""" This module deals with partial correlations. It is an attempt to migrate over the partial correlations feature from GeneNetwork1. """ import math from functools import reduce, partial from typing import Any, Tuple, Union, Sequence import pandas import pingouin from scipy.stats import pearsonr, spearmanr from gn3.settings import TEXTDIR from gn3.random import random_string from gn3.function_helpers import compose from gn3.data_helpers import parse_csv_line from gn3.db.traits import export_informative from gn3.db.traits import retrieve_trait_info, retrieve_trait_data from gn3.db.species import species_name, translate_to_mouse_gene_id from gn3.db.correlations import ( get_filename, fetch_all_database_data, check_for_literature_info, fetch_tissue_correlations, fetch_literature_correlations, check_symbol_for_tissue_correlation, fetch_gene_symbol_tissue_value_dict_for_trait) def control_samples(controls: Sequence[dict], sampleslist: Sequence[str]): """ Fetches data for the control traits. This migrates `web/webqtl/correlation/correlationFunction.controlStrain` in GN1, with a few modifications to the arguments passed in. PARAMETERS: controls: A map of sample names to trait data. Equivalent to the `cvals` value in the corresponding source function in GN1. sampleslist: A list of samples. Equivalent to `strainlst` in the corresponding source function in GN1 """ def __process_control__(trait_data): def __process_sample__(acc, sample): if sample in trait_data["data"].keys(): sample_item = trait_data["data"][sample] val = sample_item["value"] if val is not None: return ( acc[0] + (sample,), acc[1] + (val,), acc[2] + (sample_item["variance"],)) return acc return reduce( __process_sample__, sampleslist, (tuple(), tuple(), tuple())) return reduce( lambda acc, item: ( acc[0] + (item[0],), acc[1] + (item[1],), acc[2] + (item[2],), acc[3] + (len(item[0]),), ), [__process_control__(trait_data) for trait_data in controls], (tuple(), tuple(), tuple(), tuple())) def dictify_by_samples(samples_vals_vars: Sequence[Sequence]) -> Sequence[dict]: """ Build a sequence of dictionaries from a sequence of separate sequences of samples, values and variances. This is a partial migration of `web.webqtl.correlation.correlationFunction.fixStrains` function in GN1. This implementation extracts code that will find common use, and that will find use in more than one place. """ return tuple( { sample: {"sample_name": sample, "value": val, "variance": var} for sample, val, var in zip(*trait_line) } for trait_line in zip(*(samples_vals_vars[0:3]))) def fix_samples(primary_trait: dict, control_traits: Sequence[dict]) -> Sequence[Sequence[Any]]: """ Corrects sample_names, values and variance such that they all contain only those samples that are common to the reference trait and all control traits. This is a partial migration of the `web.webqtl.correlation.correlationFunction.fixStrain` function in GN1. """ primary_samples = tuple( present[0] for present in ((sample, all(sample in control.keys() for control in control_traits)) for sample in primary_trait.keys()) if present[1]) control_vals_vars: tuple = reduce( lambda acc, x: (acc[0] + (x[0],), acc[1] + (x[1],)), ((item["value"], item["variance"]) for sublist in [tuple(control.values()) for control in control_traits] for item in sublist), (tuple(), tuple())) return ( primary_samples, tuple(primary_trait[sample]["value"] for sample in primary_samples), control_vals_vars[0], tuple(primary_trait[sample]["variance"] for sample in primary_samples), control_vals_vars[1]) def find_identical_traits( primary_name: str, primary_value: float, control_names: Tuple[str, ...], control_values: Tuple[float, ...]) -> Tuple[str, ...]: """ Find traits that have the same value when the values are considered to 3 decimal places. This is a migration