README

extractox is a comprehensive R package designed to simplify querying various chemical, toxicological, and biological databases such as the Comparative Toxicogenomics Database (CTP) of the MDI Biological Laboratory and NC State University, the Integrated Chemical Environment (ICE) of the National Toxicology Program (NTP), the Integrated Risk Information System (IRIS) of the Environmental Protection Agency (EPA), the CompTox Chemicals Dashboard Resource Hub (CompTox) of EPA, and PubChem of the National Center for Biotechnology Information/National Institures Of Health (NCBI, NIH). The package facilitates interaction with APIs, providing curated and user-friendly outputs.

Installation

# From CRAN
install.packages("extractox")

Development Version

To get a bug fix or to use a feature from the development version, you can install the development version of extractox from GitHub.

# Install pak if not already installed
if (!requireNamespace("pak", quietly = TRUE)) {
  install.packages("pak")
}

# Install the package from GitHub
pak::pkg_install("c1au6i0/extractox")

Features

ICE Database

The ICE database, managed by the EPA, provides access to a variety of data related to chemical toxicity, exposure, and risk assessment. It includes data from high-throughput screening assays, in vivo studies, and computational models.

extr_ice provides access to NTP’s ICE database for toxicological and exposure-related data.

library(extractox)
ice_data <- extr_ice(casrn = c("50-00-0"), assays = NULL) # assays is null so all assays are retrieved
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Sending request to ICE database...
#> Request succeeded with status code: 200
names(ice_data)
#>  [1] "assay"              "endpoint"           "substanceType"     
#>  [4] "casrn"              "qsarReadyId"        "value"             
#>  [7] "unit"               "species"            "receptorSpecies"   
#> [10] "route"              "sex"                "strain"            
#> [13] "lifeStage"          "tissue"             "lesion"            
#> [16] "location"           "assaySource"        "inVitroAssayFormat"
#> [19] "reference"          "referenceUrl"       "dtxsid"            
#> [22] "substanceName"      "pubMedId"

IRIS

The IRIS database is managed by the EPA and contains information on the health effects of exposure to various substances found in the environment. It provides qualitative and quantitative health risk information.

extr_iris provides access to EPA’s IRIS database and accepts queries of Chemical Abstracts Service Registry Number (CASRN) or International Union of Pure and Applied Chemistry (IUPAC) names of chemicals.

iris_info <- extr_iris(c("glyphosate", "50-00-0"))
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Quering glyphosate to EPA IRIS database...
#> Request succeeded with status code: 200
#> Quering 50-00-0 to EPA IRIS database...
#> Request succeeded with status code: 200
names(iris_info)
#> [1] "chemical_name"                 "casrn"                        
#> [3] "exposure_route"                "assessment_type"              
#> [5] "critical_effect_or_tumor_type" "woe_characterization"         
#> [7] "toxicity_value_type"           "toxicity_value"

CompTox

The CompTox Chemistry Dashboard, managed by the EPA, provides access to data on chemical structures, properties, and associated bioactivity data. It integrates data from various sources to support chemical safety assessments.

extr_comptox extracts data from the CompTox Chemistry Dashboard using both CASRN and IUPAC names of chemicals and returns a list of dataframes.

info_comptox <- extr_comptox(ids = c("Aspirin", "50-00-0"))
#> ℹ Sending request to CompTox...
#> Request succeeded with status code: 202
#> ℹ Getting info from CompTox...
#> 
#> Request succeeded with status code: 200
names(info_comptox)
#> [1] "comptox_cover_sheet"           "comptox_main_data"            
#> [3] "comptox_abstract_sifter"       "comptox_synonym_identifier"   
#> [5] "comptox_related_relationships" "comptox_toxcast_assays_ac50"  
#> [7] "comptox_toxval_details"        "comptox_chemical_properties"

Tox Info

The function extr_tox is a wrapper used to call all the above-mentioned functions and retrieve a list of dataframes.

info_tox <- extr_tox(casrn = c("Aspirin", "50-00-0"))
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> ℹ Getting PubChem IDS...
#> Querying Aspirin. OK (HTTP 200).
#> Querying 2244. OK (HTTP 200).
#> ℹ Getting PubChem IDS...
#> Querying 50-00-0. OK (HTTP 200).
#> Querying 712. OK (HTTP 200).
#> ℹ Sending request to CompTox...
#> Request succeeded with status code: 202ℹ Getting info from CompTox...
#> Request succeeded with status code: 200ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Sending request to ICE database...Request succeeded with status code: 200ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Quering Aspirin to EPA IRIS database...Request succeeded with status code: 200Quering 50-00-0 to EPA IRIS database...Request succeeded with status code: 200

CTD Database

The CTP provides information about the interactions between chemicals, genes, and diseases. It helps in understanding the effects of environmental exposures on human health.

extr_ctd extracts information related to chemical-gene or pathway associations.

input_terms <- c("50-00-0", "64-17-5", "methanal", "ethanol")
ctd_association <- extr_ctd(
  input_terms = input_terms,
  category = "chem",
  report_type = "genes_curated",
  input_term_search_type = "directAssociations",
  action_types = "ANY",
  ontology = c("go_bp", "go_cc")
)
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Sending request to CTD database...
#> Request succeeded with status code: 200


