/*************************************************************************
* *
* This file is part of the 20n/act project. *
* 20n/act enables DNA prediction for synthetic biology/bioengineering. *
* Copyright (C) 2017 20n Labs, Inc. *
* *
* Please direct all queries to act@20n.com. *
* *
* This program is free software: you can redistribute it and/or modify *
* it under the terms of the GNU General Public License as published by *
* the Free Software Foundation, either version 3 of the License, or *
* (at your option) any later version. *
* *
* This program is distributed in the hope that it will be useful, *
* but WITHOUT ANY WARRANTY; without even the implied warranty of *
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the *
* GNU General Public License for more details. *
* *
* You should have received a copy of the GNU General Public License *
* along with this program. If not, see <http://www.gnu.org/licenses/>. *
* *
*************************************************************************/
package act.installer;
import act.installer.pubchem.PubchemParser;
import act.server.MongoDB;
import act.shared.Chemical;
import org.apache.commons.cli.CommandLine;
import org.apache.commons.cli.CommandLineParser;
import org.apache.commons.cli.DefaultParser;
import org.apache.commons.cli.HelpFormatter;
import org.apache.commons.cli.Option;
import org.apache.commons.cli.Options;
import org.apache.commons.cli.ParseException;
import org.apache.commons.lang3.StringUtils;
import org.apache.commons.lang3.tuple.Triple;
import org.apache.logging.log4j.LogManager;
import org.apache.logging.log4j.Logger;
import org.jaxen.JaxenException;
import org.jaxen.XPath;
import org.jaxen.dom.DOMXPath;
import org.json.JSONArray;
import org.json.JSONException;
import org.json.JSONObject;
import org.w3c.dom.Document;
import org.w3c.dom.Node;
import org.xml.sax.SAXException;
import javax.xml.parsers.DocumentBuilder;
import javax.xml.parsers.DocumentBuilderFactory;
import javax.xml.parsers.ParserConfigurationException;
import java.io.File;
import java.io.IOException;
import java.util.ArrayList;
import java.util.Collections;
import java.util.HashMap;
import java.util.List;
import java.util.Map;
import java.util.SortedSet;
import java.util.TreeSet;
import java.util.regex.Pattern;
import java.util.stream.Collectors;
public class HMDBParser {
private static final Logger LOGGER = LogManager.getFormatterLogger(HMDBParser.class);
private static final String OPTION_INPUT_DIRECTORY = "i";
private static final String OPTION_DB_HOST = "H";
private static final String OPTION_DB_PORT = "p";
private static final String OPTION_DB_NAME = "d";
private static final String DEFAULT_DB_HOST = "localhost";
private static final String DEFAULT_DB_PORT = "27017";
private static final String DEFAULT_DB_NAME = "actv01";
public static final String HELP_MESSAGE = StringUtils.join(new String[]{
"This class parses HMDB XML files, converts them into chemical documents, and stores them in a DB",
}, "");
public static final List<Option.Builder> OPTION_BUILDERS = new ArrayList<Option.Builder>() {{
add(Option.builder(OPTION_INPUT_DIRECTORY)
.argName("input dir")
.desc("The directory where the HMDB XML files live")
.hasArg()
.required()
.longOpt("input-dir")
);
add(Option.builder(OPTION_DB_HOST)
.argName("hostname")
.desc(String.format("The DB host to which to connect (default: %s)", DEFAULT_DB_HOST))
.hasArg()
.longOpt("db-host")
);
add(Option.builder(OPTION_DB_PORT)
.argName("port")
.desc(String.format("The DB port to which to connect (default: %s)", DEFAULT_DB_PORT))
.hasArg()
.longOpt("db-port")
);
add(Option.builder(OPTION_DB_NAME)
.argName("name")
.desc(String.format("The name of the DB to which to install the HMDB chemicals (default: %s)", DEFAULT_DB_NAME))
.hasArg()
.longOpt("db-name")
);
add(Option.builder("h")
.argName("help")
.desc("Prints this help message")
.longOpt("help")
);
}};
public static final HelpFormatter HELP_FORMATTER = new HelpFormatter();
static {
HELP_FORMATTER.setWidth(100);
}
/* HMDB files all have five digits from 1 through 61388 as of the initial writing of this class. I've allowed for an
* extra digit in case the next release of the DB exceeds 100k metabolites. We also log rejected files just in case.
