File size: 17,928 Bytes
80b6a2c
 
 
 
 
 
 
 
 
29899b4
 
 
 
80b6a2c
 
29899b4
 
9da03b7
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
80b6a2c
 
 
29899b4
 
80b6a2c
 
 
 
29899b4
 
 
80b6a2c
29899b4
 
 
 
 
 
 
 
 
 
 
80b6a2c
 
 
 
 
 
 
29899b4
 
80b6a2c
 
9da03b7
 
 
 
 
4c4b1fc
 
9da03b7
 
 
 
 
 
4c4b1fc
 
9da03b7
80b6a2c
 
 
29899b4
 
 
 
 
 
80b6a2c
29899b4
 
 
80b6a2c
 
 
 
29899b4
 
 
 
 
80b6a2c
29899b4
80b6a2c
29899b4
 
 
 
 
 
80b6a2c
 
 
29899b4
 
 
80b6a2c
 
29899b4
80b6a2c
 
 
 
 
 
 
 
29899b4
 
 
 
80b6a2c
29899b4
9da03b7
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
29899b4
9da03b7
29899b4
 
 
80b6a2c
29899b4
 
 
 
80b6a2c
29899b4
 
 
 
 
80b6a2c
29899b4
 
 
 
80b6a2c
 
29899b4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
80b6a2c
 
29899b4
80b6a2c
 
29899b4
 
 
 
 
80b6a2c
29899b4
80b6a2c
 
 
29899b4
 
80b6a2c
29899b4
 
9da03b7
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4c4b1fc
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9da03b7
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
29899b4
80b6a2c
 
29899b4
9da03b7
bc0d37c
 
 
9da03b7
bc0d37c
29899b4
9da03b7
29899b4
 
 
 
 
 
 
9da03b7
29899b4
9da03b7
29899b4
 
 
9da03b7
29899b4
 
 
 
 
9da03b7
29899b4
 
 
 
9da03b7
 
29899b4
 
 
 
 
 
 
 
 
 
 
 
 
80b6a2c
29899b4
80b6a2c
4c4b1fc
 
9da03b7
 
 
 
4c4b1fc
 
 
29899b4
 
 
9da03b7
29899b4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
from collections import Counter, defaultdict
from ortools.linear_solver import pywraplp
import random
from omegaconf import DictConfig
import pandas as pd
from pathlib import Path
import os
import numpy as np
from sklearn.model_selection import train_test_split
from dpacman.data_tasks.fimo.post_fimo import get_reverse_complement
import json
import rootutils
from dpacman.utils import pylogger

root = rootutils.setup_root(__file__, indicator=".project-root", pythonpath=True)
logger = pylogger.RankedLogger(__name__, rank_zero_only=True)

def split_with_predefined_test(
    full_df = pd.DataFrame(),
    split_names=("train", "val", "test"),
    test_trs=None,
    test_dnas=None,
    ratios=(0.8, 0.1, 0.1),
):
    """
    Method for splitting into train and val with a predefined test set. 
    The proteins in the test set, and the DNA clusters of the DNAs they're associated with, must be excluded from train and val. 
    The remaining rows for train and val are split to preserve 80/10/10 as best as possible. 
    """
    test = full_df.copy(deep=True)
    if test_trs is not None:
        test = test.loc[test["tr_seqid"].isin(test_trs)].reset_index(drop=True)
    if test_dnas is not None:
        test = test.loc[test["dna_seqid"].isin(test_dnas)].reset_index(drop=True)
    
    tr_clusters_to_exclude = test["tr_cluster_rep"].unique().tolist()
    dna_clusters_to_exclude = test["dna_cluster_rep"].unique().tolist()
    
    remaining = full_df.loc[
        (~full_df["tr_cluster_rep"].isin(tr_clusters_to_exclude)) & 
        (~full_df["dna_cluster_rep"].isin(dna_clusters_to_exclude))  
    ].reset_index(drop=True)
    
    test_ids = test["ID"].unique().tolist()
    remaining_ids = remaining["ID"].unique().tolist()
    remaining_clusters = remaining["dna_cluster_rep"].unique().tolist()
    lost_rows = full_df.loc[
        (~full_df["ID"].isin(test_ids)) & 
        (~full_df["ID"].isin(remaining_ids))
    ]
    
