scripts/temstapro

#!/usr/bin/env python3

# Program that makes thermostability predictions

from optparse import OptionParser
from datetime import datetime
import sys
import os
import numpy
from torch.utils.data import DataLoader
from torch.utils.data import TensorDataset
import torch

PARAMETERS = {
	"PT_MODEL_PATH": "Rostlab/prot_t5_xl_half_uniref50-enc",
	"DATASET": "major",
	"EMB_TYPE": "mean",
	"CLASSIFIER_TYPE": "imbal",
	"THRESHOLDS": {
		":(40-65]:": ["40", "45", "50", "55", "60", "65"],
		":(40-80]:": ["40", "45", "50", "55", "60", "65", "70", "75", "80"],
	},
	"SEEDS": ["1", "2", "3", "4", "5"],
	"INPUT_SIZE": 1024,
	"HIDDEN_LAYER_SIZES": [256, 128],
	"DEVICE": torch.device("cuda:0" if torch.cuda.is_available() else "cpu"),
	"THRESHOLDS_RANGE": ":(40-65]:",
	"TEMPERATURE_RANGES": {
		":(40-65]:": ["<40", "[40-45)", "[45-50)", "[50-55)", "[55-60)", 
			"[60-65)", "65<="],
		":(40-80]:": ["<40", "[40-45)", "[45-50)", "[50-55)", "[55-60)", 
			"[60-65)", "[65-70)", "[70-75)", "[75-80)", "80<="],
	},
	"THERMOPHILICITY_LABELS": {
		"mesophilic": ["<40", "[40-45)", "<45"],
		"thermophilic": ["[45-50)", "[50-55)", "[55-60)", "[60-65)", 
			"65<=", "[65-70)", "[70-75)", "<75"],
		"hyperthermophilic": ["[75-80)", "80<="]
	},
	"PRINT_THERMOPHILICITY": {
		":(40-65]:": False,
		":(40-80]:": True
	}
}

SCRIPT_DIR = os.path.dirname(os.path.abspath(__file__))
PROJECT_DIR = os.path.dirname(SCRIPT_DIR)

parser = OptionParser()

parser.add_option("--input-fasta", "-f", dest="fasta",
	default=None, help="path to the input FASTA file.")

parser.add_option("--embeddings-dir", "-e", dest="emb_dir",
	default=None, help="path to the directory to which embeddings "+\
	"files will be saved (cache).")

parser.add_option("--PT-directory", "-d", dest="pt_dir",
	default=None, help="path to the directory of ProtTrans model.")

parser.add_option("--temstapro-directory", "-t", dest="tsp_dir",
	default=PROJECT_DIR, help="path to the directory of TemStaPro program "+\
	"with its dependencies.")

parser.add_option("--more-thresholds", dest="more_thresholds",
	action="store_true", help="option for the mode that outputs "+\
	"additional predictions for upper temperature thresholds and the "+\
	"thremophilicity label")

parser.add_option("--mean-output", dest="mean_out",
	default=None, help="path to the output TSV file with mean predictions. "+\
	"Predictions made from the mean embeddings are always printed to STDOUT."+\
	" If this option is given, the output is directed to the given file")

parser.add_option("--per-res-output", dest="per_res_out",
	default=None, help="path to the output TSV file with per-residue "+\
	"predictions.")

parser.add_option("--per-segment-output", dest="per_segment_out",
	default=None, help="path to the output TSV file with per-residue "+\
	"predictions made for each segment of the sequence.")

parser.add_option("--segment-size", dest="segment_size",
	default=41, help="option to set the window size for average smoothening "+\
	"of per residue embeddings ('per-segment-output' option). Default: 41.")

parser.add_option("--window-size-predictions", "-w", 
	dest="window_size_predictions",
	default=81, help="option to set the window size for average smoothening "+\
	"of per residue predictions for plotting (option for 'per-res-output' "+\
	"and 'per-segment-output'). Default: 81.")

parser.add_option("--per-residue-plot-dir", "-p", dest="plot_dir",
	default=None, help="path to the directory to which inferences "+\
	"plots will be saved (option for 'per-res-output' and "+\
	"'per-res-segment-output' modes. Default: './'.")

parser.add_option("--curve-smoothening", "-c", dest="curve_smoothening",
	default=False, action="store_true", 
	help="option for 'per-segment-output' run mode, which adjusts the "+\
	"plot by making an additional smoothening of the curve.")

parser.add_option("--portion-size", dest="portion_size",
	default=1000, 
	help="option to set the portions', into which to divide the input "+\
	"of sequences, maximum size. If no division is needed, set the "+\
	"option to 0. Default: 1000.")

parser.add_option("--version", "-v", dest="version",
	default=False, action="store_true",
	help="print version of the program and exit.")