*/
private static final Pattern HMDB_FILE_REGEX = Pattern.compile("^HMDB\\d{5,6}\\.xml$");
/* Represent the HMDB paths as enums to constrain the universe of extracted features to a fixed set of paths.
* Most of the features are not sub-tree dependent, so we can just separate them into TEXT and NODES paths (i.e. paths
* that return a single string or paths that return nodes containing either a string or a sub-tree that needs to be
* re-parsed together). For sub-trees requiring dependent parsing, where one path doesn't do the trick, we use the
* L1/L2 convention adopted in PubchemParser:
* Structure: <feature name>_<level>[_<sub-feature or structure>]_<type>
* L1 extracts a sub-tree, while L2 extracts the features of the sub-tree so they can be linked together.
*
* Note also the description of features we're *not* currently extracting. There are other data in the HMDB entries
* that may be useful at some point, but in the interest of time are being ignored for now. */
private enum HMDB_XPATH {
HMDB_ID_TEXT("/metabolite/accession/text()"),
// Names
PRIMARY_NAME_TEXT("/metabolite/name/text()"),
IUPAC_NAME_TEXT("/metabolite/iupac_name/text()"),
SYNONYMS_NODES("/metabolite/synonyms/synonym"),
// Structures
INCHI_TEXT("/metabolite/inchi/text()"),
SMILES_TEXT("/metabolite/smiles/text()"),
// Ontology
ONTOLOGY_STATUS_TEXT("/metabolite/ontology/status/text()"),
ONTOLOGY_ORIGINS_NODES("/metabolite/ontology/origins/origin"),
ONTOLOGY_FUNCTIONS_NODES("/metabolite/ontology/functions/function"),
ONTOLOGY_APPLICATIONS_NODES("/metabolite/ontology/applications/application"),
ONTOLOGY_LOCATIONS_NODES("/metabolite/ontology/cellular_locations/cellular_location"),
// Physiological locality
LOCATIONS_FLUID_NODES("/metabolite/biofluid_locations/biofluid"),
LOCATIONS_TISSUE_NODES("/metabolite/tissue_locations/tissue"),
// Metabolic pathways
PATHWAY_NAME_NODES("/metabolite/pathways/pathway/name"),
// Diseases
DISEASE_NAME_NODES("/metabolite/diseases/disease/name"),
// External IDs
METLIN_ID_TEXT("/metabolite/metlin_id/text()"),
PUBCHEM_ID_TEXT("/metabolite/pubchem_compound_id/text()"),
CHEBI_ID_TEXT("/metabolite/chebi_id/text()"),
// Proteins
PROTEIN_L1_NODES("/metabolite/protein_associations/protein"),
PROTEIN_L2_NAME_TEXT("/protein/name/text()"),
PROTEIN_L2_UNIPROT_ID_TEXT("/protein/uniprot_id/text()"),
PROTEIN_L2_GENE_NAME_TEXT("/protein/gene_name/text()"),
/* Features we're not extracting right now:
* * Normal/abnormal concentrations in different fluids/tissues (too many different kinds of expression/units)
* * Experimentally derived and predicted properties (many of the latter come from Chemaxon anyway)
* * "specdb" ids, which represent NRM/MS2 data out there, not sure how useful this is right now
* * Pathway details and ids, which hopefully are already captured via Metacyc
* * Literature references, which we'd only inspect manually at present and we can always return to the source
*/
;
String path;
HMDB_XPATH(String path) {
this.path = path;
}
public String getPath() {
return path;
}
// We rely on Jaxen because we've experienced performance problems using the built-in/xerces XPath implementation.
