NegBioDB / config.yaml
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NegBioDB final: 4 domains, fully audited
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# NegBioDB Configuration
# Source of truth for thresholds, paths, and pipeline settings.
# === Inactivity Thresholds ===
inactivity_threshold_nm: 10000 # 10 uM in nM; compound inactive if IC50/Ki/Kd > this
positive_pchembl_min: 6.0 # pChEMBL >= 6 for positives (IC50 <= 1 uM)
borderline_exclusion:
lower: 4.5 # Exclude pChEMBL >= 4.5 from negative pool
upper: 6.0 # Matches positive_pchembl_min; effective gap: [4.5, 6.0)
davis_inactive_pkd_threshold: 5.0 # DAVIS: inactive if pKd <= 5 (NOT strictly < 5)
davis_active_pkd_threshold: 7.0 # DAVIS: active if pKd >= 7 (Kd <= 100 nM)
# === ChEMBL ETL Policy ===
# Core benchmark should remain conservative by default.
# Optional activity_comment route can be enabled for recall-focused expansion.
chembl_etl:
include_activity_comment: false
inactive_activity_comments:
- "Not Active"
- "Inactive"
- "Not active"
- "inactive"
# === ML Split Configuration ===
split_ratios:
train: 0.7
val: 0.1
test: 0.2
random_seed: 42
# === Processing ===
pubchem_chunksize: 100000 # Rows per chunk for streaming PubChem processing
pubchem_etl:
chunksize: 100000
human_only: true
bindingdb_etl:
chunksize: 100000
inactive_threshold_nm: 10000
human_only: true
# === Confidence Tier Ordering (gold = highest) ===
confidence_tiers:
- gold
- silver
- bronze
- copper
# === Paths (relative to project root) ===
paths:
data_dir: data
exports_dir: exports
migrations_dir: migrations
database: data/negbiodb.db
# === Download URLs ===
downloads:
pubchem:
# Legacy keys kept for backward compatibility
url: "https://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/Extras/bioactivities.tsv.gz"
dest: data/pubchem/bioactivities.tsv.gz
min_size_bytes: 1000000000
# Required files for full PubChem ETL
bioassays_url: "https://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/Extras/bioassays.tsv.gz"
bioassays_dest: data/pubchem/bioassays.tsv.gz
bioassays_min_size_bytes: 10000000
aid_uniprot_url: "https://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/Extras/Aid2GeneidAccessionUniProt.gz"
aid_uniprot_dest: data/pubchem/Aid2GeneidAccessionUniProt.gz
aid_uniprot_min_size_bytes: 1000000
sid_cid_smiles_url: "https://ftp.ncbi.nlm.nih.gov/pubchem/Bioassay/Extras/Sid2CidSMILES.gz"
sid_cid_smiles_dest: data/pubchem/Sid2CidSMILES.gz
sid_cid_smiles_min_size_bytes: 1000000
sid_lookup_db: data/pubchem/sid_lookup.sqlite
chembl:
dest_dir: data/chembl
bindingdb:
servlet_url: "https://www.bindingdb.org/rwd/bind/chemsearch/marvin/SDFdownload.jsp?download_file=/rwd/bind/downloads/BindingDB_All_202603_tsv.zip"
file_url: "https://www.bindingdb.org/rwd/bind/downloads/BindingDB_All_202603_tsv.zip"
dest_dir: data/bindingdb
min_size_bytes: 500000000
davis:
base_url: "https://raw.githubusercontent.com/dingyan20/Davis-Dataset-for-DTA-Prediction/master"
files:
- drugs.csv
- proteins.csv
- drug_protein_affinity.csv
dest_dir: data/davis
min_rows: 25000
# ============================================================
# Clinical Trial Failure Domain
# ============================================================
ct_domain:
# === Paths ===
paths:
database: data/negbiodb_ct.db
migrations_dir: migrations_ct
data_dir: data/ct
# === Downloads ===
downloads:
aact:
