cleaned folder

MANIFEST.in

 include README.md
 include setup.cfg
 include jass/swagger/swagger.yaml
-recursive-include jass/static *
-recursive-include celery_files *
+recursive-include jass/models/data/ *.tsv
+recursive-include jass/static *
\ No newline at end of file

data/coef_mean_model.tsv

+	0
+k_coef_mv	0.07740334977380119
+log10_avg_distance_cor_coef_mv	-0.6999110771883902
+log10_mean_gencov_coef_mv	0.746794584985343
+avg_Neff_coef_mv	0.07289261717080556
+avg_h2_coef_mv	-0.516496395500929
+avg_perc_h2_diff_region_coef_mv	0.15727591593399

data/combination_example.tsv

+GRP1,z_GIANT_HIP z_GLG_HDL z_GLG_LDL z_MAGIC_2HGLU-ADJBMI
+GRP2,z_SPIRO-UKB_FVC z_SPIRO-UKB_FEV1 z_TAGC_ASTHMA

data/gain_results.tsv

+	traits	k	avg_distance_cor	mean_gencov	avg_Neff	avg_h2	avg_perc_h2_diff_region	log10_mean_gencov	log10_avg_distance_cor	gain
+1	['z_SPIRO-UKB_FVC', 'z_SPIRO-UKB_FEV1', 'z_TAGC_ASTHMA']	0.1	0.1731946683845993	0.0637	0.3843393026739591	0.2785193310634847	0.7976315890930669	0.8139196701681637	0.8013809378674498	0.06428524764535551
+0	['z_GIANT_HIP', 'z_GLG_HDL', 'z_GLG_LDL', 'z_MAGIC_2HGLU-ADJBMI']	0.2	0.14899001074867035	0.01535	0.12076877719858631	0.22628198390356655	0.9055326131023057	0.6573854616675169	0.7879956172999502	-0.010766494024690904

data/range_feature_gain_prediction.tsv

+	minimum_value	maximum_value
+k	2.0	12.0
+log10_avg_distance_cor	-4.675617219570908	0.20864138105896807
+log10_mean_gencov	-4.4093921991254446	-0.46117501106209624
+avg_Neff	6730.5	697828.0
+avg_h2	0.014033707225812	0.4361454950334251
+avg_perc_h2_diff_region	0.0906544694784672	0.9831222899777692

doc/source/get_predicted_gain.rst

+Compute JASS power gain from the genetic architecture of traits
+===============================================================
+
+In a recent study :cite:`suzuki2023trait`, we explore how the genetic architecture of the set of traits (heritability, genetic covariance, heritability undetected by the univariate test, ...) can be predictive of statistical power gain of the multi-trait test.
+
+
+
+We implement an additional command line tool to give access our predictive model (the **jass predict-gain** command). 
+This command allows the to score swiftly a large number of traits combinations and to focus on set of traits the most promising for multi-trait testing.
+
+To work the inittable provided to the **jass predict-gain** command must contain the genetic covariance between traits. 
+
+
+.. code-block:: shell
+
+    jass predict-gain --inittable-path inittable_curated_111_traits_20-03-2024.hdf5 --combination_path ./combination_example.tsv --gain-path predicted_gain.tsv
+
+
+The second argument (--combination_path) is a path to a file containing the set of traits to be scored.
+
+.. csv-table:: Set of traits
+  :widths: 20, 70
+  :header-rows: 1
+
+    GRP1,z_GIANT_HIP z_GLG_HDL z_GLG_LDL z_MAGIC_2HGLU-ADJBMI
+    GRP2,z_SPIRO-UKB_FVC z_SPIRO-UKB_FEV1 z_TAGC_ASTHMA
+
+When executed the command will created a report at --gain-path
+
+.. csv-table:: Predicted gain
+    :header-rows: 1
+
+    traits,k,avg_distance_cor,mean_gencov,avg_Neff,avg_h2,avg_perc_h2_diff_region,log10_mean_gencov,log10_avg_distance_cor,gain
+    ['z_SPIRO-UKB_FVC'; 'z_SPIRO-UKB_FEV1'; 'z_TAGC_ASTHMA'],0.1,0.1731946683845993,0.0637,0.3843393026739591,0.2785193310634847,0.7976315890930669,0.8139196701681637,0.8013809378674498,0.06428524764535551
+    ['z_GIANT_HIP'; 'z_GLG_HDL'; 'z_GLG_LDL'; 'z_MAGIC_2HGLU-ADJBMI'],0.2,0.14899001074867035,0.01535,0.12076877719858631,0.22628198390356655,0.9055326131023057,0.6573854616675169,0.7879956172999502,-0.010766494024690904
+
+The last column provide the predicted gain ("the higher the more promising"). Note that extrapoling on new data might give lesser performances than reported in :cite:`suzuki2023trait`.
+
+.. bibliography:: reference.bib
\ No newline at end of file