DOMXPath compile() throws JaxenException {
return new DOMXPath(this.getPath());
}
}
public static void main(String[] args) throws Exception {
// Parse the command line options
Options opts = new Options();
for (Option.Builder b : OPTION_BUILDERS) {
opts.addOption(b.build());
}
CommandLine cl = null;
try {
CommandLineParser parser = new DefaultParser();
cl = parser.parse(opts, args);
} catch (ParseException e) {
System.err.format("Argument parsing failed: %s\n", e.getMessage());
HELP_FORMATTER.printHelp(PubchemParser.class.getCanonicalName(), HELP_MESSAGE, opts, null, true);
System.exit(1);
}
if (cl.hasOption("help")) {
HELP_FORMATTER.printHelp(PubchemParser.class.getCanonicalName(), HELP_MESSAGE, opts, null, true);
return;
}
File inputDir = new File(cl.getOptionValue(OPTION_INPUT_DIRECTORY));
if (!inputDir.isDirectory()) {
System.err.format("Input directory at %s is not a directory\n", inputDir.getAbsolutePath());
System.exit(1);
}
String dbName = cl.getOptionValue(OPTION_DB_NAME, DEFAULT_DB_NAME);
String dbHost = cl.getOptionValue(OPTION_DB_HOST, DEFAULT_DB_HOST);
Integer dbPort = Integer.valueOf(cl.getOptionValue(OPTION_DB_PORT, DEFAULT_DB_PORT));
LOGGER.info("Connecting to %s:%d/%s", dbHost, dbPort, dbName);
MongoDB db = new MongoDB(dbHost, dbPort, dbName);
HMDBParser parser = Factory.makeParser(db);
LOGGER.info("Starting parser");
parser.run(inputDir);
LOGGER.info("Done");
}
private final Map<HMDB_XPATH, XPath> xpaths = new HashMap<>();
private MongoDB db;
// This is required for extracting locality-dependent features of sub-trees using XPath.
private DocumentBuilder documentBuilder;
protected HMDBParser(MongoDB db) {
this.db = db;
}
protected void init() throws JaxenException, ParserConfigurationException {
for (HMDB_XPATH xpath : HMDB_XPATH.values()) {
xpaths.put(xpath, xpath.compile());
}
// This bit pilfered from PubchemParser.java.
// TODO: next time we use this, put it in a common super class (do it once, do it again, then do it right!).
DocumentBuilderFactory factory = DocumentBuilderFactory.newInstance();
documentBuilder = factory.newDocumentBuilder();
}
// TODO: add some constraints on HMDB_XPATHs that allow us to programmatically check they're being applied correctly.
/**
* Get the text contents contained in a list of nodes. Used for multi-valued fields that are siblings in the tree.
* @param n A list of nodes whose text content should be extracted.
* @return The text for each node.
*/
private static List<String> extractNodesText(List<Node> n) {
return n.stream().map(Node::getTextContent).collect(Collectors.toList());
}
private List<Node> getNodes(HMDB_XPATH xpath, Document doc) throws JaxenException {
return (List<Node>) xpaths.get(xpath).selectNodes(doc); // No check, but guaranteed to return List<Node>.
}
/**
* Extract the textual content for a set of sibling nodes appearing at some path in the specified document.
* @param xpath The path to use as a query.
* @param doc The document to query.
* @return The textual content of the nodes that live at the specified path.
* @throws JaxenException
*/
private List<String> getTextFromNodes(HMDB_XPATH xpath, Document doc) throws JaxenException {
return extractNodesText(getNodes(xpath, doc));
}
private String getText(HMDB_XPATH xpath, Document doc) throws JaxenException {
return xpaths.get(xpath).stringValueOf(doc);
}
/**
* Convert an HMDB XML document into a Chemical object. Expects one chemical per document.
* @param doc A parsed HMDB XML doc.
* @return The corresponding chemical to store in the DB.