    logger.info(f"Rows in test: {len(test)}")
    logger.info(f"Rows to be split between train and val: {len(remaining)}")
    total_rows = len(test) + len(remaining)
    logger.info(f"Total rows: {total_rows}. Test percentage: {100*len(test)/total_rows:.2f}%")
    logger.info(f"Lost rows: {len(lost_rows)}")
    
    train_ratio_from_remaining = round((0.8*total_rows)/len(remaining), 2)
    # use sklearn
    test_size_1 = 1 - train_ratio_from_remaining
    logger.info(
        f"\tPerforming first split: non-test clusters -> train clusters ({round(1-test_size_1,3)}) and val ({test_size_1})"
    )
    X = remaining_clusters
    y = [0] * len(remaining_clusters)
    X_train, X_val, y_train, y_val = train_test_split(
        X, y, test_size=test_size_1, random_state=0
    )

    train = remaining.loc[remaining["dna_cluster_rep"].isin(X_train)]
    val = remaining.loc[remaining["dna_cluster_rep"].isin(X_val)]
    leaky_test = lost_rows
    
    kept_by_split = {
        "train": len(X_train),
        "val": len(X_val),
        "test": len(test["dna_cluster_rep"].unique())
    }
    splits = {
        "train": train,
        "val": val,
        "test": test,
        "leaky_test": leaky_test
    }
    return splits, kept_by_split

def split_bipartite_fast(
    dna_clusters,
    split_names=("train", "val", "test"),
    ratios=(0.8, 0.1, 0.1),
):
    # use sklearn
    test_size_1 = 0.2
    test_size_2 = 0.5
    logger.info(
        f"\tPerforming first split: all clusters -> train clusters ({round(1-test_size_1,3)}) and other ({test_size_1})"
    )
    X = dna_clusters
    y = [0] * len(dna_clusters)
    X_train, X_test, y_train, y_test = train_test_split(
        X, y, test_size=test_size_1, random_state=0
    )
    logger.info(
        f"\tPerforming second split: other -> val clusters ({round(1-test_size_2,3)}) and test clusters ({test_size_2})"
    )
    X_val, X_test, y_val, y_test = train_test_split(
        X_test, y_test, test_size=test_size_2, random_state=0
    )

    dna_assign = {}
    for x in X_train:
        dna_assign[x] = "train"
    for x in X_val:
        dna_assign[x] = "val"
    for x in X_test:
        dna_assign[x] = "test"

    kept_by_split = {"train": len(X_train), "val": len(X_val), "test": len(X_test)}
    return dna_assign, kept_by_split

# construct new labels 
def convert_scores(scores, mode=1):
    """
    Two modes: 1 means FIMO peaks get 1. 0 means FIMO peaks get their max score
    """
    svec = [int(x) for x in scores.split(",")]
    max_score = max(svec)
    if mode ==1:
        binary_svec = [0 if x<max_score else 1 for x in svec]
        assert(svec.count(max_score)==binary_svec.count(1))
    else:
        binary_svec = [0 if x<max_score else max_score for x in svec]
        assert(svec.count(max_score)==binary_svec.count(max_score))
    binary_svec = ",".join([str(x) for x in binary_svec])
    return binary_svec
    
def print_split_ratios(kept_by_split):
    total = sum(kept_by_split.values())
    train_pcnt = 100 * kept_by_split["train"] / total
    val_pcnt = 100 * kept_by_split["val"] / total
    test_pcnt = 100 * kept_by_split["test"] / total
    logger.info(
        f"Cluster distribution - Train: {train_pcnt:.2f}%, Val: {val_pcnt:.2f}%, Test: {test_pcnt:.2f}%"
    )


def make_edges(
    processed_fimo_path: str, protein_cluster_path: str, dna_cluster_path: str
):
    """
    Make edges for input to the splitting algorithm. Edges consist of: (tr_cluster_rep)_(dna_cluster_rep) where the cluster rep is the sequence ID
    """
    # Read cluser data
    protein_clusters = pd.read_csv(protein_cluster_path, header=None, sep="\t")
    protein_clusters.columns = ["tr_cluster_rep", "tr_seqid"]

    dna_clusters = pd.read_csv(dna_cluster_path, header=None, sep="\t")
    dna_clusters.columns = ["dna_cluster_rep", "dna_seqid"]

