First cut on Kim 2014 benchmark script

downloads-generation/models_class1_kim_benchmark/GENERATE.sh

+#!/bin/bash
+#
+set -x
+
+DOWNLOAD_NAME=models_class1_kim_benchmark
+SCRATCH_DIR=${TMPDIR-/tmp}/mhcflurry-downloads-generation
+SCRIPT_ABSOLUTE_PATH="$(cd "$(dirname "${BASH_SOURCE[0]}")" && pwd)/$(basename "${BASH_SOURCE[0]}")"
+SCRIPT_DIR=$(dirname "$SCRIPT_ABSOLUTE_PATH")
+export PYTHONUNBUFFERED=1
+
+mkdir -p "$SCRATCH_DIR"
+rm -rf "$SCRATCH_DIR/$DOWNLOAD_NAME"
+mkdir "$SCRATCH_DIR/$DOWNLOAD_NAME"
+
+# Send stdout and stderr to a logfile included with the archive.
+exec >  >(tee -ia "$SCRATCH_DIR/$DOWNLOAD_NAME/LOG.txt")
+exec 2> >(tee -ia "$SCRATCH_DIR/$DOWNLOAD_NAME/LOG.txt" >&2)
+
+# Log some environment info
+date
+pip freeze
+git status
+
+cd $SCRATCH_DIR/$DOWNLOAD_NAME
+
+cp $SCRIPT_DIR/curate.py .
+cp $SCRIPT_DIR/write_validation_data.py .
+
+time python curate.py \
+    --data-kim2014 \
+        "$(mhcflurry-downloads path data_published)/bdata.2009.mhci.public.1.txt" \
+    --out-csv train.csv
+
+bzip2 train.csv
+
+mkdir models
+cp $SCRIPT_DIR/class1_pseudosequences.csv .
+python $SCRIPT_DIR/generate_hyperparameters.py > hyperparameters.yaml
+
+GPUS=$(nvidia-smi -L 2> /dev/null | wc -l) || GPUS=0
+echo "Detected GPUS: $GPUS"
+
+PROCESSORS=$(getconf _NPROCESSORS_ONLN)
+echo "Detected processors: $PROCESSORS"
+
+time mhcflurry-class1-train-allele-specific-models \
+    --data "train.csv.bz2" \
+    --allele-sequences class1_pseudosequences.csv \
+    --hyperparameters hyperparameters.yaml \
+    --out-models-dir models \
+    --held-out-fraction-reciprocal 10 \
+    --min-measurements-per-allele 20 \
+    --num-jobs $(expr $PROCESSORS \* 2) --gpus $GPUS --max-workers-per-gpu 2 --max-tasks-per-worker 50
+
+time python ./write_validation_data.py \
+    --include "train.csv.bz2" \
+    --exclude "models/train_data.csv.bz2" \
+    --only-alleles-present-in-exclude \
+    --out-data test.csv \
+    --out-summary test.summary.csv
+
+wc -l test.csv
+
+mkdir selected-models
+time mhcflurry-class1-select-allele-specific-models \
+    --data test.csv \
+    --models-dir models \
+    --out-models-dir selected-models \
+    --scoring combined:mse,consensus \
+    --consensus-num-peptides-per-length 10000 \
+    --combined-min-models 8 \
+    --combined-max-models 16 \
+    --num-jobs $(expr $PROCESSORS \* 2) --gpus $GPUS --max-workers-per-gpu 2 --max-tasks-per-worker 5
+
+time mhcflurry-calibrate-percentile-ranks \
+    --models-dir selected-models \
+    --num-peptides-per-length 100000 \
+    --num-jobs $(expr $PROCESSORS \* 2) --gpus $GPUS --max-workers-per-gpu 2 --max-tasks-per-worker 50
+
+cp $SCRIPT_ABSOLUTE_PATH .
+bzip2 LOG.txt
+tar -cjf "../${DOWNLOAD_NAME}.tar.bz2" *
+
+echo "Created archive: $SCRATCH_DIR/$DOWNLOAD_NAME.tar.bz2"