doc/source/index.rst

@@ -14,6 +14,7 @@ JASS documentation
    install
    data_import
    generating_joint_analysis
+   get_predicted_gain
    command_line_usage
    web_usage
    web_admin

doc/source/reference.bib

@@ -20,6 +20,13 @@
   publisher={Oxford University Press}
 }
 
+@article{suzuki2023trait,
+  title={Trait selection strategy in multi-trait GWAS: Boosting SNPs discoverability},
+  author={Suzuki, Yuka and M{\'e}nager, Herv{\'e} and Brancotte, Bryan and Vernet, Rapha{\"e}l and Nerin, Cyril and Boetto, Christophe and Auvergne, Antoine and Linhard, Christophe and Torchet, Rachel and Lechat, Pierre and others},
+  journal={bioRxiv},
+  year={2023},
+  publisher={Cold Spring Harbor Laboratory Preprints}
+}
 
 
 @article{Pasaniuc2014,

jass/__main__.py

@@ -21,6 +21,8 @@ from jass.models.plots import (
     create_local_plot,
     create_qq_plot,
 )
+from jass.models.gain import create_features, compute_gain
+
 from pandas import read_hdf
 
 def absolute_path_of_the_file(fileName, output_file=False):
@@ -279,6 +281,15 @@ def w_gene_annotation(args):
         gene_data_path, initTable_path, df_gene_csv_path, df_exon_csv_path
     )
 
+def w_compute_gain(args):
+    inittable_path = absolute_path_of_the_file(args.inittable_path)
+    combi_path = absolute_path_of_the_file(args.combination_path)
+    combi_path_with_gain = absolute_path_of_the_file(args.gain_path, True)
+    
+    features = create_features(inittable_path, combi_path)
+    compute_gain(features, combi_path_with_gain)
+
+
 
 def get_parser():
     parser = argparse.ArgumentParser(prog="jass")
@@ -619,6 +630,27 @@ def get_parser():
         help="Existing key are 'SumStatTab' : The results of the joint analysis by SNPs - 'PhenoList' : the meta data of analysed GWAS - 'COV' : The H0 covariance used to perform joint analysis - 'GENCOV' (If present in the initTable): The genetic covariance as computed by the LDscore. Uniquely for the worktable: 'Regions' : Results of the joint analysis summarised by LD regions (Notably Lead SNPs by regions) - 'summaryTable': a double entry table summarizing the number of significant regions by test (univariate vs joint test)",
     )
     parser_create_mp.set_defaults(func=w_extract_tsv)
+    
+    # ------- compute predicted gain -------#
+    parser_create_mp = subparsers.add_parser(
+        "predict-gain", help="Predict gain based on the genetic architecture of the set of multi-trait. To function, this command need the inittable to contain genetic covariance store under the key 'GEN_COV in the inittable'"
+    )
+    parser_create_mp.add_argument(
+        "--inittable-path",
+        required=True,
+        help="Path to the inittable",
+    )
+    parser_create_mp.add_argument(
+        "--combination-path",
+        required=True,
+        help="Path to the file storing combination to be scored",
+    )
+    parser_create_mp.add_argument(
+        "--gain-path", required=True, help="path to save predicted gain"
+    )
+
+    parser_create_mp.set_defaults(func=w_compute_gain)
+    
     return parser
 