    # Read datapoints
    edges = pd.read_parquet(processed_fimo_path)
    edges = pd.merge(edges, dna_clusters, on="dna_seqid", how="left")
    edges = pd.merge(edges, protein_clusters, on="tr_seqid", how="left")
    edges["edge"] = edges.apply(
        lambda row: (row["tr_cluster_rep"], row["dna_cluster_rep"]), axis=1
    )

    logger.info(f"Total unique edges: {len(edges['edge'].unique().tolist())}")
    dup_edges = edges.loc[edges.duplicated("edge")]["edge"].unique().tolist()
    logger.info(f"Total edges with >1 datapoint: {len(dup_edges)}")
    logger.info(
        f"Total datapoints belonging to a duplicate edge: {len(edges.loc[edges['edge'].isin(dup_edges)])}"
    )
    return edges


def check_validity(train, val, test, split_by="both"):
    """
    Rigorous check for no overlap
    Columns = ["ID","dna_sequence","tr_sequence","tr_cluster_rep","dna_cluster_rep", "scores","split"]
    """
    train_ids = set(train["ID"].unique().tolist())
    val_ids = set(val["ID"].unique().tolist())
    test_ids = set(test["ID"].unique().tolist())

    assert len(train_ids.intersection(val_ids)) == 0
    assert len(train_ids.intersection(test_ids)) == 0
    assert len(val_ids.intersection(test_ids)) == 0
    logger.info(f"Pass! No overlap in IDs")

    # Investigate TR intersection. No assertions unless we are explicitly splitting on this. 
    train_tr_seqs = set(train["tr_sequence"].unique().tolist())
    val_tr_seqs = set(val["tr_sequence"].unique().tolist())
    test_tr_seqs = set(test["tr_sequence"].unique().tolist())
    
    train_tr_reps = set(train["tr_cluster_rep"].unique().tolist())
    val_tr_reps = set(val["tr_cluster_rep"].unique().tolist())
    test_tr_reps = set(test["tr_cluster_rep"].unique().tolist())
    
    logger.info(f"Train-Val TR intersection: {len(train_tr_seqs.intersection(val_tr_seqs))}")
    logger.info(f"Train-Test TR intersection: {len(train_tr_seqs.intersection(test_tr_seqs))}")
    logger.info(f"Val-Test TR intersection: {len(val_tr_seqs.intersection(test_tr_seqs))}")
    
    logger.info(f"Train-Val TR Cluster Rep intersection: {len(train_tr_reps.intersection(val_tr_reps))}")
    logger.info(f"Train-Test TR Cluster Rep intersection: {len(train_tr_reps.intersection(test_tr_reps))}")
    logger.info(f"Val-Test TR Cluster Rep intersection: {len(val_tr_reps.intersection(test_tr_reps))}")
    
    # Investigate DNA intersection. No assertions unless we are explicitly splitting on this. 
    train_dna_seqs = set(train["dna_sequence"].unique().tolist())
    val_dna_seqs = set(val["dna_sequence"].unique().tolist())
    test_dna_seqs = set(test["dna_sequence"].unique().tolist())
    
    train_dna_reps = set(train["dna_cluster_rep"].unique().tolist())
    val_dna_reps = set(val["dna_cluster_rep"].unique().tolist())
    test_dna_reps = set(test["dna_cluster_rep"].unique().tolist())
    
    logger.info(f"Train-Val DNA intersection: {len(train_dna_seqs.intersection(val_dna_seqs))}")
    logger.info(f"Train-Test DNA intersection: {len(train_dna_seqs.intersection(test_dna_seqs))}")
    logger.info(f"Val-Test DNA intersection: {len(val_dna_seqs.intersection(test_dna_seqs))}")
    
    logger.info(f"Train-Val DNA Cluster Rep intersection: {len(train_dna_reps.intersection(val_dna_reps))}")
    logger.info(f"Train-Test DNA Cluster Rep intersection: {len(train_dna_reps.intersection(test_dna_reps))}")
    logger.info(f"Val-Test DNA Cluster Rep intersection: {len(val_dna_reps.intersection(test_dna_reps))}")

    if split_by != "dna":
        assert len(train_tr_seqs.intersection(val_tr_seqs)) == 0
        assert len(train_tr_seqs.intersection(test_tr_seqs)) == 0
        assert len(val_tr_seqs.intersection(test_tr_seqs)) == 0
        logger.info(f"Pass! No overlap in TR sequences")