downloads-generation/models_class1_kim_benchmark/curate.py

+"""
+Filter and combine various peptide/MHC datasets to derive a composite training set,
+optionally including eluted peptides identified by mass-spec.
+"""
+import sys
+import argparse
+
+import pandas
+
+import mhcnames
+
+
+def normalize_allele_name(s):
+    try:
+        return mhcnames.normalize_allele_name(s)
+    except Exception:
+        try:
+            (a,b,c) = s.split("-")
+            return mhcnames.normalize_allele_name(
+                "%s-%s*%s" % (a,b,c))
+        except Exception:
+            return "UNKNOWN"
+
+
+parser = argparse.ArgumentParser(usage=__doc__)
+
+parser.add_argument(
+    "--data-kim2014",
+    action="append",
+    default=[],
+    help="Path to Kim 2014-style affinity data")
+parser.add_argument(
+    "--data-iedb",
+    action="append",
+    default=[],
+    help="Path to IEDB-style affinity data (e.g. mhc_ligand_full.csv)")
+parser.add_argument(
+    "--data-systemhc-atlas",
+    action="append",
+    default=[],
+    help="Path to systemhc-atlas-style mass-spec data")
+parser.add_argument(
+    "--data-abelin-mass-spec",
+    action="append",
+    default=[],
+    help="Path to Abelin Immunity 2017 mass-spec hits")
+parser.add_argument(
+    "--include-iedb-mass-spec",
+    action="store_true",
+    default=False,
+    help="Include mass-spec observations in IEDB")
+
+parser.add_argument(
+    "--out-csv",
+    required=True,
+    help="Result file")
+
+QUALITATIVE_TO_AFFINITY_AND_INEQUALITY = {
+    "Negative": (5000.0, ">"),
+    "Positive": (500.0, "<"),  # used for mass-spec hits
+    "Positive-High": (100.0, "<"),
+    "Positive-Intermediate": (1000.0, "<"),
+    "Positive-Low": (5000.0, "<"),
+}
+QUALITATIVE_TO_AFFINITY = dict(
+    (key, value[0]) for (key, value)
+    in QUALITATIVE_TO_AFFINITY_AND_INEQUALITY.items())
+QUALITATIVE_TO_INEQUALITY = dict(
+    (key, value[1]) for (key, value)
+    in QUALITATIVE_TO_AFFINITY_AND_INEQUALITY.items())
+
+
+EXCLUDE_IEDB_ALLELES = [
+    "HLA class I",
+    "HLA class II",
+]
+
+
+def load_data_kim2014(filename):
+    df = pandas.read_table(filename)
+    print("Loaded kim2014 data: %s" % str(df.shape))
+    df["measurement_source"] = "kim2014"
+    df["measurement_value"] = df.meas
+    df["measurement_type"] = (df.inequality == "=").map({
+        True: "quantitative",
+        False: "qualitative",
+    })
+    df["measurement_inequality"] = df.inequality
+    df["original_allele"] = df.mhc
+    df["peptide"] = df.sequence
+    df["allele"] = df.mhc.map(normalize_allele_name)
+    print("Dropping un-parseable alleles: %s" % ", ".join(
+        df.ix[df.allele == "UNKNOWN"]["mhc"].unique()))
+    df = df.ix[df.allele != "UNKNOWN"]
+
+    print("Loaded kim2014 data: %s" % str(df.shape))
+    return df
+
+
+def load_data_systemhc_atlas(filename, min_probability=0.99):
+    df = pandas.read_csv(filename)
+    print("Loaded systemhc atlas data: %s" % str(df.shape))
+
+    df["measurement_source"] = "systemhc-atlas"
+    df["measurement_value"] = QUALITATIVE_TO_AFFINITY["Positive"]
+    df["measurement_inequality"] = "<"
+    df["measurement_type"] = "qualitative"
+    df["original_allele"] = df.top_allele
+    df["peptide"] = df.search_hit
+    df["allele"] = df.top_allele.map(normalize_allele_name)
+