of the `web.webqtl.correlation.correlationFunction.findIdenticalTraits` function in GN1. """ def __merge_identicals__( acc: Tuple[str, ...], ident: Tuple[str, Tuple[str, ...]]) -> Tuple[str, ...]: return acc + ident[1] def __dictify_controls__(acc, control_item): ckey = tuple("{:.3f}".format(item) for item in control_item[0]) return {**acc, ckey: acc.get(ckey, tuple()) + (control_item[1],)} return (reduce(## for identical control traits __merge_identicals__, (item for item in reduce(# type: ignore[var-annotated] __dictify_controls__, zip(control_values, control_names), {}).items() if len(item[1]) > 1), tuple()) or reduce(## If no identical control traits, try primary and controls __merge_identicals__, (item for item in reduce(# type: ignore[var-annotated] __dictify_controls__, zip((primary_value,) + control_values, (primary_name,) + control_names), {}).items() if len(item[1]) > 1), tuple())) def tissue_correlation( primary_trait_values: Tuple[float, ...], target_trait_values: Tuple[float, ...], method: str) -> Tuple[float, float]: """ Compute the correlation between the primary trait values, and the values of a single target value. This migrates the `cal_tissue_corr` function embedded in the larger `web.webqtl.correlation.correlationFunction.batchCalTissueCorr` function in GeneNetwork1. """ def spearman_corr(*args): result = spearmanr(*args) return (result.correlation, result.pvalue) method_fns = {"pearson": pearsonr, "spearman": spearman_corr} assert len(primary_trait_values) == len(target_trait_values), ( "The lengths of the `primary_trait_values` and `target_trait_values` " "must be equal") assert method in method_fns.keys(), ( "Method must be one of: {}".format(",".join(method_fns.keys()))) corr, pvalue = method_fns[method](primary_trait_values, target_trait_values) return (corr, pvalue) def batch_computed_tissue_correlation( primary_trait_values: Tuple[float, ...], target_traits_dict: dict, method: str) -> Tuple[dict, dict]: """ This is a migration of the `web.webqtl.correlation.correlationFunction.batchCalTissueCorr` function in GeneNetwork1 """ def __corr__(acc, target): corr = tissue_correlation(primary_trait_values, target[1], method) return ({**acc[0], target[0]: corr[0]}, {**acc[0], target[1]: corr[1]}) return reduce(__corr__, target_traits_dict.items(), ({}, {})) def correlations_of_all_tissue_traits( primary_trait_symbol_value_dict: dict, symbol_value_dict: dict, method: str) -> Tuple[dict, dict]: """ Computes and returns the correlation of all tissue traits. This is a migration of the `web.webqtl.correlation.correlationFunction.calculateCorrOfAllTissueTrait` function in GeneNetwork1. """ primary_trait_values = tuple(primary_trait_symbol_value_dict.values())[0] return batch_computed_tissue_correlation( primary_trait_values, symbol_value_dict, method) def good_dataset_samples_indexes( samples: Tuple[str, ...], samples_from_file: Tuple[str, ...]) -> Tuple[int, ...]: """ Return the indexes of the items in `samples_from_files` that are also found in `samples`. This is a partial migration of the `web.webqtl.correlation.PartialCorrDBPage.getPartialCorrelationsFast` function in GeneNetwork1. """ return tuple(sorted( samples_from_file.index(good) for good in set(samples).intersection(set(samples_from_file)))) def partial_correlations_fast(# pylint: disable=[R0913, R0914] samples, primary_vals, control_vals, database_filename, fetched_correlations, method: str, correlation_type: str) -> Tuple[ float, Tuple[float, ...]]: """ Computes partial correlation coefficients using data from a CSV file. This is a partial migration of the `web.webqtl.correlation.PartialCorrDBPage.getPartialCorrelationsFast` function in GeneNetwork1. """ assert method in ("spearman", "pearson") with open(database_filename, "r") as dataset_file: dataset = tuple(dataset_file.readlines()) good_dataset_samples = good_dataset_samples_indexes( samples, parse_csv_line(dataset[0])[1:]) def __process_trait_names_and_values__(acc, line): trait_line = parse_csv_line(line) trait_name = trait_line[0] trait_data = trait_line[1:] if trait_name in fetched_correlations.keys(): return ( acc[0] + (trait_name,), acc[1] + tuple( trait_data[i] if i in good_dataset_samples else None for i in range(len(trait_data)))) return acc processed_trait_names_values: tuple = reduce( __process_trait_names_and_values__, dataset[1:], (tuple(), tuple())) all_target_trait_names: Tuple[str, ...] = processed_trait_names_values[0] all_target_trait_values: Tuple[float, ...] = processed_trait_names_values[1] all_correlations = compute_partial( primary_vals, control_vals, all_target_trait_names, all_target_trait_values, method) ## Line 772 to 779 in GN1 are the cause of the weird complexity in the ## return below. Once the surrounding code is successfully migrated and ## reworked, this complexity might go away, by getting rid of the ## `correlation_type` parameter return len(all_correlations), tuple( corr + ( (fetched_correlations[corr[0]],) if correlation_type == "literature" else fetched_correlations[corr[0]][0:2]) for idx, corr in enumerate(all_correlations)) def build_data_frame( xdata: Tuple[float, ...], ydata: Tuple[float, ...], zdata: Union[ Tuple[float, ...], Tuple[Tuple[float, ...], ...]]) -> pandas.DataFrame: """ Build a pandas DataFrame object from xdata, ydata and zdata """ x_y_df = pandas.DataFrame({"x": xdata, "y": ydata}) if isinstance(zdata[0], float): return x_y_df.join(pandas.DataFrame({"z": zdata})) interm_df = x_y_df.join(pandas.DataFrame( {"z{}".format(i): val for i, val in enumerate(zdata)})) if interm_df.shape[1] == 3: return interm_df.rename(columns={"z0": "z"}) return interm_df def compute_partial( primary_vals, control_vals, target_vals, target_names, method: str) -> Tuple[ Union[ Tuple[str, int, float, float, float, float], None], ...]: """ Compute the partial correlations. This is a re-implementation of the `web.webqtl.correlation.correlationFunction.determinePartialsByR` function in GeneNetwork1. This implementation reworks the child function `compute_partial` which will then be used in the place of `determinPartialsByR`. TODO: moving forward, we might need to use the multiprocessing library to speed up the computations, in case they are found to be slow. """ # replace the R code with `pingouin.partial_corr` def __compute_trait_info__(target): targ_vals = target[0] targ_name = target[1] primary = [ prim for targ, prim in zip(targ_vals, primary_vals) if targ is not None] datafrm = build_data_frame( primary, tuple(targ for targ in targ_vals if targ is not None), tuple(cont for i, cont in enumerate(control_vals) if target[i] is not None)) covariates = "z" if datafrm.shape[1] == 3 else [ col for col in datafrm.columns if col not in ("x", "y")] ppc = pingouin.partial_corr( data=datafrm, x="x", y="y", covar=covariates, method=( "pearson" if "pearson" in method.lower() else "spearman")) pc_coeff = ppc["r"][0] zero_order_corr = pingouin.corr( datafrm["x"], datafrm["y"], method=( "pearson" if "pearson" in method.lower() else "spearman")) if math.isnan(pc_coeff): return ( targ_name, len(primary), pc_coeff, 1, zero_order_corr["r"][0], zero_order_corr["p-val"][0]) return ( targ_name, len(primary), pc_coeff, (ppc["p-val"][0] if not math.isnan(ppc["p-val"][0]) else ( 0 if (abs(pc_coeff - 1) < 0.0000001) else 1)), zero_order_corr["r"][0], zero_order_corr["p-val"][0]) return tuple( __compute_trait_info__(target) for target in zip(target_vals, target_names)) def partial_correlations_normal(# pylint: disable=R0913 primary_vals, control_vals, input_trait_gene_id, trait_database, data_start_pos: int, db_type: str, method: str) -> Tuple[ float, Tuple[float, ...]]: """ Computes the correlation coefficients. This is a migration of the `web.webqtl.correlation.PartialCorrDBPage.getPartialCorrelationsNormal` function in GeneNetwork1. """ def __add_lit_and_tiss_corr__(item): if method.lower() == "sgo literature correlation": # if method is 'SGO Literature Correlation', `compute_partial` # would give us LitCorr in the [1] position return tuple(item) + trait_database[1] if method.lower() in ( "tissue correlation, pearson's r", "tissue correlation, spearman's rho"): # if method is 'Tissue Correlation, *', `compute_partial` would give # us Tissue Corr in the [1] position and Tissue Corr P Value in the # [2] position return tuple(item) + (trait_database[1], trait_database[2]) return item target_trait_names, target_trait_vals = reduce( lambda acc, item: (acc[0]+(item[0],), acc[1]+(item[data_start_pos:],)), trait_database, (tuple(), tuple())) all_correlations = compute_partial( primary_vals, control_vals, target_trait_vals, target_trait_names, method) if (input_trait_gene_id and db_type == "ProbeSet" and method.lower() in ( "sgo literature correlation", "tissue correlation, pearson's r", "tissue correlation, spearman's rho")): return ( len(trait_database), tuple( __add_lit_and_tiss_corr__(item) for idx, item in enumerate(all_correlations))) return len(trait_database), all_correlations def partial_corrs(# pylint: disable=[R0913] conn, samples, primary_vals, control_vals, return_number, species, input_trait_geneid, input_trait_symbol, tissue_probeset_freeze_id, method, dataset, database_filename): """ Compute the partial correlations, selecting the fast or normal method depending on the existence of the database text file. This is a partial migration of the `web.webqtl.correlation.PartialCorrDBPage.__init__` function in GeneNetwork1. """ if database_filename: return partial_correlations_fast( samples, primary_vals, control_vals, database_filename, ( fetch_literature_correlations( species, input_trait_geneid, dataset, return_number, conn) if "literature" in method.lower() else fetch_tissue_correlations( dataset, input_trait_symbol, tissue_probeset_freeze_id, method, return_number, conn)), method, ("literature" if method.lower() == "sgo literature correlation" else ("tissue" if "tissue" in method.lower() else "genetic"))) trait_database, data_start_pos = fetch_all_database_data( conn, species, input_trait_geneid, input_trait_symbol, samples, dataset, method, return_number, tissue_probeset_freeze_id) return partial_correlations_normal( primary_vals, control_vals, input_trait_geneid, trait_database, data_start_pos, dataset, method) def literature_correlation_by_list( conn: Any, species: str, trait_list: Tuple[dict]) -> Tuple[dict]: """ This is a migration of the `web.webqtl.correlation.CorrelationPage.getLiteratureCorrelationByList` function in GeneNetwork1. """ if any((lambda t: ( bool(t.get("tissue_corr")) and bool(t.get("tissue_p_value"))))(trait) for trait in trait_list): temporary_table_name = f"LITERATURE{random_string(8)}" query1 = ( f"CREATE TEMPORARY TABLE {temporary_table_name} " "(GeneId1 INT(12) UNSIGNED, GeneId2 INT(12) UNSIGNED PRIMARY KEY, " "value DOUBLE)") query2 = ( f"INSERT INTO {temporary_table_name}(GeneId1, GeneId2, value) " "SELECT GeneId1, GeneId2, value FROM LCorrRamin3 " "WHERE GeneId1=%(geneid)s") query3 = ( "INSERT INTO {temporary_table_name}(GeneId1, GeneId2, value) " "SELECT GeneId2, GeneId1, value FROM LCorrRamin3 " "WHERE GeneId2=%s AND GeneId1 != %(geneid)s") def __set_mouse_geneid__(trait): if trait.get("geneid"): return { **trait, "mouse_geneid": translate_to_mouse_gene_id( species, trait.get("geneid"), conn) } return {**trait, "mouse_geneid": 0} def __retrieve_lcorr__(cursor, geneids): cursor.execute( f"SELECT GeneId2, value FROM {temporary_table_name} " "WHERE GeneId2 IN %(geneids)s", geneids=geneids) return dict(cursor.fetchall()) with conn.cursor() as cursor: cursor.execute(query1) cursor.execute(query2) cursor.execute(query3) traits = tuple(__set_mouse_geneid__(trait) for trait in trait_list) lcorrs = __retrieve_lcorr__( cursor, ( trait["mouse_geneid"] for trait in traits if (trait["mouse_geneid"] != 0 and trait["mouse_geneid"].find(";") < 0))) return tuple( {**trait, "l_corr": lcorrs.get(trait["mouse_geneid"], None)} for trait in traits) return trait_list return trait_list def tissue_correlation_by_list( conn: Any, primary_trait_symbol: str, tissue_probeset_freeze_id: int, method: str, trait_list: Tuple[dict]) -> Tuple[dict]: """ This is a migration of the `web.webqtl.correlation.CorrelationPage.getTissueCorrelationByList` function in GeneNetwork1. """ def __add_tissue_corr__(trait, primary_trait_values, trait_values): result = pingouin.corr( primary_trait_values, trait_values, method=("spearman" if "spearman" in method.lower() else "pearson")) return { **trait, "tissue_corr": result["r"], "tissue_p_value": result["p-val"] } if any((lambda t: bool(t.get("l_corr")))(trait) for trait in trait_list): prim_trait_symbol_value_dict = fetch_gene_symbol_tissue_value_dict_for_trait( (primary_trait_symbol,), tissue_probeset_freeze_id, conn) if primary_trait_symbol.lower() in prim_trait_symbol_value_dict: primary_trait_value = prim_trait_symbol_value_dict[ primary_trait_symbol.lower()] gene_symbol_list = tuple( trait for trait in trait_list if "symbol" in trait.keys()) symbol_value_dict = fetch_gene_symbol_tissue_value_dict_for_trait( gene_symbol_list, tissue_probeset_freeze_id, conn) return tuple( __add_tissue_corr__( trait, primary_trait_value, symbol_value_dict[trait["symbol"].lower()]) for trait in trait_list if ("symbol" in trait and bool(trait["symbol"]) and trait["symbol"].lower() in symbol_value_dict)) return tuple({ **trait, "tissue_corr": None, "tissue_p_value": None } for trait in trait_list) return trait_list def partial_correlations_entry(# pylint: disable=[R0913, R0914, R0911] conn: Any, primary_trait_name: str, control_trait_names: Tuple[str, ...], method: str, criteria: int, target_db_name: str) -> dict: """ This is the 'ochestration' function for the partial-correlation feature. This function will dispatch the functions doing data fetches from the database (and various other places) and feed that data to the functions doing the conversions and computations. It will then return the results of all of that work. This function is doing way too much. Look into splitting out the functionality into smaller functions that do fewer things. """ threshold = 0 corr_min_informative = 4 primary_trait = retrieve_trait_info(threshold, primary_trait_name, conn) group = primary_trait["group"] primary_trait_data = retrieve_trait_data(primary_trait, conn) primary_samples, primary_values, _primary_variances = export_informative( primary_trait_data) cntrl_traits = tuple( retrieve_trait_info(threshold, trait_full_name, conn) for trait_full_name in control_trait_names) cntrl_traits_data = tuple( retrieve_trait_data(cntrl_trait, conn) for cntrl_trait in cntrl_traits) species = species_name(conn, group) (cntrl_samples, cntrl_values, _cntrl_variances, _cntrl_ns) = control_samples(cntrl_traits_data, primary_samples) common_primary_control_samples = primary_samples fixed_primary_vals = primary_values fixed_control_vals = cntrl_values if not all(cnt_smp == primary_samples for cnt_smp in cntrl_samples): (common_primary_control_samples, fixed_primary_vals, fixed_control_vals, _primary_variances, _cntrl_variances) = fix_samples(primary_trait, cntrl_traits) if len(common_primary_control_samples) < corr_min_informative: return { "status": "error", "message": ( f"Fewer than {corr_min_informative} samples