Source

orange-bioinformatics / _bioinformatics / obiPPI.py

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"""\
Protein-protein interactions
============================

This is python module for accessing PPI data.  
"""

from __future__ import absolute_import

import collections, gzip, posixpath, os, shutil, sqlite3, sys, urllib2, warnings, xml.dom.minidom as minidom
from collections import defaultdict
from operator import itemgetter

from Orange.orng import orngServerFiles
from Orange.utils import ConsoleProgressBar, lru_cache

from . import obiTaxonomy

from .obiTaxonomy import pickled_cache

class PPIDatabase(object):
    """ A general interface for protein-protein interaction database access.
    
    An example useage::
        >>> ppidb = MySuperPPIDatabase()
        >>> ppidb.organisms() # List all organisms (taxids)
        ['...
        
        >>> ppidb.ids() # List all protein ids
        ['...
        
        >>> ppidb.ids(taxid="9606") # List all human protein ids.
        ['...
        
        >>> ppidb.links() # List all links 
        [('...
    """
    def __init__(self):
        pass
    
    def organisms(self):
        """ Return all organism taxids contained in this database.
        """
        raise NotImplementedError
    
    def ids(self, taxid=None):
        """ Return a list of all protein ids. If `taxid` is not None limit
        the results to ids from this organism only.
        
        """
        raise NotImplementedError
    
    def synonyms(self, id):
        """ Return a list of synonyms for primary `id`.
        """
        raise NotImplementedError
    
    def all_edges(self, taxid=None):
        """ Return a list of all edges. If taxid is not None return the
        edges for this organism only. 
        
        """
        raise NotImplementedError
    
    def edges(self, id1, id2=None):
        """ Return a list of all edges (a list of 3-tuples (id1, id2, score)).
        """
        raise NotImplementedError
    
    def all_edges_annotated(self, taxid=None):
        """ Return a list of all edges annotated. If taxid is not None
        return the edges for this organism only.
        
        """
        res = []
        for id in self.ids(taxid):
            res.extend(self.edges_annotated(id))
        return res
        
    def edges_annotated(self, id=None):
        """ Return a list of all edges annotated
        """
        raise NotImplementedError
     
    def search_id(self, name, taxid=None):
        """ Search the database for protein name. Return a list of matching 
        primary ids. Use `taxid` to limit the results to a single organism.
         
        """
        raise NotImplementedError
    
    def extract_network(self, ids):
        """
        """
        from Orange import network
        
        graph = network.Graph()
        for id in ids:
            graph.add_node(id, synonyms=",".join(self.synonyms(id)))
            
        for id in ids:
            edges = self.edges(id)
            
            for id1, id2, score in edges:
                graph.add_edge(id1, id2, weight=score)
                
        return graph
        
    
    @classmethod
    def download_data(self):
        """ Download the latest PPI data for local work.
        """
        raise NotImplementedError
    
class BioGRID(PPIDatabase):
    """ Access `BioGRID <http://thebiogrid.org>`_ PPI data.
    
    Example ::
    
        >>> biogrid = BioGRID()
        >>> print biogrid.organism() # Print a list of all organism ncbi taxis in BioGRID
        [u'10090',...
        
        >>> print biogrid.ids(taxid="9606") # Print a set of all human protein ids
        [u'110004'
        
        >>> print biogrid.synonyms("110004") # Print a list of all synonyms for protein id '110004' as reported by BioGRID
        [u'3803', u'CU464060.2', u'CD158b', u'p58.2', u'CD158B1', u'NKAT6']
        
        >>> 
        
    """
    
    SCHEMA = [("links", """\
        biogrid_interaction_id text, 
        biogrid_id_interactor_a text,
        biogrid_id_interactor_b text,
        experimental_system text,
        experimental_system_type text,
        author text,
        pubmed_id text,
        throughput text,
        score real,
        modification text,
        phenotypes text,
        qualifications text,
        tags text,
        source_database text
        """),
            ("proteins", """\
        biogrid_id_interactor text,
        entrez_gene_interactor text,
        systematic_name_interactor text,
        official_symbol_interactor text,
        synonyms_interactor text,
        organism_interactor text,
        """)]
    VERSION = "2.0"
    
    # All column names in the tab2 table. 
    FIELDS = ['biogrid_interaction_id',
              'entrez_gene_interactor_a',
              'entrez_gene_interactor_b',
              'biogrid_id_interactor_a',
              'biogrid_id_interactor_b',
              'systematic_name_interactor_a',
              'systematic_name_interactor_b',
              'official_symbol_interactor_a',
              'official_symbol_interactor_b',
              'synonyms_interactor_a',
              'synonyms_interactor_b',
              'experimental_system',
              'experimental_system_type',
              'author',
              'pubmed_id',
              'organism_interactor_a',
              'organism_interactor_b',
              'throughput',
              'score',
              'modification',
              'phenotypes',
              'qualifications',
              'tags',
              'source_database'
              ]
    