+    print("Dropping un-parseable alleles: %s" % ", ".join(
+        str(x) for x in df.ix[df.allele == "UNKNOWN"]["top_allele"].unique()))
+    df = df.loc[df.allele != "UNKNOWN"]
+    print("Systemhc atlas data now: %s" % str(df.shape))
+
+    print("Dropping data points with probability < %f" % min_probability)
+    df = df.loc[df.prob >= min_probability]
+    print("Systemhc atlas data now: %s" % str(df.shape))
+
+    print("Removing duplicates")
+    df = df.drop_duplicates(["allele", "peptide"])
+    print("Systemhc atlas data now: %s" % str(df.shape))
+
+    return df
+
+
+def load_data_abelin_mass_spec(filename):
+    df = pandas.read_csv(filename)
+    print("Loaded Abelin mass-spec data: %s" % str(df.shape))
+
+    df["measurement_source"] = "abelin-mass-spec"
+    df["measurement_value"] = QUALITATIVE_TO_AFFINITY["Positive"]
+    df["measurement_inequality"] = "<"
+    df["measurement_type"] = "qualitative"
+    df["original_allele"] = df.allele
+    df["allele"] = df.original_allele.map(normalize_allele_name)
+
+    print("Dropping un-parseable alleles: %s" % ", ".join(
+        str(x) for x in df.ix[df.allele == "UNKNOWN"]["allele"].unique()))
+    df = df.loc[df.allele != "UNKNOWN"]
+    print("Abelin mass-spec data now: %s" % str(df.shape))
+
+    print("Removing duplicates")
+    df = df.drop_duplicates(["allele", "peptide"])
+    print("Abelin mass-spec data now: %s" % str(df.shape))
+
+    return df
+
+
+def load_data_iedb(iedb_csv, include_qualitative=True, include_mass_spec=False):
+    iedb_df = pandas.read_csv(iedb_csv, skiprows=1, low_memory=False)
+    print("Loaded iedb data: %s" % str(iedb_df.shape))
+
+    print("Selecting only class I")
+    iedb_df = iedb_df.ix[
+        iedb_df["MHC allele class"].str.strip().str.upper() == "I"
+    ]
+    print("New shape: %s" % str(iedb_df.shape))
+
+    print("Dropping known unusuable alleles")
+    iedb_df = iedb_df.ix[
+        ~iedb_df["Allele Name"].isin(EXCLUDE_IEDB_ALLELES)
+    ]
+    iedb_df = iedb_df.ix[
+        (~iedb_df["Allele Name"].str.contains("mutant")) &
+        (~iedb_df["Allele Name"].str.contains("CD1"))
+    ]
+
+    iedb_df["allele"] = iedb_df["Allele Name"].map(normalize_allele_name)
+    print("Dropping un-parseable alleles: %s" % ", ".join(
+        iedb_df.ix[iedb_df.allele == "UNKNOWN"]["Allele Name"].unique()))
+    iedb_df = iedb_df.ix[iedb_df.allele != "UNKNOWN"]
+
+    print("IEDB measurements per allele:\n%s" % iedb_df.allele.value_counts())
+
+    quantitative = iedb_df.ix[iedb_df["Units"] == "nM"].copy()
+    quantitative["measurement_type"] = "quantitative"
+    quantitative["measurement_inequality"] = "="
+    print("Quantitative measurements: %d" % len(quantitative))
+
+    qualitative = iedb_df.ix[iedb_df["Units"] != "nM"].copy()
+    qualitative["measurement_type"] = "qualitative"
+    print("Qualitative measurements: %d" % len(qualitative))
+    if not include_mass_spec:
+        qualitative = qualitative.ix[
+            (~qualitative["Method/Technique"].str.contains("mass spec"))
+        ].copy()
+
+    qualitative["Quantitative measurement"] = (
+        qualitative["Qualitative Measure"].map(QUALITATIVE_TO_AFFINITY))
+    qualitative["measurement_inequality"] = (
+        qualitative["Qualitative Measure"].map(QUALITATIVE_TO_INEQUALITY))
+
+    print("Qualitative measurements (possibly after dropping MS): %d" % (