(options, args) = parser.parse_args()

if(options.version):
	print(f"TemStaPro 0.2.{int(os.popen('git rev-list --count HEAD').read().strip())-61}")
	exit()

options.window_size_predictions = int(options.window_size_predictions)
options.segment_size = int(options.segment_size)
if(options.more_thresholds): PARAMETERS['THRESHOLDS_RANGE'] = ":(40-80]:"

try:
	assert (options.fasta != None), f"{sys.argv[0]}: a FASTA file is required."
except AssertionError as message:
	print(message, file=sys.stderr)
	exit()

try:
	assert (options.pt_dir != None), (
		f"{sys.argv[0]}: a path to the ProtTrans model location is required."
	)
except AssertionError as message:
	print(message, file=sys.stderr)
	exit()

temstapro_dir = os.path.abspath(options.tsp_dir)
PARAMETERS["CLASSIFIERS_DIR"] = os.path.join(temstapro_dir, "weight")

# Importing local modules

sys.path.append(os.path.join(temstapro_dir, "scripts"))
sys.path.append(os.path.join(temstapro_dir, "model"))

import prottrans_models
import data_process
import model_flow
import results

# Standardization of the FASTA file
(sequences, orig_headers, orig_seqs) = prottrans_models.process_FASTA(options.fasta)

# Loading the ProtTrans model
print("%s: beginning to load the model " % datetime.now(), file=sys.stderr)

pt_model, tokenizer = prottrans_models.load_model_and_tokenizer(options.pt_dir, 
	PARAMETERS["PT_MODEL_PATH"])

print("%s: finished loading the model" % datetime.now(), file=sys.stderr)

# Dividing sequences into portions
options.portion_size = int(options.portion_size)
if(options.portion_size == 0): options.portion_size = len(sequences)

per_res_mode = (options.per_res_out or options.per_segment_out)

for i in range(0, len(list(sequences.keys())), options.portion_size):
	portion_keys = list(sequences.keys())[i:i+options.portion_size]
	
	sequences_portion = {}
	for key in portion_keys:
		sequences_portion[key] = sequences[key]

	# Check which sequences do not have embeddings generated
	if(options.emb_dir and os.path.exists(options.emb_dir)):
		seqs_wo_emb_portion = data_process.get_sequences_without_embeddings(
			sequences_portion, options.emb_dir, per_res=per_res_mode)
	else:
		seqs_wo_emb_portion = sequences_portion

	embeddings = {}
	per_res_dataset = {}
	per_res_sequences_portion = {}
 
	if(len(seqs_wo_emb_portion)):
		gen_emb_start = datetime.now()
		print(f"{datetime.now()}: beginning to generate embeddings", file=sys.stderr)

		# Generating embeddings
		embeddings = prottrans_models.get_embeddings(pt_model, tokenizer, 
			seqs_wo_emb_portion, 
			per_residue=per_res_mode, 
			per_protein=True)

		gen_emb_end = datetime.now()
		
		# If cache given, save embeddings
		if(options.emb_dir and os.path.exists(options.emb_dir)):
			if(per_res_mode):
				prottrans_models.save_embeddings(seqs_wo_emb_portion, embeddings,
					options.emb_dir, "per_res")
			prottrans_models.save_embeddings(seqs_wo_emb_portion, embeddings, 
				options.emb_dir, "mean")
		elif(options.emb_dir and not os.path.exists(options.emb_dir)):
			print("The given directory (option -e) does not exist, "+\
				"embeddings' PT files will not be saved.", file=sys.stderr)

		try:
			prottrans_models.print_embeddings_generation_stats(i, 
				options.portion_size, embeddings, seqs_wo_emb_portion, 
				gen_emb_start, gen_emb_end)
		except ZeroDivisionError:
			print(f"{sys.argv[0]}: no embeddings were generated.", file=sys.stderr)
			sys.exit(1)