# Get expresssion data
ctd_expression <- extr_ctd(
  input_terms = input_terms,
  report_type = "cgixns",
  category = "chem",
  action_types = "expression"
)
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Sending request to CTD database...Request succeeded with status code: 200

names(ctd_expression)
#>  [1] "x_input"             "chemical_name"       "chemical_id"        
#>  [4] "cas_rn"              "gene_symbol"         "gene_id"            
#>  [7] "organism"            "organism_id"         "interaction"        
#> [10] "interaction_actions" "pub_med_i_ds"

Tetramers are computationally generated information units that interrelate four data types from the CTP: a chemical, gene product, phenotype, and disease. They help in understanding the complex relationships between these entities and their combined impact on human health.

tetramer_data <- extr_tetramer(
  chem = c("50-00-0", "ethanol"),
  disease = "",
  gene = "",
  go = "",
  input_term_search_type = "directAssociations",
  qt_match_type = "equals"
)
#> Sending request to CTD database for tetramer data for 50-00-0...
#> Request succeeded with status code: 200
#> Sending request to CTD database for tetramer data for ethanol...
#> Request succeeded with status code: 200

names(tetramer_data)
#> [1] "query"        "chemical"     "chemical_id"  "gene"         "gene_id"     
#> [6] "phenotype"    "phenotype_id" "disease"      "disease_id"

PubChem Database

PubChem is an open chemistry database at the NIH. It provides information on chemical structures, identifiers, chemical and physical properties, biological activities, safety and toxicity information, patents, literature citations, and more.

A series of functions that rely on the webchem package are used to extract chemical information, Globally Harmonized System (GHS) classification data, or flavor classification from PubChem.

The function extr_chem_info retrieves chemical information of IUPAC-named chemicals. A warning is displayed if the chemical is not found.

chem_info <- extr_chem_info(IUPAC_names = c("Formaldehyde", "Aflatoxin B1"))
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Querying Formaldehyde. OK (HTTP 200).
#> Querying Aflatoxin B1. OK (HTTP 200).
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> ℹ Querying 712 and 186907.
names(chem_info)
#>  [1] "cid"                         "iupac_name"                 
#>  [3] "cas_rn"                      "cid_all"                    
#>  [5] "cas_rn_all"                  "molecular_formula"          
#>  [7] "molecular_weight"            "canonical_smiles"           
#>  [9] "isomeric_smiles"             "in_ch_i"                    
#> [11] "in_ch_i_key"                 "iupac_name_y"               
#> [13] "x_log_p"                     "exact_mass"                 
#> [15] "monoisotopic_mass"           "tpsa"                       
#> [17] "complexity"                  "charge"                     
#> [19] "h_bond_donor_count"          "h_bond_acceptor_count"      
#> [21] "rotatable_bond_count"        "heavy_atom_count"           
#> [23] "isotope_atom_count"          "atom_stereo_count"          
#> [25] "defined_atom_stereo_count"   "undefined_atom_stereo_count"
#> [27] "bond_stereo_count"           "defined_bond_stereo_count"  
#> [29] "undefined_bond_stereo_count" "covalent_unit_count"        
#> [31] "volume3d"                    "x_steric_quadrupole3d"      
#> [33] "y_steric_quadrupole3d"       "z_steric_quadrupole3d"      
#> [35] "feature_count3d"             "feature_acceptor_count3d"   
#> [37] "feature_donor_count3d"       "feature_anion_count3d"      
#> [39] "feature_cation_count3d"      "feature_ring_count3d"       
#> [41] "feature_hydrophobe_count3d"  "conformer_model_rmsd3d"     
#> [43] "effective_rotor_count3d"     "conformer_count3d"          
#> [45] "fingerprint2d"               "query"

Two functions are used to extract specific sections of PubChem chemical information using CASRN:

ghs_info <- extr_pubchem_ghs(casrn = c("50-00-0", "64-17-5"))
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> ℹ Getting PubChem IDS...
#> Querying 50-00-0. OK (HTTP 200).
#> Querying 712. OK (HTTP 200).
#> ℹ Getting PubChem IDS...
#> Querying 64-17-5. OK (HTTP 200).
#> Querying 702. OK (HTTP 200).
fema_info <- extr_pubchem_fema(casrn = c("50-00-0", "123-68-2"))
#> ℹ Checking Internet Connection...
#> ℹ Internet connection OK...
#> Querying 50-00-0. OK (HTTP 200).
#> Querying 712. Not Found (HTTP 404).
#> ℹ FEMA for 50-00-0 not found!
#> Querying 123-68-2. OK (HTTP 200).
#> Querying 31266. OK (HTTP 200).

Important Note for Linux Users

Please note that functions that pull data from EPA servers may encounter issues on some Linux systems. This is because these servers do not accept secure legacy renegotiation. On Linux system, those functions depend on curl and OpenSSL, which have known problems with unsafe legacy renegotiation in newer versions. One workaround is to downgrade to curl v7.78.0 and OpenSSL v1.1.1. However, please be aware that using these older versions might introduce potential security vulnerabilities. Refer to this gist for instructions on how to downgrade curl and OpenSSL on Ubuntu.