* @throws JaxenException
* @throws JSONException
*/
protected Chemical extractChemicalFromXMLDocument(Document doc) throws JaxenException, JSONException {
String hmdbId = getText(HMDB_XPATH.HMDB_ID_TEXT, doc);
String primaryName = getText(HMDB_XPATH.PRIMARY_NAME_TEXT, doc);
String iupacName = getText(HMDB_XPATH.IUPAC_NAME_TEXT, doc);
List<String> synonyms = getTextFromNodes(HMDB_XPATH.SYNONYMS_NODES, doc);
String inchi = getText(HMDB_XPATH.INCHI_TEXT, doc);
String smiles = getText(HMDB_XPATH.SMILES_TEXT, doc);
// Require an InChI if we're going to consume this molecule.
if (inchi == null || inchi.isEmpty()) {
LOGGER.warn("No InChI found for HMDB chemical %s, aborting", hmdbId);
return null;
}
String ontologyStatus = getText(HMDB_XPATH.ONTOLOGY_STATUS_TEXT, doc);
List<String> ontologyOrigins = getTextFromNodes(HMDB_XPATH.ONTOLOGY_ORIGINS_NODES, doc);
List<String> ontologyFunctions = getTextFromNodes(HMDB_XPATH.ONTOLOGY_FUNCTIONS_NODES, doc);
List<String> ontologyApplications = getTextFromNodes(HMDB_XPATH.ONTOLOGY_APPLICATIONS_NODES, doc);
List<String> ontologyLocations = getTextFromNodes(HMDB_XPATH.ONTOLOGY_LOCATIONS_NODES, doc);
List<String> locationFluids = getTextFromNodes(HMDB_XPATH.LOCATIONS_FLUID_NODES, doc);
List<String> locationTissues = getTextFromNodes(HMDB_XPATH.LOCATIONS_TISSUE_NODES, doc);
List<String> pathwayNames = getTextFromNodes(HMDB_XPATH.PATHWAY_NAME_NODES, doc);
List<String> diseaseNames = getTextFromNodes(HMDB_XPATH.DISEASE_NAME_NODES, doc);
String metlinId = getText(HMDB_XPATH.METLIN_ID_TEXT, doc);
String pubchemId = getText(HMDB_XPATH.PUBCHEM_ID_TEXT, doc);
String chebiId = getText(HMDB_XPATH.CHEBI_ID_TEXT, doc);
List<Node> proteins = getNodes(HMDB_XPATH.PROTEIN_L1_NODES, doc);
// Simple triples of name, uniprot id, gene name.
List<Triple<String, String, String>> proteinAttributes = new ArrayList<>(proteins.size());
for (Node n : proteins) {
/* In order to run XPath on a sub-document, we have to Extract the relevant nodes into their own document object.
* If we try to run evaluate on `n` instead of this new document, we'll get matching paths for the original
* document `d` but not for the nodes we're looking at right now. Very weird. */
Document proteinDoc = documentBuilder.newDocument();
proteinDoc.adoptNode(n);
proteinDoc.appendChild(n);
String name = getText(HMDB_XPATH.PROTEIN_L2_NAME_TEXT, proteinDoc);
String uniprotId = getText(HMDB_XPATH.PROTEIN_L2_UNIPROT_ID_TEXT, proteinDoc);
String geneName = getText(HMDB_XPATH.PROTEIN_L2_GENE_NAME_TEXT, proteinDoc);
proteinAttributes.add(Triple.of(name, uniprotId, geneName));
}
// Assumption: when we reach this point there will always be an InChI.
Chemical chem = new Chemical(inchi);
chem.setSmiles(smiles);
chem.setCanon(primaryName);
if (pubchemId != null && !pubchemId.isEmpty()) {
chem.setPubchem(Long.valueOf(pubchemId));
}
synonyms.forEach(chem::addSynonym);
chem.addSynonym(iupacName); // TODO: is there a better place for this?