 

jass/models/data/coef_mean_model.tsv

+	0
+k_coef_mv	0.07740334977380119
+log10_avg_distance_cor_coef_mv	-0.6999110771883902
+log10_mean_gencov_coef_mv	0.746794584985343
+avg_Neff_coef_mv	0.07289261717080556
+avg_h2_coef_mv	-0.516496395500929
+avg_perc_h2_diff_region_coef_mv	0.15727591593399

jass/models/data/range_feature_gain_prediction.tsv

+	minimum_value	maximum_value
+k	2.0	12.0
+log10_avg_distance_cor	-4.675617219570908	0.20864138105896807
+log10_mean_gencov	-4.4093921991254446	-0.46117501106209624
+avg_Neff	6730.5	697828.0
+avg_h2	0.014033707225812	0.4361454950334251
+avg_perc_h2_diff_region	0.0906544694784672	0.9831222899777692

jass/models/gain.py

+import pkg_resources
+import pandas as pd
+import numpy as np
+import os
+
+# data issued from https://doi.org/10.1101/2023.10.27.564319
+stream = pkg_resources.resource_stream(__name__, 'data/range_feature_gain_prediction.tsv')
+X_range = pd.read_csv(stream, sep="\t", index_col=0)
+
+stream = pkg_resources.resource_stream(__name__, 'data/coef_mean_model.tsv')
+model_coefficients =  pd.read_csv(stream, sep="\t", index_col=0)
+
+# Scale according to observed 
+def scale_feature(X, feature_name):
+    X_std = (X - X_range.loc[feature_name, "minimum_value"]) / ( X_range.loc[feature_name, "maximum_value"] -  X_range.loc[feature_name, "minimum_value"])
+    return X_std
+
+def preprocess_feature(df_combinations):
+    # transformation of features
+ 
+    df_combinations['log10_mean_gencov'] = np.log10(df_combinations.mean_gencov)
+    df_combinations['log10_avg_distance_cor'] = np.log10(df_combinations.avg_distance_cor)
+    for f in ["k", "log10_avg_distance_cor", "log10_mean_gencov", "avg_Neff", "avg_h2", "avg_perc_h2_diff_region"]:
+        df_combinations[f] = scale_feature(df_combinations[f], f)
+    return df_combinations
+
+def compute_gain(df_combinations, path_output):
+
+    preprocess_feature(df_combinations)
+    df_combinations["gain"] = df_combinations[["k", "log10_avg_distance_cor", "log10_mean_gencov", "avg_Neff", "avg_h2", "avg_perc_h2_diff_region"]].dot(model_coefficients["0"].values)
+    df_combinations.sort_values(by="gain", ascending=False).to_csv(path_output, sep="\t")
+
+# cov to cor
+def cov2cor(c):
+    """
+    Return a correlation matrix given a covariance matrix. 
+    : c = covariance matrix
+    """
+    D = 1 / np.sqrt(np.diag(c)) # takes the inverse of sqrt of diag.
+    return D * c * D
+
+def compute_detected_undected_h2(inittable_path): 
+
+    phenoL = pd.read_hdf(inittable_path, "PhenoList")
+    gen_cov = pd.read_hdf(inittable_path, "GEN_COV")
+    region = pd.read_hdf(inittable_path, "Regions")
+
+    combi_c = list(phenoL.index)
+    reg_start=0
+    reg_end=50
+
+    chunk_size=50
+    Nchunk = region.shape[0] // chunk_size + 1
+    start_value = 0
+    
+    zscore_threshold = 5.452
+    h2_GW = np.zeros(len(combi_c))
+
+    for chunk in range(start_value, Nchunk):
+        print(chunk)
+        binf = chunk * chunk_size
+        bsup = (chunk + 1) * chunk_size
+
+        init_extract = pd.read_hdf(inittable_path, "SumStatTab", where= "Region >= {0} and Region < {1}".format(reg_start, reg_end))
+
+        init_extract[combi_c] = init_extract[combi_c].abs()
+        max_zscore = init_extract[["Region"] + combi_c].groupby("Region").max()
+
+        Neff_term = np.ones(max_zscore.shape)
+        Neff_term = Neff_term* (1/phenoL.loc[combi_c, "Effective_sample_size"].values)
+