	# Collecting the required type of embeddings
	dataset = data_process.collect_mean_embeddings(sequences_portion, 
		embeddings=embeddings, emb_dir=options.emb_dir, 
		input_size=PARAMETERS["INPUT_SIZE"])

	if(options.per_res_out):
		per_res_dataset = data_process.collect_per_res_embeddings(sequences_portion, 
			orig_seqs, embeddings=embeddings, emb_dir=options.emb_dir, 
			input_size=PARAMETERS["INPUT_SIZE"])
		per_res_sequences_portion = per_res_dataset["z_test"]
	elif(options.per_segment_out):
		per_res_dataset = data_process.collect_per_res_embeddings(sequences_portion, 
			orig_seqs, embeddings=embeddings,
			emb_dir=options.emb_dir, input_size=PARAMETERS["INPUT_SIZE"], smoothen=True, 
			window_size=options.segment_size)
		per_res_sequences_portion = per_res_dataset["z_test"]

	test_loader, per_res_test_loader = model_flow.prepare_data_loaders([
		dataset, per_res_dataset], 'test')

	print("%s: beginning to make inferences" % datetime.now(), 
		file=sys.stderr)

	averaged_inferences, binary_inferences, labels, clashes = model_flow.make_inferences(
		sequences_portion, per_res_sequences_portion, test_loader, 
		per_res_test_loader, PARAMETERS, PARAMETERS["THRESHOLDS_RANGE"])

	print("%s: finished making inferences" % datetime.now(), file=sys.stderr)
			
	# Processing results
	for j, loader in enumerate([test_loader, per_res_test_loader]):
		if(loader is None): break
		for seq in averaged_inferences[j].keys():
			labels[j][seq].append(results.get_temperature_label(
				averaged_inferences[j][seq], 
				PARAMETERS["TEMPERATURE_RANGES"][PARAMETERS["THRESHOLDS_RANGE"]], left_hand=True))
			labels[j][seq].append(results.get_temperature_label(
				averaged_inferences[j][seq],
				PARAMETERS["TEMPERATURE_RANGES"][PARAMETERS["THRESHOLDS_RANGE"]], left_hand=False))
			clashes[j][seq].append(results.detect_clash(averaged_inferences[j][seq],
				left_hand=True))

	# Processing printing of mean predictions
	if(options.mean_out):
		os.system(f"mkdir -p {os.path.dirname(options.mean_out)}")
		f_mean = open(options.mean_out, "w") if i == 0 else open(options.mean_out, "a")
	else:
		f_mean = sys.stdout

	if(i == 0): results.print_inferences_header(f_mean, 
		PARAMETERS["THRESHOLDS"][PARAMETERS["THRESHOLDS_RANGE"]], 
		PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])

	results.print_inferences(averaged_inferences[0], binary_inferences[0],
		orig_headers, labels[0], clashes[0], 
		PARAMETERS["THERMOPHILICITY_LABELS"], f_mean, orig_seqs,
		"mean", PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])

	# Printing per-residue inferences
	if(options.per_res_out):
		os.system(f"mkdir -p {os.path.dirname(options.per_res_out)}")
		f_per_res = open(options.per_res_out, "w") if i == 0 else open(options.per_res_out, "a")
		if(i == 0): results.print_inferences_header(f_per_res, 
			PARAMETERS["THRESHOLDS"][PARAMETERS["THRESHOLDS_RANGE"]], 
			PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])

		results.print_inferences(averaged_inferences[1], binary_inferences[1], 
			orig_headers, labels[1],
			clashes[1], PARAMETERS["THERMOPHILICITY_LABELS"],
			f_per_res, per_res_sequences_portion, "per-res", 
			PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])
	elif(options.per_segment_out):
		os.system(f"mkdir -p {os.path.dirname(options.per_segment_out)}")
		f_per_res = open(options.per_segment_out, "w") if i == 0 else open(options.per_segment_out, "a")
		if(i == 0): results.print_inferences_header(f_per_res, 
			PARAMETERS["THRESHOLDS"][PARAMETERS["THRESHOLDS_RANGE"]],
			PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])

		results.print_inferences(averaged_inferences[1], binary_inferences[1], 
			orig_headers, labels[1],
			clashes[1], PARAMETERS["THERMOPHILICITY_LABELS"], f_per_res, 
			per_res_sequences_portion, "per-segment",
			PARAMETERS["PRINT_THERMOPHILICITY"][PARAMETERS["THRESHOLDS_RANGE"]])

	# Plotting inferences
	if(options.plot_dir):
		os.system(f"mkdir -p {options.plot_dir}")
		results.plot_inferences(
			options.per_res_out, options.per_segment_out,
			averaged_inferences[1],
			PARAMETERS["THRESHOLDS"][PARAMETERS["THRESHOLDS_RANGE"]], options.plot_dir,
			options.window_size_predictions, options.segment_size, 
			options.curve_smoothening)