JSONObject meta = new JSONObject()
.put("hmdb_id", hmdbId)
.put("ontology", new JSONObject()
.put("status", ontologyStatus)
.put("origins", new JSONArray(ontologyOrigins))
.put("functions", new JSONArray(ontologyFunctions))
.put("applications", new JSONArray(ontologyApplications))
.put("locations", new JSONArray(ontologyLocations))
)
.put("location", new JSONObject()
.put("fluid", new JSONArray(locationFluids))
.put("tissue", new JSONArray(locationTissues))
)
.put("pathway_names", new JSONArray(pathwayNames))
.put("disease_names", new JSONArray(diseaseNames))
.put("metlin_id", metlinId)
.put("chebi_id", chebiId)
.put("proteins", new JSONArray(proteinAttributes.stream()
.map(t -> new JSONObject().
put("name", t.getLeft()).
put("uniprot_id", t.getMiddle()).
put("gene_name", t.getRight())
).collect(Collectors.toList())
)
);
chem.putRef(Chemical.REFS.HMDB, meta);
return chem;
}
protected SortedSet<File> findHMDBFilesInDirectory(File dir) throws IOException {
// Sort for consistency + sanity.
SortedSet<File> results = new TreeSet<>((a, b) -> a.getName().compareTo(b.getName()));
for (File file : dir.listFiles()) { // Do our own filtering so we can log rejects, of which we expect very few.
if (HMDB_FILE_REGEX.matcher(file.getName()).matches()) {
results.add(file);
} else {
LOGGER.warn("Found non-conforming HMDB file in directory %s: %s", dir.getAbsolutePath(), file.getName());
}
}
return results;
}
/**
* Extract all chemicals from HMDB XML files that live in the specified directory and save them in the DB.
* Note that this search is not recursive: documents in sub-directories will be ignored.
* @param inputDir The directory to scan for HMDB XML files.
* @throws IOException
* @throws IllegalArgumentException
*/
public void run(File inputDir) throws IOException, IllegalArgumentException {
if (inputDir == null || !inputDir.isDirectory()) {
String msg = String.format("Unable to read input directory at %s",
inputDir == null ? "null" : inputDir.getAbsolutePath());
LOGGER.error(msg);
throw new RuntimeException(msg);
}
SortedSet<File> files = findHMDBFilesInDirectory(inputDir);
LOGGER.info("Found %d HMDB XML files in directory %s", files.size(), inputDir.getAbsolutePath());
for (File file : files) {
LOGGER.debug("Processing HMDB XML file %s", file.getAbsolutePath());
/* Promote our XML-specific exceptions to generic IllegalArgumentExceptions to reduce error handling surface
* area for the caller. */
Document d;
try {
d = documentBuilder.parse(file);
} catch (SAXException e) {
String msg = String.format("Unable to parse XML file at %s: %s", file.getAbsolutePath(), e.getMessage());
throw new IllegalArgumentException(msg, e);
}
/* Jaxen doesn't throw exceptions if it can't find a path, so a JaxenException here is completely unexpected.
* It might mean corrupted XML or some unrecoverable XPath problem that we don't expect. In any case, promote
* the exception to the caller as it's unclear how we could deal with such an error here. */
Chemical chem;
try {
chem = extractChemicalFromXMLDocument(d);
} catch (JaxenException e) {
String msg = String.format("Unable to extract features from XML file at %s: %s",
file.getAbsolutePath(), e.getMessage());
throw new IllegalArgumentException(msg, e);
}
// Not all HMDB entries contain
if (chem == null) {
LOGGER.warn("Unable to create chemical from file %s", file.getAbsolutePath());
continue;
}
// submitToActChemicalDB creates or merges as necessary.
Long id = db.getNextAvailableChemicalDBid();
db.submitToActChemicalDB(chem, id);
LOGGER.debug("Submitted chemical %d to the DB", id);
}
LOGGER.info("Loaded %d HMDB chemicals into DB", files.size());
}
public static class Factory {
public static HMDBParser makeParser(MongoDB db) {
HMDBParser parser = new HMDBParser(db);
// Promote XML-specific exceptions from parser initialization to runtime exceptions, as they are definite bugs.
try {
parser.init();
} catch (JaxenException e) {
LOGGER.error("BUG: caught JaxenException on initialization, which means programmer error: %s",
e.getMessage());
throw new RuntimeException(e);
} catch (ParserConfigurationException e) {
LOGGER.error("BUG: caught ParserConfigurationException on initialization, which means programmer error: %s",
e.getMessage());
throw new RuntimeException(e);
}
return parser;
}
}
}