data entered for " f"{group} dataset. No calculation of correlation has been " "attempted."), "error_type": "Inadequate Samples"} identical_traits_names = find_identical_traits( primary_trait_name, primary_values, control_trait_names, cntrl_values) if len(identical_traits_names) > 0: return { "status": "error", "message": ( f"{identical_traits_names[0]} and {identical_traits_names[1]} " "have the same values for the {len(fixed_primary_vals)} " "samples that will be used to compute the partial correlation " "(common for all primary and control traits). In such cases, " "partial correlation cannot be computed. Please re-select your " "traits."), "error_type": "Identical Traits"} input_trait_geneid = primary_trait.get("geneid") input_trait_symbol = primary_trait.get("symbol") input_trait_mouse_geneid = translate_to_mouse_gene_id( species, input_trait_geneid, conn) tissue_probeset_freeze_id = 1 db_type = primary_trait["db"]["dataset_type"] if db_type == "ProbeSet" and method.lower() in ( "sgo literature correlation", "tissue correlation, pearson's r", "tissue correlation, spearman's rho"): return { "status": "error", "message": ( "Wrong correlation type: It is not possible to compute the " f"{method} between your trait and data in the {target_db_name} " "database. Please try again after selecting another type of " "correlation."), "error_type": "Correlation Type"} if (method.lower() == "sgo literature correlation" and ( input_trait_geneid is None or check_for_literature_info(conn, input_trait_mouse_geneid))): return { "status": "error", "message": ( "No Literature Information: This gene does not have any " "associated Literature Information."), "error_type": "Literature Correlation"} if ( method.lower() in ( "tissue correlation, pearson's r", "tissue correlation, spearman's rho") and input_trait_symbol is None): return { "status": "error", "message": ( "No Tissue Correlation Information: This gene does not have " "any associated Tissue Correlation Information."), "error_type": "Tissue Correlation"} if ( method.lower() in ( "tissue correlation, pearson's r", "tissue correlation, spearman's rho") and check_symbol_for_tissue_correlation( conn, tissue_probeset_freeze_id, input_trait_symbol)): return { "status": "error", "message": ( "No Tissue Correlation Information: This gene does not have " "any associated Tissue Correlation Information."), "error_type": "Tissue Correlation"} database_filename = get_filename(conn, target_db_name, TEXTDIR) _total_traits, all_correlations = partial_corrs( conn, common_primary_control_samples, fixed_primary_vals, fixed_control_vals, len(fixed_primary_vals), species, input_trait_geneid, input_trait_symbol, tissue_probeset_freeze_id, method, primary_trait["db"], database_filename) def __make_sorter__(method): def __sort_6__(row): return row[6] def __sort_3__(row): return row[3] if "literature" in method.lower(): return __sort_6__ if "tissue" in method.lower(): return __sort_6__ return __sort_3__ sorted_correlations = sorted( all_correlations, key=__make_sorter__(method)) add_lit_corr_and_tiss_corr = compose( partial(literature_correlation_by_list, conn, species), partial( tissue_correlation_by_list, conn, input_trait_symbol, tissue_probeset_freeze_id, method)) trait_list = add_lit_corr_and_tiss_corr(tuple( { **retrieve_trait_info( threshold, f"{primary_trait['db']['dataset_name']}::{item[0]}", conn), "noverlap": item[1], "partial_corr": item[2], "partial_corr_p_value": item[3], "corr": item[4], "corr_p_value": item[5], "rank_order": (1 if "spearman" in method.lower() else 0), **({ "tissue_corr": item[6], "tissue_p_value": item[7]} if len(item) == 8 else {}), **({"l_corr": item[6]} if len(item) == 7 else {}) } for item in sorted_correlations[:min(criteria, len(all_correlations))])) return trait_list