        assert len(train_tr_reps.intersection(val_tr_reps)) == 0
        assert len(train_tr_reps.intersection(test_tr_reps)) == 0
        assert len(val_tr_reps.intersection(test_tr_reps)) == 0
        logger.info(f"Pass! No overlap in TR cluster reps")

    if split_by != "protein":
        assert len(train_dna_seqs.intersection(val_dna_seqs)) == 0
        assert len(train_dna_seqs.intersection(test_dna_seqs)) == 0
        assert len(val_dna_seqs.intersection(test_dna_seqs)) == 0
        logger.info(f"Pass! No overlap in DNA sequences")

        assert len(train_dna_reps.intersection(val_dna_reps)) == 0
        assert len(train_dna_reps.intersection(test_dna_reps)) == 0
        assert len(val_dna_reps.intersection(test_dna_reps)) == 0
        logger.info(f"Pass! No overlap in DNA cluster reps")


def augment_rc(df):
    """
    Get the reverse complement and add it as a datapoint, effectively doubling the dataset.
    Also flip the orientation of the scores

    columns = ["ID","dna_sequence","tr_sequence","tr_cluster_rep","dna_cluster_rep", "scores","split"]
    """
    df_rc = df.copy(deep=True)

    df_rc["dna_sequence"] = df_rc["dna_sequence"].apply(
        lambda x: get_reverse_complement(x)
    )
    df_rc["ID"] = df_rc["ID"] + "_rc"
    df_rc["scores"] = df_rc["scores"].apply(lambda s: ",".join(s.split(",")[::-1]))

    final_df = pd.concat([df, df_rc]).reset_index(drop=True)

    return final_df


def main(cfg: DictConfig):
    """
    Take a set of DNA clusters + protein clusters, and create the best possible splits into train/val/test.
    """
    # construct edges from training data
    edge_df = make_edges(
        processed_fimo_path=Path(root) / cfg.data_task.input_data_path,
        protein_cluster_path=Path(root) / cfg.data_task.cluster_output_paths.protein,
        dna_cluster_path=Path(root) / cfg.data_task.cluster_output_paths.dna,
    )
    edges = edge_df["edge"].unique().tolist()

    # figure out if we actually even have a conflict
    total_proteins = len(edge_df["tr_seqid"].unique().tolist())
    total_protein_clusters = len(edge_df["tr_cluster_rep"].unique().tolist())

    no_protein_overlap = (total_proteins) == (total_protein_clusters)
    logger.info(f"All proteins are in their own clusters: {no_protein_overlap}")

    if cfg.data_task.split_by == "dna":
        if cfg.data_task.test_trs or cfg.data_task.test_dnas:
            logger.info(f"Splitting with predefined trs/dnas reserved for test set")
            splits, kept_by_split = split_with_predefined_test(
                full_df=edge_df,
                split_names=("train", "val", "test"),
                test_trs=cfg.data_task.test_trs if cfg.data_task.test_trs else None,
                test_dnas=cfg.data_task.test_dnas if cfg.data_task.test_dnas else None,
                ratios=(0.8, 0.1, 0.1),
            )
            train = splits["train"]
            train["split"]=["train"]*len(train)
            val = splits["val"]
            val["split"]=["val"]*len(val)
            test = splits["test"]
            test["split"]=["test"]*len(test)
            leaky_test = splits["leaky_test"]
            leaky_test["split"]=["leaky_test"]*len(leaky_test)
        else:
            logger.info(f"Easy split: all proteins are in their own clusters.")
            dna_clusters = edge_df["dna_cluster_rep"].unique().tolist()
            results = split_bipartite_fast(
                dna_clusters,
                split_names=("train", "val", "test"),
                ratios=(
                    cfg.data_task.train_ratio,
                    cfg.data_task.val_ratio,
                    cfg.data_task.test_ratio,
                ),
            )
            dna_assign, kept_by_split = results

            # assign datapoints to cluster by their DNA cluster rep
            edge_df["split"] = edge_df["dna_cluster_rep"].map(dna_assign)
            train = edge_df.loc[edge_df["split"] == "train"].reset_index(drop=True)
            val = edge_df.loc[edge_df["split"] == "val"].reset_index(drop=True)
            test = edge_df.loc[edge_df["split"] == "test"].reset_index(drop=True)
            leaky_test = pd.DataFrame(columns=edge_df.columns)

