act.installer.HMDBParser.java Source code

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/*************************************************************************
*                                                                        *
*  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;
        }
    }
}