#    BioGRIDInteraction = collections.namedtuple("BioGRIDInteraction", " ".join(SCHEMA[0][1]))
#    BioGRIDInteractor = collections.namedtuple("BioGRIDInteractor", " ".join(SCHEMA[1][1]))
    
    DOMAIN = "PPI"
    SERVER_FILE = "BIOGRID-ALL.sqlite"
    
    def __init__(self):
        self.filename = orngServerFiles.localpath_download(self.DOMAIN, self.SERVER_FILE)
#        info = orngServerFiles.info(self.DOMAIN, self.SERVER_FILE)
        # assert version matches
        self.db = sqlite3.connect(self.filename)
        self.init_db_index()

    @lru_cache(1)
    def organisms(self):
        cur = self.db.execute("select distinct organism_interactor from proteins")
        return cur.fetchall()

    @lru_cache(3)
    def ids(self, taxid=None):
        """ Return a list of all protein ids (biogrid_id_interactors).
        If `taxid` is not None limit the results to ids from this organism
        only.
        
        """
        if taxid is None:
            cur = self.db.execute("""\
                select biogrid_id_interactor
                from proteins""")
        else:
            cur = self.db.execute("""\
                select biogrid_id_interactor
                from proteins
                where organism_interactor=?""", (taxid,))
        
        return [t[0] for t in cur.fetchall()]

    def synonyms(self, id):
        """ Return a list of synonyms for primary `id`.
        
        """
        cur = self.db.execute("""\
            select entrez_gene_interactor,
                   systematic_name_interactor,
                   official_symbol_interactor,
                   synonyms_interactor
            from proteins
            where biogrid_id_interactor=?
            """, (id,))
        rec = cur.fetchone()
        if rec:
            synonyms = list(rec[:-1]) + (rec[-1].split("|") if rec[-1] is not None else [])
            return [s for s in synonyms if s is not None]
        else:
            return []
    
    def all_edges(self, taxid=None):
        """ Return a list of all edges. If taxid is not None return the
        edges for this organism only. 
        
        """
        if taxid is not None:
            cur = self.db.execute("""\
                select biogrid_id_interactor_a, biogrid_id_interactor_a, score
                from links left join proteins on 
                    biogrid_id_interactor_a=biogrid_id_interactor or
                    biogrid_id_interactor_b=biogrid_id_interactor
                where organism_interactor=?
            """, (taxid,))
        else:
            cur = self.db.execute("""\
                select biogrid_id_interactor_a, biogrid_id_interactor_a, score
                from links
            """)
        edges = cur.fetchall()
        return edges
            
    def edges(self, id):
        """ Return a list of all interactions where id is a participant
        (a list of 3-tuples (id_a, id_b, score)).
        
        """
        
        cur = self.db.execute("""\
            select biogrid_id_interactor_a, biogrid_id_interactor_b, score
            from links
            where biogrid_id_interactor_a=? or biogrid_id_interactor_b=?
        """, (id, id))
        return cur.fetchall() 
        
    def all_edges_annotated(self, taxid=None):
        """ Return a list of all edges annotated. If taxid is not None
        return the edges for this organism only.
        
        """
        if taxid is not None:
            cur = self.db.execute("""\
                select *
                from links left join proteins on 
                    biogrid_id_interactor_a=biogrid_id_interactor or
                    biogrid_id_interactor_b=biogrid_id_interactor
                where organism_interactor=?
            """, (taxid,))
        else:
            cur = self.db.execute("""\
                select *
                from links
            """)
        edges = cur.fetchall()
        return edges
        
        
    def edges_annotated(self, id):
        """ Return a list of all links
        """
        cur = self.db.execute("""\
            select *
            from links
            where biogrid_id_interactor_a=? or biogrid_id_interactor_b=?
        """, (id, id))
        return cur.fetchall()
    
    def search_id(self, name, taxid=None):
        """ Search the database for protein name. Return a list of matching 
        primary ids. Use `taxid` to limit the results to a single organism.
         
        """
        # TODO: synonyms_interactor can contain multiple synonyms
        # (should create an indexed table of synonyms)
        if taxid is None:
            cur = self.db.execute("""\
                select biogrid_id_interactor
                from proteins
                where (biogrid_id_interactor=? or
                       entrez_gene_interactor=? or
                       systematic_name_interactor=? or
                       official_symbol_interactor=? or
                       synonyms_interactor=?)
            """, ((name,) * 5))
        else:
            cur = self.db.execute("""\
                select biogrid_id_interactor
                from proteins
                where (biogrid_id_interactor=? or
                       entrez_gene_interactor=? or
                       systematic_name_interactor=? or
                       official_symbol_interactor=? or
                       synonyms_interactor=?)
                      and organism_interactor=? 
            """, ((name,) * 5) + (taxid,))
        res = map(itemgetter(0), cur)
        return res 
    