        # Print ratios: hopefully close to desired (e.g. 80/10/10)
        print_split_ratios(kept_by_split)

        # Make train, val, test sets
        # make sure no ID is duplicate
        assert len(edge_df["ID"].unique()) == len(edge_df)
        split_cols = [
            "ID",
            "dna_sequence",
            "tr_sequence",
            "tr_cluster_rep",
            "dna_cluster_rep",
            "scores",
            "split",
        ]
        train = train[split_cols]
        val = val[split_cols]
        test = test[split_cols]
        leaky_test = leaky_test[split_cols]

    # ensure there is no overlap
    check_validity(train, val, test, split_by=cfg.data_task.split_by)

    total = sum([len(train), len(val), len(test), len(leaky_test)])
    logger.info(f"Length of train dataset: {len(train)} ({100*len(train)/total:.2f}%)")
    logger.info(f"Length of val dataset: {len(val)} ({100*len(val)/total:.2f}%)")
    logger.info(f"Length of test dataset: {len(test)} ({100*len(test)/total:.2f}%)")
    logger.info(f"Length of leaky_test dataset: {len(leaky_test)} ({100*len(leaky_test)/total:.2f}%)")
    logger.info(f"Total sequences = {total}. Same as edges size? {total==len(edge_df)}")

    og_unique_dna = pd.concat([train, val, test, leaky_test])
    og_unique_dna = len(og_unique_dna["dna_sequence"].unique())

    ## Now do RC data augmentation if asked
    if cfg.data_task.augment_rc:
        train = augment_rc(train)
        val = augment_rc(val)
        test = augment_rc(test)
        leaky_test = augment_rc(leaky_test)

        logger.info(f"Added reverse complement sequences to train, val, and test (and leaky test)")

        check_validity(train, val, test, split_by=cfg.data_task.split_by)

        total = sum([len(train), len(val), len(test), len(leaky_test)])
        logger.info(
            f"Length of train dataset: {len(train)} ({100*len(train)/total:.2f}%)"
        )
        logger.info(f"Length of val dataset: {len(val)} ({100*len(val)/total:.2f}%)")
        logger.info(f"Length of test dataset: {len(test)} ({100*len(test)/total:.2f}%)")
        logger.info(f"Length of leaky_test dataset: {len(leaky_test)} ({100*len(leaky_test)/total:.2f}%)")
        logger.info(
            f"Total sequences = {total}. Same as edges size? {total==len(edge_df)}"
        )

        # since we've added all these new DNA sequences, we do need a new mapping of seq id to dna sequence
        all_data = pd.concat([train, val, test, leaky_test])
        all_data["dna_seqid"] = all_data["ID"].str.split("_", n=1, expand=True)[1]
        dna_dict = dict(zip(all_data["dna_seqid"], all_data["dna_sequence"]))
        assert len(dna_dict) == len(all_data.drop_duplicates(["dna_sequence"]))
        new_map_path = str(Path(root) / cfg.data_task.dna_map_path).replace(
            ".json", "_with_rc.json"
        )

        with open(new_map_path, "w") as f:
            json.dump(dna_dict, f, indent=2)
        logger.info(
            f"Saved DNA maps with reverse complements (len {len(dna_dict)}=2*original map of len {og_unique_dna}=={len(dna_dict)==2*og_unique_dna}) to {new_map_path}"
        )

    # create the output dir
    split_out_dir = Path(root) / cfg.data_task.split_out_dir
    os.makedirs(split_out_dir, exist_ok=True)
    
    # add binary_scores to allow other training modes
    train["fimo_binary_sores"] = train["scores"].apply(lambda x: convert_scores(x, mode=1))
    val["fimo_binary_sores"] = val["scores"].apply(lambda x: convert_scores(x, mode=1))
    test["fimo_binary_sores"] = test["scores"].apply(lambda x: convert_scores(x, mode=1))
    leaky_test["fimo_binary_sores"] = leaky_test["scores"].apply(lambda x: convert_scores(x, mode=1))
    
    # slect final cols and save
    split_final_cols = ["ID", "dna_sequence", "tr_sequence", "scores", "fimo_binary_sores", "split"]
    train[split_final_cols].to_csv(split_out_dir / "train.csv", index=False)
    val[split_final_cols].to_csv(split_out_dir / "val.csv", index=False)
    test[split_final_cols].to_csv(split_out_dir / "test.csv", index=False)
    leaky_test[split_final_cols].to_csv(split_out_dir / "leaky_test.csv", index=False)
    logger.info(f"Saved all splits to {split_out_dir}")