus_tag, RANK() OVER (PARTITION BY sample_id ORDER BY {rank_expr}) AS rank_value, ROW_NUMBER() OVER ( PARTITION BY sample_id ORDER BY {rank_expr}, {tiebreak}, target_locus_tag ) AS sort_key FROM {.DTO_PERT_TBL} WHERE sig_ok AND {.pert_scope_where} ) _ranked {limit_where} ORDER BY sample_id, sort_key ") } #' SELECT counting the rows of each written ranked list #' #' Wraps a list SELECT to give one row per sample. Used to drop lookup entries #' whose perturbation list is too short to produce a meaningful DTO result -- #' counting here rather than stat-ing the written files keeps the decision on the #' same query that produced them. #' #' @param list_sql A SELECT from `dto_binding_list_sql()` or `dto_pert_list_sql()`. #' @return A SELECT emitting `sample_id`, `n_targets`. dto_list_sizes_sql <- function(list_sql) { glue(" SELECT sample_id, COUNT(*) AS n_targets FROM ({list_sql}) _l GROUP BY sample_id ") } #' SELECT producing the shared background #' #' The background is every perturbation target inside the pair's scope, with no #' significance filter applied -- the population the DTO test draws against. #' It is unaffected by the ranked-list cap, by design: truncating the lists is a #' runtime optimisation and must not change the population they are scored #' against. #' #' @return A SELECT statement. dto_background_sql <- function() { glue(" SELECT DISTINCT target_locus_tag FROM {.DTO_PERT_TBL} WHERE {.pert_scope_where} ORDER BY target_locus_tag ") } #' SELECT mapping sample_id to regulator for one side of a pair #' #' Restricted to the same rows that produced ranked-list files, so the lookup #' never references a file that was not written. #' #' @param side Either `"binding"` or `"perturbation"`. #' @return A SELECT statement. dto_sample_map_sql <- function(side = c("binding", "perturbation")) { side <- match.arg(side) tbl <- if (side == "binding") .DTO_BIND_TBL else .DTO_PERT_TBL scope <- if (side == "binding") .bind_scope_where else .pert_scope_where # _dto_pert drops self-targets when it is built; _dto_bind keeps them so it # can donate an unreduced scope, so the binding side filters them here to # match the rows that produced ranked-list files. self_clause <- if (side == "binding") "AND regulator_locus_tag <> target_locus_tag" else "" glue(" SELECT DISTINCT sample_id, regulator_locus_tag FROM {tbl} WHERE sig_ok {self_clause} AND {scope} ORDER BY sample_id ") } #' SQL dropping the per-pair temp tables #' #' @return A statement dropping both temp tables. dto_drop_pair_tables_sql <- function() { glue("DROP TABLE IF EXISTS {.DTO_BIND_TBL}; DROP TABLE IF EXISTS {.DTO_PERT_TBL};") }