+        len(qualitative)))
+
+    iedb_df = pandas.concat(
+        (
+            ([quantitative]) +
+            ([qualitative] if include_qualitative else [])),
+        ignore_index=True)
+
+    print("IEDB measurements per allele:\n%s" % iedb_df.allele.value_counts())
+
+    print("Subselecting to valid peptides. Starting with: %d" % len(iedb_df))
+    iedb_df["Description"] = iedb_df.Description.str.strip()
+    iedb_df = iedb_df.ix[
+        iedb_df.Description.str.match("^[ACDEFGHIKLMNPQRSTVWY]+$")
+    ]
+    print("Now: %d" % len(iedb_df))
+
+    print("Annotating last author and category")
+    iedb_df["last_author"] = iedb_df.Authors.map(
+        lambda x: (
+            x.split(";")[-1]
+            .split(",")[-1]
+            .split(" ")[-1]
+            .strip()
+            .replace("*", ""))).values
+    iedb_df["category"] = (
+        iedb_df["last_author"] + " - " + iedb_df["Method/Technique"]).values
+
+    train_data = pandas.DataFrame()
+    train_data["peptide"] = iedb_df.Description.values
+    train_data["measurement_value"] = iedb_df[
+        "Quantitative measurement"
+    ].values
+    train_data["measurement_source"] = iedb_df.category.values
+    train_data["measurement_inequality"] = iedb_df.measurement_inequality.values
+
+    train_data["allele"] = iedb_df["allele"].values
+    train_data["original_allele"] = iedb_df["Allele Name"].values
+    train_data["measurement_type"] = iedb_df["measurement_type"].values
+    train_data = train_data.drop_duplicates().reset_index(drop=True)
+
+    return train_data
+
+
+def run():
+    args = parser.parse_args(sys.argv[1:])
+
+    dfs = []
+    for filename in args.data_iedb:
+        df = load_data_iedb(filename, include_mass_spec=args.include_iedb_mass_spec)
+        dfs.append(df)
+    for filename in args.data_kim2014:
+        df = load_data_kim2014(filename)
+        df["allele_peptide"] = df.allele + "_" + df.peptide
+
+        # Give precedence to IEDB data.
+        if dfs:
+            iedb_df = dfs[0]
+            iedb_df["allele_peptide"] = iedb_df.allele + "_" + iedb_df.peptide
+            print("Dropping kim2014 data present in IEDB.")
+            df = df.ix[
+                ~df.allele_peptide.isin(iedb_df.allele_peptide)
+            ]
+            print("Kim2014 data now: %s" % str(df.shape))
+        dfs.append(df)
+    for filename in args.data_systemhc_atlas:
+        df = load_data_systemhc_atlas(filename)
+        dfs.append(df)
+    for filename in args.data_abelin_mass_spec:
+        df = load_data_abelin_mass_spec(filename)
+        dfs.append(df)
+
+    df = pandas.concat(dfs, ignore_index=True)
+    print("Combined df: %s" % (str(df.shape)))
+
+    print("Removing combined duplicates")
+    df = df.drop_duplicates(["allele", "peptide", "measurement_value"])
+    print("New combined df: %s" % (str(df.shape)))
+
+    df = df[[
+        "allele",
+        "peptide",
+        "measurement_value",
+        "measurement_inequality",
+        "measurement_type",
+        "measurement_source",
+        "original_allele",
+    ]].sort_values(["allele", "peptide"]).dropna()
+
+    print("Final combined df: %s" % (str(df.shape)))
+
+    df.to_csv(args.out_csv, index=False)
+    print("Wrote: %s" % args.out_csv)
+
+if __name__ == '__main__':
+    run()