    @classmethod
    def download_data(cls, address):
        """ Pass the address of the latest release (the tab2 format).
        """
        import urllib2, shutil, zipfile
        from StringIO import StringIO
        stream = urllib2.urlopen(address)
        stream = StringIO(stream.read())
        file = zipfile.ZipFile(stream)
        filename = file.namelist()[0]
        ppi_dir = orngServerFiles.localpath("PPI")
        file.extract(filename, ppi_dir)
        shutil.move(orngServerFiles.localpath("PPI", filename),
                    orngServerFiles.localpath("PPI", "BIOGRID-ALL.tab2"))
        filepath = orngServerFiles.localpath("PPI", "BIOGRID-ALL.tab2")
        cls.init_db(filepath)
        shutil.remove(filepath)
        
    @classmethod
    def init_db(cls, filepath):
        """ Initialize the sqlite data base from a BIOGRID-ALL.*tab2.txt file
        format.
        
        """
        dirname = os.path.dirname(filepath)
        lineiter = iter(open(filepath, "rb"))
        headers = lineiter.next() # read the first line
        
        con = sqlite3.connect(os.path.join(dirname, "BIOGRID-ALL.sqlite"))
        con.execute("drop table if exists links") # Drop old table
        con.execute("drop table if exists proteins") # Drop old table
        
        con.execute("""\
            create table links (
                biogrid_interaction_id text, 
                biogrid_id_interactor_a text,
                biogrid_id_interactor_b text,
                experimental_system text,
                experimental_system_type text,
                author text,
                pubmed_id text,
                throughput text,
                score real,
                modification text,
                phenotypes text,
                qualifications text,
                tags text,
                source_database text
            )""")
        
        con.execute("""\
            create table proteins (
                biogrid_id_interactor text,
                entrez_gene_interactor text,
                systematic_name_interactor text,
                official_symbol_interactor text,
                synonyms_interactor text,
                organism_interactor text
            )""")
        
        proteins = {}
        nulls = lambda values: [val if val != "-" else None for val in values]
        link_indices = [0, 3, 4, 11, 12, 13, 14, 17, 18, 19, 20, 21, 22, 23] # Values that go in the links table
        interactor_a_indices = [3, 1, 5, 7, 9, 15] # Values that go in the proteins table
        interactor_b_indices = [4, 2, 6, 8, 10, 16] # Values that go in the proteins table
        
        def processlinks(file):
            for line in file:
                if line != "\n":
                    fields = nulls(line.strip().split("\t"))
                    yield [fields[i] for i in link_indices]
                    interactor_a = [fields[i] for i in interactor_a_indices]
                    interactor_b = [fields[i] for i in interactor_b_indices]
                    proteins[interactor_a[0]] = interactor_a
                    proteins[interactor_b[0]] = interactor_b
        
        con.executemany("""\
            insert into links values (?, ?, ?, ?, ?, ?, ?, ?, ?, ?, ?, ?, ?, ?)
            """, processlinks(lineiter))
        
        con.executemany("""\
            insert into proteins values (?, ?, ?, ?, ?, ?)
            """, proteins.itervalues())
        con.commit()
        con.close()
        
    def init_db_index(self):
        """ Will create an indexes (if not already pressent) in the database
        for faster searching by primary ids.
        
        """
        self.db.execute("""\
        create index if not exists index_on_biogrid_id_interactor_a
           on links (biogrid_id_interactor_a)
        """)
        self.db.execute("""\
        create index if not exists index_on_biogrid_id_interactor_b
           on links (biogrid_id_interactor_b)
        """)
        self.db.execute("""\
        create index if not exists index_on_biogrid_id_interactor
           on proteins (biogrid_id_interactor)
        """)
        
from collections import namedtuple
from functools import partial

from .obiGeneMania import wget, copyfileobj

def chainiter(iterable):
    for sub_iter in iterable:
        for obj in sub_iter:
            yield obj

def chunks(iter, chunk_size=1000):
    chunk = []
    i = 0
    for obj in iter:
        chunk.append(obj)
        if len(chunk) == chunk_size:
            yield chunk
            chunk = []
    if chunk:
        # The remaining items if any
        yield chunk
    
STRINGInteraction = namedtuple("STRINGInteraciton",
        ["protein_id1", "protein_id2", "combined_score", "mode",
         "action", "score"])

class STRING(PPIDatabase):
    """ Access `STRING <http://www.string-db.org/>`_ PPI database.
    """
    
    DATABASE_SCHEMA = """\
    Database schema
    ---------------
    table `links`:
        - `protein_id1`: id (text)
        - `protein_id2`: id (text)
        - `score`: combined score (int)
        
    table `actions`:
        - `protein_id1`: id (text)
        - `protein_id2`: id (text)
        - `mode`: mode (text)
        - `action`: action type (text)
        - `score`: action score (int)
        
    table `proteins`:
        - `protein_id`: protein id in STRING (text) (in the form of {taxid}.{name})
        - `taxid`: organism taxid (text)
        
    table `aliases`:
        - `protein_id: id (text)
        - `alias`: protein alias (text)
        - `source`: protein alias source (text)
        