# AACT pipe-delimited snapshot; URL changes monthly — update as needed
# Get latest from: https://aact.ctti-clinicaltrials.org/pipe_files
dest_dir: data/ct/aact
required_disk_gb: 6.0
# 13 of 46 AACT tables needed for v1
tables:
- studies
- interventions
- conditions
- outcomes
- outcome_analyses
- outcome_measurements
- designs
- sponsors
- calculated_values
- browse_interventions
- browse_conditions
- drop_withdrawals
- documents
opentargets:
url: "https://huggingface.co/api/datasets/opentargets/clinical_trial_reason_to_stop/parquet/default/train/0000.parquet"
dest: data/ct/opentargets/stop_reasons.parquet
cto:
url: "https://huggingface.co/api/datasets/chufangao/CTO/parquet/human_labels/test/0.parquet"
dest: data/ct/cto/cto_outcomes.parquet
shi_du:
# Figshare: Shi & Du 2024, doi:10.6084/m9.figshare.c.6860254.v1
efficacy_url: "https://ndownloader.figshare.com/files/42520528"
efficacy_dest: data/ct/shi_du/efficacy_df.csv
safety_url: "https://ndownloader.figshare.com/files/42520534"
safety_dest: data/ct/shi_du/safety_df.csv
# === Failure Classification ===
failure_category_precedence:
- safety
- efficacy
- pharmacokinetic
- enrollment
- strategic
- regulatory
- design
- other
# === Drug Name Resolution ===
drug_resolution:
fuzzy_threshold: 0.90
pubchem_rate_limit_per_sec: 5
pubchem_cache: data/ct/pubchem_name_cache.json
overrides_file: data/ct/drug_name_overrides.csv
# === NLP Classifier ===
classifier:
max_features: 10000
ngram_range: [1, 2]
cv_folds: 5
# ============================================================
# Protein-Protein Interaction Negative Domain
# ============================================================
ppi_domain:
# === Paths ===
paths:
database: data/negbiodb_ppi.db
migrations_dir: migrations_ppi
data_dir: data/ppi
# === Downloads ===
downloads:
huri:
hi_union_url: "https://www.interactome-atlas.org/data/HI-union.tsv"
# hi_iii_url removed — HI-III-20.tsv returns 404 as of 2026-03
idmapping_url: "https://ftp.uniprot.org/pub/databases/uniprot/current_release/knowledgebase/idmapping/by_organism/HUMAN_9606_idmapping.dat.gz"
dest_dir: data/ppi/huri
intact:
url: "https://ftp.ebi.ac.uk/pub/databases/intact/current/psimitab/intact_negative.txt"
dest: data/ppi/intact/intact_negative.txt
min_size_bytes: 1000000
humap:
base_url: "https://humap3.proteincomplexes.org/static/downloads/humap3"
neg_train: ComplexPortal_reduced_20230309.neg_train_ppis.txt
neg_test: ComplexPortal_reduced_20230309.neg_test_ppis.txt
pos_train: ComplexPortal_reduced_20230309.train_ppis.txt
pos_test: ComplexPortal_reduced_20230309.test_ppis.txt
dest_dir: data/ppi/humap
string:
links_url: "https://stringdb-downloads.org/download/protein.links.v12.0/9606.protein.links.v12.0.txt.gz"
mapping_url: "https://stringdb-downloads.org/download/mapping_files/uniprot/human.uniprot_2_string.2018.tsv.gz"
dest_dir: data/ppi/string
biogrid:
url: "https://downloads.thebiogrid.org/Download/BioGRID/Latest-Release/BIOGRID-ALL-LATEST.tab3.zip"
dest_dir: data/ppi/biogrid
# === Evidence Type Priority (best first) ===
evidence_type_priority:
- experimental_non_interaction
- literature_reported
- ml_predicted_negative
- low_score_negative
- compartment_separated
# === STRING ETL Settings ===
string_etl:
min_protein_degree: 5
max_negative_pairs: 500000
# === Benchmark Split ===
split_ratios: {train: 0.7, val: 0.1, test: 0.2}
random_seed: 42