downloads-generation/models_class1_kim_benchmark/generate_hyperparameters.py

+"""
+Generate grid of hyperparameters
+"""
+
+from sys import stdout
+from copy import deepcopy
+from yaml import dump
+
+base_hyperparameters = {
+    ##########################################
+    # ENSEMBLE SIZE
+    ##########################################
+    "n_models": 4,
+
+    ##########################################
+    # OPTIMIZATION
+    ##########################################
+    "max_epochs": 500,
+    "patience": 20,
+    "early_stopping": True,
+    "validation_split": 0.1,
+    "minibatch_size": None,
+    "loss": "custom:mse_with_inequalities",
+
+    ##########################################
+    # RANDOM NEGATIVE PEPTIDES
+    ##########################################
+    "random_negative_rate": 0.0,
+    "random_negative_constant": 25,
+    "random_negative_affinity_min": 20000.0,
+    "random_negative_affinity_max": 50000.0,
+
+    ##########################################
+    # PEPTIDE REPRESENTATION
+    ##########################################
+    # One of "one-hot", "embedding", or "BLOSUM62".
+    "peptide_amino_acid_encoding": "BLOSUM62",
+    "use_embedding": False,  # maintained for backward compatability
+    "embedding_output_dim": 8,  # only used if using embedding
+    "kmer_size": 15,
+
+    ##########################################
+    # NEURAL NETWORK ARCHITECTURE
+    ##########################################
+    "locally_connected_layers": [
+        {
+            "filters": 8,
+            "activation": "tanh",
+            "kernel_size": 3
+        }
+    ],
+    "activation": "tanh",
+    "output_activation": "sigmoid",
+    "layer_sizes": [16],
+    "dense_layer_l1_regularization": None,
+    "batch_normalization": False,
+    "dropout_probability": 0.0,
+
+    ##########################################
+    # TRAINING Data
+    ##########################################
+    "train_data": {"subset": "all", "pretrain_min_points": 1000},
+}
+
+grid = []
+for train_subset in ["all", "quantitative"]:
+    for minibatch_size in [128]:
+        for dense_layer_size in [8, 16, 32, 64]:
+            for l1 in [0.0, 0.001]:
+                for num_lc in [0, 1, 2]:
+                    for lc_kernel_size in [3, 5]:
+                        new = deepcopy(base_hyperparameters)
+                        new["minibatch_size"] = minibatch_size
+                        new["train_data"]["subset"] = train_subset
+                        new["layer_sizes"] = [dense_layer_size]
+                        new["dense_layer_l1_regularization"] = l1
+                        (lc_layer,) = new["locally_connected_layers"]
+                        lc_layer['kernel_size'] = lc_kernel_size
+                        if num_lc == 0:
+                            new["locally_connected_layers"] = []
+                        elif num_lc == 1:
+                            new["locally_connected_layers"] = [lc_layer]
+                        elif num_lc == 2:
+                            new["locally_connected_layers"] = [lc_layer, deepcopy(lc_layer)]
+                        if not grid or new not in grid:
+                            grid.append(new)
+
+dump(grid, stdout)