    """
    DOMAIN = "PPI"
    FILENAME = "string-protein.sqlite"
    VERSION = "2.0"
    
    # Mapping from obiTaxonomy.common_taxids() to taxids in STRING.
     
    TAXID_MAP = {"352472": "44689", # Dictyostelium discoideum
                 "562": None,
                 "2104": "272634", # Mycoplasma pneumoniae M129
                 "4530": "39947", # Oryza sativa Japonica Group
                 "4754": None,
                 "8355": None,
                 "4577": None
                 }
    
    
    def __init__(self):
        self.filename = orngServerFiles.localpath_download(self.DOMAIN, self.FILENAME)
        self.db = sqlite3.connect(self.filename)
        
    @classmethod
    def common_taxids(cls):
        common = obiTaxonomy.common_taxids()
        common = [cls.TAXID_MAP.get(id, id) for id in common]
        return filter(None, common)
    
    def organisms(self):
        """ Return all organism taxids contained in this database.
        """
        cur = self.db.execute("select distinct taxid from proteins")
        return [r[0] for r in cur.fetchall()]
    
    def ids(self, taxid=None):
        """ Return a list of all protein ids. If `taxid` is not None limit
        the results to ids from this organism only.
        
        """
        if taxid is not None:
            cur = self.db.execute("""\
                select protein_id
                from proteins
                where taxid=?
                """, (taxid,))
        else:
            cur = self.db.execute("""\
                select protein_id
                from proteins
                """)
        return [r[0] for r in cur.fetchall()]
    
    def synonyms(self, id):
        """ Return a list of synonyms for primary `id` as reported by STRING (proteins.aliases.{version}.txt file)
        """
        cur = self.db.execute("""\
            select alias
            from aliases
            where protein_id=?
            """, (id,))
        res = cur.fetchall()
        return [r[0] for r in res]
    
    def synonyms_with_source(self, id):
        """ Return a list of synonyms for primary `id` along 
        with its source as reported by STRING 
        (proteins.aliases.{version}.txt file)
        
        """
        cur = self.db.execute("""\
            select alias, source
            from aliases
            where protein_id=?
            """, (id,))
        res = cur.fetchall()
        return [(syn, set(source.split(" "))) \
                for syn, source in res]
    
    def all_edges(self, taxid=None):
        """ Return a list of all edges. If taxid is not None return the
        edges for this organism only.
        
        .. note:: This may take some time (and memory).
        
        """
        if taxid is not None:
            cur = self.db.execute("""\
                select links.protein_id1, links.protein_id2, score
                from links join proteins on
                    links.protein_id1=proteins.protein_id
                where taxid=?
                """, (taxid,))
        else:
            cur = self.db.execute("""\
                select protein_id1, protein_id1, score
                from links
                """)
        return cur.fetchall()
        
    def edges(self, id):
        """ Return a list of all edges (a list of 3-tuples (id1, id2, score)).
        """
        cur = self.db.execute("""\
            select protein_id1, protein_id2, score
            from links
            where protein_id1=?
            """, (id,))
        return cur.fetchall()
    
    def all_edges_annotated(self, taxid=None):
        """ Return a list of all edges annotated. If taxid is not None
        return the edges for this organism only.
        
        """
        res = []
        for id in self.ids(taxid):
            res.extend(self.edges_annotated(id))
        return res
        
    def edges_annotated(self, id):
        """ Return a list of all edges annotated.
        """
        cur = self.db.execute("""\
            select links.protein_id1, links.protein_id2, links.score, 
                   actions.action, actions.mode, actions.score
            from links left join actions on 
                   links.protein_id1=actions.protein_id1 and
                   links.protein_id2=actions.protein_id2
            where links.protein_id1=?
        """, (id,))
        return map(partial(apply,STRINGInteraction), cur.fetchall())
    
    def search_id(self, name, taxid=None):
        if taxid is None:
            cur = self.db.execute("""\
                select proteins.protein_id
                from proteins natural join aliases 
                where aliases.alias=?
            """, (name,))
        else:
            cur = self.db.execute("""\
                select proteins.protein_id
                from proteins natural join aliases 
                where aliases.alias=? and proteins.taxid=?
            """, (name, taxid))
        return map(itemgetter(0), cur)
        
    @classmethod
    def download_data(cls, version, taxids=None):
        """ Download the  PPI data for local work (this may take some time).
        Pass the version of the  STRING release e.g. v8.3.
        The resulting sqlite database will only contain the protein
        interactions for `taxids` (if None obiTaxonomy.common_taxids() will
        be used).
        