+        beta_2 = max_zscore.mask((max_zscore < zscore_threshold)) 
+        beta_2 = beta_2 * np.sqrt(Neff_term)
+        beta_2 = beta_2.mask( (beta_2 > 0.019))
+
+        h2_GW += (beta_2**2).sum()
+
+    h2 = np.diag(gen_cov.loc[combi_c, combi_c])
+    undetected_h2 = ((h2 - h2_GW) / h2)
+
+    phenoL["h2"] = h2
+    phenoL["h2_GW"] = h2_GW
+    phenoL["undetected_h2_perc"] = undetected_h2
+    
+    return phenoL
+
+def add_h2_to_pheno_description(inittable_path):
+    phenoL_before = pd.read_hdf(inittable_path, "PhenoList")
+    if "avg_perc_h2_diff_region" in phenoL_before.columns:    
+        phenoL = compute_detected_undected_h2(inittable_path)
+        phenoL.to_hdf(inittable_path, key="table")
+
+
+def compute_mean_cov(cov, combi_c):
+    rows, cols = np.indices(cov.loc[combi_c, combi_c].shape)
+    mean_gencov = cov.loc[combi_c, combi_c].where(rows != cols).stack().abs().mean()
+    return mean_gencov
+
+def compute_diff_cor(res_cov, gen_cov, combi_c):
+    res_cor = cov2cor(res_cov.loc[combi_c, combi_c])
+    gen_cor = cov2cor(gen_cov.loc[combi_c, combi_c])
+    rows, cols = np.indices(res_cor.loc[combi_c, combi_c].shape)
+    off_gencor = res_cor.where(rows != cols).stack()
+    off_rescor = gen_cor.where(rows != cols).stack()
+    return (off_gencor - off_rescor).abs().mean()
+
+def compute_mean_undetected_h2(phenoL, combi_c):
+    mean_h2 = np.mean(phenoL.loc[combi_c, "undetected_h2_perc"])
+    return mean_h2
+
+def compute_mean_h2(phenoL, combi_c):
+    mean_h2 = np.mean(phenoL.loc[combi_c, "h2"])
+    return mean_h2
+
+def compute_mean_Neff(phenoL, combi_c):
+    mean_neff = np.mean(phenoL.loc[combi_c, "Effective_sample_size"])
+    return mean_neff
+
+
+#beta_2_GW = beta_2_GW * (1/phenoL.loc[combi_c, "Effective_sample_size"].values)
+def create_features(inittable_path, combi_file):
+    add_h2_to_pheno_description(inittable_path)
+
+    phenoL = pd.read_hdf(inittable_path, "PhenoList")
+    gen_cov = pd.read_hdf(inittable_path, "GEN_COV")
+    res_cov = pd.read_hdf(inittable_path, "COV")
+
+    combi = pd.read_csv(combi_file, sep=",", index_col=0, names=["combi"])
+    combi = list(combi.combi.str.split(" "))
+
+    D = {'traits':[] ,'k':[], 'avg_distance_cor': [], 'mean_gencov': [], 
+        'avg_Neff':[], 'avg_h2':[], 'avg_perc_h2_diff_region':[]}
+
+    for c in combi:
+        D['traits'].append(str(c))
+        D["k"].append(len(c))
+        D["avg_distance_cor"].append(compute_diff_cor(res_cov, gen_cov, c))
+        D["mean_gencov"].append(compute_mean_cov(gen_cov, c))
+        D["avg_Neff"].append(compute_mean_Neff(phenoL, c))
+
+        D["avg_h2"].append(compute_mean_h2(phenoL, c))
+        D["avg_perc_h2_diff_region"].append(compute_mean_undetected_h2(phenoL, c))
+
+    return pd.DataFrame.from_dict(D)
+

jass/test/data_test1/COV.csv

-ID	z_DISNEY_RATATOUY	z_DISNEY_POCAHONT
-z_DISNEY_RATATOUY	2.05403006060606	0.394332909090909
-z_DISNEY_POCAHONT	0.394332909090909	1.17729254545455

jass/test/data_test1/SumStatTab.txt

-rsid	position	chr	region	Z_ratatouy	Z_pocahont
-rs1	1	1	1	0.812	-1.06
-rs2	2	1	1	2.197	0.937
-rs3	3	1	2	2.049	0.854
-rs4	1	2	3	1.632	1.461
-rs5	2	2	3	0.254	-1.413
-rs6	3	2	4	0.491	0.567
-rs7	4	2	4	-0.324	0.583
-rs8	5	2	4	-1.662	-1.307
-rs9	1	3	5	1.768	-0.54
-rs10	2	3	5	0.026	1.948
-rs11	3	3	6	1.129	0.054
-rs12	4	3	7	-2.38	0.352

jass/test/data_test1/metadata.txt

-information	content
-title	Mock dataset with disney
-description	"lorem ipsum"
-ancestry	DIS
-assembly	dSNY