downloads-generation/models_class1_kim_benchmark/write_validation_data.py

+"""
+Write and summarize model validation data, which is obtained by taking a full
+dataset and removing the data used for training.
+
+"""
+import argparse
+import sys
+from os.path import abspath
+
+import pandas
+import numpy
+from sklearn.model_selection import StratifiedKFold
+
+parser = argparse.ArgumentParser(usage = __doc__)
+
+parser.add_argument(
+    "--include",
+    metavar="INPUT.csv",
+    nargs="+",
+    help="Input CSV to include")
+parser.add_argument(
+    "--exclude",
+    metavar="INPUT.csv",
+    nargs="+",
+    help="Input CSV to exclude")
+parser.add_argument(
+    "--out-data",
+    metavar="RESULT.csv",
+    help="Output dadta CSV")
+parser.add_argument(
+    "--out-summary",
+    metavar="RESULT.csv",
+    help="Output summary CSV")
+parser.add_argument(
+    "--mass-spec-regex",
+    metavar="REGEX",
+    default="mass[- ]spec",
+    help="Regular expression for mass-spec data. Runs on measurement_source col."
+    "Default: %(default)s.")
+parser.add_argument(
+    "--only-alleles-present-in-exclude",
+    action="store_true",
+    default=False,
+    help="Filter to only alleles that are present in files given by --exclude. "
+    "Useful for filtering to only alleles supported by a predictor, where the "
+    "training data for the predictor is given by --exclude.")
+
+
+def run(argv):
+    args = parser.parse_args(argv)
+
+    dfs = []
+    for input in args.include:
+        df = pandas.read_csv(input)
+        dfs.append(df)
+    df = pandas.concat(dfs, ignore_index=True)
+    print("Loaded data with shape: %s" % str(df.shape))
+    del dfs
+
+    df = df.ix[
+        (df.peptide.str.len() >= 8) & (df.peptide.str.len() <= 15)
+    ]
+    print("Subselected to 8-15mers: %s" % (str(df.shape)))
+
+    if args.exclude:
+        exclude_dfs = []
+        for exclude in args.exclude:
+            exclude_df = pandas.read_csv(exclude)
+            exclude_dfs.append(exclude_df)
+        exclude_df = pandas.concat(exclude_dfs, ignore_index=True)
+        del exclude_dfs
+
+        df["_key"] = df.allele + "__" + df.peptide
+        exclude_df["_key"] = exclude_df.allele + "__" + exclude_df.peptide
+        df["_excluded"] = df._key.isin(exclude_df._key.unique())
+        print("Excluding measurements per allele (counts): ")
+        print(df.groupby("allele")._excluded.sum())
+
+        print("Excluding measurements per allele (fractions): ")
+        print(df.groupby("allele")._excluded.mean())
+
+        df = df.loc[~df._excluded]
+        del df["_excluded"]
+        del df["_key"]
+
+        if args.only_alleles_present_in_exclude:
+            df = df.loc[df.allele.isin(exclude_df.allele.unique())]
+
+    df["mass_spec"] = df.measurement_source.str.contains(args.mass_spec_regex)
+    df.loc[df.mass_spec , "measurement_inequality"] = "mass_spec"
+
+    if args.out_summary:
+        summary_df = df.groupby(
+            ["allele", "measurement_inequality"]
+        )["measurement_value"].count().unstack().fillna(0).astype(int)
+        summary_df["total"] = summary_df.sum(1)
+        summary_df.to_csv(args.out_summary)
+        print("Wrote: %s" % args.out_summary)
+
+    if args.out_data:
+        df.to_csv(args.out_data, index=False)
+        print("Wrote: %s" % args.out_data)
+
+if __name__ == '__main__':
+    run(sys.argv[1:])

mhcflurry/train_allele_specific_models_command.py

@@ -144,7 +144,7 @@ def run(argv=sys.argv[1:]):
     configure_logging(verbose=args.verbosity > 1)
 
     hyperparameters_lst = yaml.load(open(args.hyperparameters))
-    assert isinstance(hyperparameters_lst, list)
+    assert isinstance(hyperparameters_lst, list), hyperparameters_lst
     print("Loaded hyperparameters list: %s" % str(hyperparameters_lst))
 
     df = pandas.read_csv(args.data)
@@ -171,8 +171,8 @@ def run(argv=sys.argv[1:]):
         ].index)
 
     # Allele names in data are assumed to be already normalized.
+    print("Selected %d/%d alleles: %s" % (len(alleles), df.allele.nunique(), ' '.join(alleles)))
     df = df.loc[df.allele.isin(alleles)].dropna()
-    print("Selected %d alleles: %s" % (len(alleles), ' '.join(alleles)))
 
     if args.held_out_fraction_reciprocal:
         df = subselect_df_held_out(
@@ -227,6 +227,7 @@ def run(argv=sys.argv[1:]):
             allele_sequences = allele_sequences.loc[
                 allele_sequences.index.isin(df.allele.unique())
             ]
+            print("Allele sequences matching train data: %d" % len(allele_sequences))
             blosum_encoding = (
                 AlleleEncoding(
                     allele_sequences.index.values,
@@ -377,7 +378,6 @@ def train_model(
         alleles = []
         while not alleles or data_size_by_allele.loc[alleles].sum() < pretrain_min_points:
             alleles.append(similar_alleles.pop(0))
-        print(alleles)
         data = data.loc[data.allele.isin(alleles)]
         assert len(data) >= pretrain_min_points, (len(data), pretrain_min_points)
         train_rounds = (data.allele == allele).astype(int).values