        """
        dir = orngServerFiles.localpath("PPI")

        base_url = "http://www.string-db.org/newstring_download/"
        links = base_url + "protein.links.{version}.txt.gz"
        actions = base_url + "protein.actions.{version}.txt.gz"
        aliases = base_url + "protein.aliases.{version}.txt.gz"
        
        wget(links.format(version=version), dir, progress=True)
        wget(actions.format(version=version), dir, progress=True)
        wget(aliases.format(version=version), dir, progress=True)
        
        links_filename = os.path.join(dir, "protein.links.{version}.txt".format(version=version))
        actions_filename = os.path.join(dir, "protein.actions.{version}.txt".format(version=version))
        aliases_filename = os.path.join(dir, "protein.aliases.{version}.txt".format(version=version))
        
        progress = ConsoleProgressBar("Extracting files:")
        progress(1.0)
        links_file = gzip.GzipFile(links_filename + ".gz", "rb")
        shutil.copyfileobj(links_file, open(links_filename, "wb"))
        
        progress(60.0)
        actions_file = gzip.GzipFile(actions_filename + ".gz", "rb")
        shutil.copyfileobj(actions_file, open(actions_filename, "wb"))
        
        progress(90.0)
        aliases_file = gzip.GzipFile(aliases_filename + ".gz", "rb")
        shutil.copyfileobj(aliases_file, open(aliases_filename, "wb"))
        progress.finish()
        
        cls.init_db(version, taxids)
        
    @classmethod
    def init_db(cls, version, taxids=None):
        """ Initialize the sqlite3 data base. `version` must contain a
        STRING release version e.g 'v8.3'. If `taxids` is not `None` it
        must contain a list of tax-ids in the STRING database for which
        to extract the interactions for.
        
        """
        def counter():
            i = 0
            while True:
                yield i
                i += 1
                
        protein_ids = defaultdict(counter().next)
        protein_taxid = {}

        dir = orngServerFiles.localpath(cls.DOMAIN)
        
        links_filename = os.path.join(dir, "protein.links.{version}.txt".format(version=version))
        actions_filename = os.path.join(dir, "protein.actions.{version}.txt".format(version=version))
        aliases_filename = os.path.join(dir, "protein.aliases.{version}.txt".format(version=version))
        
        links_file = open(links_filename, "rb")
        actions_file = open(actions_filename, "rb")
        aliases_file = open(aliases_filename, "rb")
        
        progress = ConsoleProgressBar("Processing links:")
        progress(0.0)
        filesize = os.stat(links_filename).st_size
        
        if taxids:
            taxids = set(taxids)
        else:
            taxids = set(cls.common_taxids())
                        
        con = sqlite3.connect(orngServerFiles.localpath(cls.DOMAIN, cls.FILENAME))
        
        with con:
            con.execute("drop table if exists links")
            con.execute("drop table if exists proteins")
            con.execute("drop table if exists actions")
            con.execute("drop table if exists aliases")
            
            con.execute("create table links (protein_id1 text, protein_id2 text, score int)")
            con.execute("create table proteins (protein_id text, taxid text)")
            con.execute("create table actions (protein_id1 text, protein_id2 text, mode text, action text, score int)")
            con.execute("create table aliases (protein_id text, alias text, source text)")
            
            header = links_file.readline() # read the header
            
            import csv
            reader = csv.reader(links_file, delimiter=" ")
            
            def read_links(reader, chunk_size=1000000):
                links = []
                i = 0
                split = str.split
                for p1, p2, score in reader:
                    if split(p1, ".", 1)[0] in taxids and split(p2, ".", 1)[0] in taxids:
                        links.append((intern(p1), intern(p2), int(score)))
                        if len(links) == chunk_size:
                            yield links
                            links = []
                    i += 1
                    if i % 1000 == 0: # Update the progress every 1000 lines
                        progress(100.0 * links_file.tell() / filesize)
                if links:
                    yield links
            
            for chunk in read_links(reader):
                con.executemany("insert into links values (?, ?, ?)", chunk)
            
            progress.finish()
            
            proteins = [res[0] for res in con.execute("select distinct protein_id1 from links")]
            progress = ConsoleProgressBar("Processing proteins:")
            
            def protein_taxids(proteins):
                protein_taxids = []
                for i, prot in enumerate(proteins):
                    taxid = prot.split(".", 1)[0]
                    protein_taxids.append((prot, taxid))
                    if i % 1000 == 0:
                        progress(100.0 * i / len(proteins))
                protein_taxids.sort()
                return protein_taxids
            
            con.executemany("insert into proteins values (?, ?)", protein_taxids(proteins))
            
            progress.finish()
            
            filesize = os.stat(actions_filename).st_size
            
            actions_file.readline() # read header
            
            progress = ConsoleProgressBar("Processing actions:")
            reader = csv.reader(actions_file, delimiter="\t")
            def read_actions(reader):
                actions = []
                i = 0
                split = str.split
                for p1, p2, mode, action, a_is_acting, score in reader:
                    if split(p1, ".", 1)[0] in taxids and split(p2, ".", 1)[0] in taxids:
                        actions.append((intern(p1), intern(p2), mode, action, int(score)))
                    i += 1
                    if i % 1000 == 0:
                        progress(100.0 * actions_file.tell() / filesize)
                actions.sort()
                return actions
            
            con.executemany("insert into actions values (?, ?, ?, ?, ?)", read_actions(reader))
            
            progress.finish()
            
            filesize = os.stat(aliases_filename).st_size
            aliases_file.readline() # read header
            
            progress = ConsoleProgressBar("Processing aliases:")
                            
            reader = csv.reader(aliases_file, delimiter="\t")
            def read_aliases(reader):
                i = 0
                for taxid, name, alias, source in reader:
                    if taxid in taxids:
                        yield (".".join([taxid, name]), 
                               alias.decode("utf-8", errors="ignore"), 
                               source.decode("utf-8", errors="ignore"),
                               )
                    i += 1
                    if i % 1000 == 0:
                        progress(100.0 * aliases_file.tell() / filesize)
                        
            con.executemany("insert into aliases values (?, ?, ?)", read_aliases(reader))
            
            progress.finish()

            print "Indexing the database"
            
            con.execute("""\
            create index if not exists index_link_protein_id1
                on links (protein_id1)""")
        
            con.execute("""\
                create index if not exists index_action_protein_id1
                    on actions (protein_id1)""")
            
            con.execute("""\
                create index if not exists index_proteins_id
                    on proteins (protein_id)""")
            
            con.execute("""\
                create index if not exists index_taxids
                    on proteins (taxid)""")
            
            con.execute("""\
                create index if not exists index_aliases_id
                    on aliases (protein_id)""")
            
            con.execute("""\
                create index if not exists index_aliases_alias
                    on aliases (alias)""")
            
            con.executescript("""
                DROP TABLE IF EXISTS version;
                
                CREATE TABLE version (
                     string_version text,
                     api_version text
                );""")
            
            con.execute("""
                INSERT INTO version
                VALUES (?, ?)""", (version, cls.VERSION))
            
        progress.finish()
        

STRINGDetailedInteraction = namedtuple("STRINGDetailedInteraction",
        ["protein_id1", "protein_id2", "combined_score", "mode",
         "action", "score", "neighborhood", "fusion", "cooccurence", 
         "coexpression", "experimental", "database", "textmining"
         ])

class STRINGDetailed(STRING):
    """  Access `STRING <http://www.string-db.org/>`_ PPI database.
    This class also allows access to subscores per channel.
    
    .. note:: This data is released under a 
        `Creative Commons Attribution-Noncommercial-Share Alike 3.0 License <http://creativecommons.org/licenses/by-nc-sa/3.0/>`_.
        If you want to use this data for commercial purpuses 
        you must get a license from STRING.
    
    """
    
    DATABASE_SCHEMA = """\
    DATABASE SCHEMA
    ===============
    
    table `evidence`:
        - `protein_id1`: protein id (text)
        - `protein_id2`: protein id (text)
        - `neighborhood`: score (int)
        - `fusion`: score (int)
        - `cooccurence`: score (int)
        - `coexpression`: score (int)
        - `experimental`: score (int)
        - `database`: score (int)
        - `textmining`: score (int)
        
    """
    FILENAME_DETAILED = "string-protein-detailed.sqlite"
    
    def __init__(self):
        STRING.__init__(self)
        db_file = orngServerFiles.localpath(self.DOMAIN, self.FILENAME)
        db_detailed_file = orngServerFiles.localpath_download(self.DOMAIN, self.FILENAME_DETAILED)
        self.db_detailed = sqlite3.connect(db_detailed_file)
        self.db_detailed.execute("ATTACH DATABASE ? as string", (db_file,))
        
    def edges_annotated(self, id):
        """ Return a list of all edges annotated.
        """
        edges = STRING.edges_annotated(self, id)
        edges_nc = []
        for edge in edges:
            id1, id2 = edge.protein_id1, edge.protein_id2
            cur = self.db_detailed.execute("""\
                SELECT neighborhood, fusion, cooccurence, coexpression,
                       experimental, database, textmining
                FROM evidence
                WHERE protein_id1=? AND protein_id2=?
                """, (id1, id2))
            res = cur.fetchone()
            if res:
                evidence = res
            else:
                evidence = [0] * 7
            edges_nc.append(
                STRINGDetailedInteraction(*(tuple(edge) + tuple(evidence)))
            )
        return edges_nc
        
    @classmethod
    def download_data(cls, version, taxids=None):
        import gzip, shutil, csv
        
        baseurl = "http://www.string-db.org/newstring_download/"
        links_filename = "protein.links.detailed.{version}.txt.gz".format(version=version)
        
        dir = orngServerFiles.localpath(cls.DOMAIN)
        local_filename = os.path.join(dir, links_filename)
         
        if not os.path.exists(local_filename):
            wget(baseurl + links_filename, dir, progress=True)
        else:
            print "Already downloaded - skiping"
            
        gz = gzip.open(os.path.join(dir, links_filename), "rb")

        # Strip .gz extension
        links_filename = os.path.join(dir, os.path.splitext(links_filename)[0])
        if not os.path.exists(links_filename):
            shutil.copyfileobj(gz, open(links_filename))
        
        cls.init_db(version, taxids)
            
    @classmethod
    def init_db(cls, version, taxids=None):
        import csv
        dir = orngServerFiles.localpath(cls.DOMAIN)
        
        links_filename = "protein.links.detailed.{version}.txt".format(version=version)
        links_filename = os.path.join(dir, links_filename)
        
        if taxids:
            taxids = set(taxids)
        else:
            taxids = set(cls.common_taxids())
        
        links_file = open(links_filename, "rb")
        
        con = sqlite3.connect(os.path.join(dir, cls.FILENAME_DETAILED))
        with con:
            con.execute("""\
                DROP TABLE IF EXISTS evidence
            """)
            
            con.execute("""\
                CREATE TABLE evidence(
                     protein_id1 TEXT,
                     protein_id2 TEXT,
                     neighborhood INTEGER, 
                     fusion INTEGER,
                     cooccurence INTEGER,
                     coexpression INTEGER,
                     experimental INTEGER,
                     database INTEGER,
                     textmining INTEGER
                    )
                """)
            
            links = csv.reader(links_file, delimiter=" ")
            links.next() # Read header
            filesize = os.stat(links_filename).st_size
            
            progress = ConsoleProgressBar("Processing links file:")
            progress(1.0)
            
            def read_links(reader, chunk_size=100000):
                split = str.split
                for links in chunks(reader, chunk_size):
                    chunk = []
                    for p1, p2, n, f, c, cx, ex, db, t, _ in links:
                        if split(p1, ".", 1)[0] in taxids and split(p2, ".", 1)[0] in taxids:
                            chunk.append((intern(p1), intern(p2), n, f, c, cx, ex, db, t))
                        
                    progress(100.0 * links_file.tell() / filesize)
                    if chunk:
                        yield chunk
            
            # The links are read in chunks for better performace 
            for chunk in read_links(links):
                con.executemany("""
                    INSERT INTO evidence 
                    VALUES  (?, ?, ?, ?, ?, ?, ?, ?, ?)
                    """, chunk)
        
            progress.finish()
            
            print "Indexing"
            con.execute("""\
                CREATE INDEX IF NOT EXISTS index_evidence
                    ON evidence (protein_id1, protein_id2)
            """)
            
            con.executescript("""
                DROP TABLE IF EXISTS version;
                
                CREATE TABLE version (
                     string_version text,
                     api_version text
                );
                """)
            
            con.execute("""
                INSERT INTO version
                VALUES (?, ?)""", (version, cls.VERSION))
        
        
class Interaction(object):
    def __init__(self, protein1, protein2, ref1=None, ref2=None, conf1=None, conf2=None):
        self.protein1, self.protein2 = protein1, protein2
        self.ref1, self.ref2 = ref1, ref2
        self.conf1, self.conf2 = conf1, conf2
        self.org1, self.org2 = None, None
    
class MIPS(object):
    VERSION = 1
    def __init__(self):
        self.load()
        
    def load(self):
        self.protein_names = defaultdict(set)
        self.refs = {}
        self.confidance = {}
        def process(element):
            d = {}
            participants = element.getElementsByTagName("proteinParticipant")
            proteins = []
            for protein in participants:
                interactor = protein.getElementsByTagName("proteinInteractor")[0]
                names = []
                for name in interactor.getElementsByTagName("shortLabel") + \
                            interactor.getElementsByTagName("fullName"):
                    names.append((name.tagName, name.childNodes[0].data))
                
                refs = []
                for ref in interactor.getElementsByTagName("primaryRef"):
                    refs += [(ref.tagName, ref.attributes.items())]
                org = dict(interactor.getElementsByTagName("organism")[0].attributes.items()).get("ncbiTaxId")
                conf = protein.getElementsByTagName("confidence")[0].attributes.items()
                proteins.append((names, refs, conf, org))
            interaction = Interaction(proteins[0][0][1][1], proteins[1][0][1][1])
            interaction.ref1, interaction.ref2 = proteins[0][1], proteins[1][1]
            interaction.conf1, interaction.conf2 = proteins[0][2], proteins[1][2]
            interaction.org1, interaction.org2 = proteins[0][3], proteins[1][3]
            
            self.protein_names[interaction.protein1].add(proteins[0][0][0][1])
            self.protein_names[interaction.protein2].add(proteins[1][0][0][1])
            
            return interaction 
            
        document = minidom.parse(orngServerFiles.localpath_download("PPI", "allppis.xml"))
        interactions = document.getElementsByTagName("interaction")
        self.interactions = [process(interaction) for interaction in interactions]
        
        self.protein_interactions = defaultdict(set)
        
        for inter in self.interactions:
            self.protein_names[inter.protein1] = dict(inter.ref1[0][1]).get("id")
            self.protein_names[inter.protein2] = dict(inter.ref2[0][1]).get("id")
            self.protein_interactions[inter.protein1].add(inter)
            self.protein_interactions[inter.protein2].add(inter) 
       
    def __iter__(self):
        return iter(self.interactions)
    
    @classmethod
    def download(cls):
        import urllib2, shutil
        src = urllib2.urlopen("http://mips.helmholtz-muenchen.de/proj/ppi/data/mppi.gz")
        dest = orngServerFiles.localpath("PPI", "mppi.gz")
        shutil.copyfileobj(src, open(dest, "wb"))
       
    @classmethod 
    @pickled_cache(None, [("PPI", "allppis.xml")], version=1)
    def _get_instance(cls):
        return MIPS()
    
    @classmethod
    def get_instance(cls):
        if not hasattr(cls, "_instance"):
            cls._instance= cls._get_instance()
        return cls._instance
    
def mips_interactions(protein = None):
    mips = MIPS.get_instance()
    if protein is None:
        return list(mips)
    else:
        return mips.protein_interactions.get(protein)

def mips_proteins():
    return set(MIPS.get_instance().protein_names.keys())

class BioGRIDInteraction(object):
    """ An object representing a BioGRID interaction. Each member of this object
    represents a data from a single column of BIOGRID-ALL.tab file.
    Attributes:
        - *interactor_a*    - BioGRID identifier
        - *interactor_b*    - BioGRID identifier
        - *official_symbol_a*    - An official symbol for *interactor_a*
        - *official_symbol_b*    - An official symbol for *interactor_b*
        - *aliases_for_a*    - Aliases separated by '|'
        - *aliases_for_b*    - Aliases separated by '|'
        - *experimental_system*     - Experimental system (see BioGRID documentation on www.thebiogrid.org for a list of valid entrys)
        - *source*    - 
        - *organism_a_id*    - NCBI Taxonomy identifier for *interactor_a*'s organism
        - *organism_b_id*    - NCBI Taxonomy identifier for *interactor_b*'s organism
    """
    __slots__ = ["interactor_a", "interactor_b", "official_symbol_a","official_symbol_b", "aliases_for_a", "aliases_for_b", "experimental_system", "source", "pubmed_id", "organism_a_id", "organism_b_id"]
    def __init__(self, line):
        for attr, val in zip(self.__slots__, line.split("\t")):
            setattr(self, attr, val)

class _BioGRID_Old(object):
    """ A BioGRID database interface
    Example::
        >>> ## finding all interactions for Homo sapiens sapiens
        >>> grid = BioGRID(case_insensitive=True)
        >>> proteins = proteins = biogrid.proteins() ## All proteins
        >>> proteins = [p for p in proteins if any(["9606" in [int.organism_a_id, int.organism_b_id] for int in grid.get(p)])]
    """
    VERSION = 1
    def __init__(self, case_insensitive=True):
#        warnings.warn("obiPPi._BioGRID_Old class is deprecated. Use obiPPI.BioGRID")
        self.case_insensitive = case_insensitive
        self._case = (lambda name: name.lower()) if self.case_insensitive else (lambda name: name)
        self.load()
        
    def load(self):
        text = open(orngServerFiles.localpath_download("PPI", "BIOGRID-ALL.tab"), "rb").read()
        text = text.split("SOURCE\tPUBMED_ID\tORGANISM_A_ID\tORGANISM_B_ID\n", 1)[-1]
        self.interactions = [BioGRIDInteraction(line) for line in text.splitlines() if line.strip()]
        
        self.protein_interactions = defaultdict(set)
        self.protein_names = {}
        
        case = self._case

        def update(keys, value, collection):
            for k in keys:
                collection.setdefault(k, set()).add(value)
                
        for inter in self.interactions:
            update(map(case, [inter.official_symbol_a] + inter.aliases_for_a.split("|")), case(inter.interactor_a), self.protein_names)
            update(map(case, [inter.official_symbol_b] + inter.aliases_for_b.split("|")), case(inter.interactor_b), self.protein_names)
            
            self.protein_interactions[case(inter.interactor_a)].add(inter)
            self.protein_interactions[case(inter.interactor_b)].add(inter)
            
        self.protein_interactions = dict(self.protein_interactions)

        if case("N/A") in self.protein_names:
            del self.protein_names[case("N/A")]
        
    def proteins(self):
        """ Return all protein names in BioGRID (from INTERACTOR_A, and INTERACTOR_B columns) 
        """
        return self.protein_interactions.keys()
            
    def __iter__(self):
        """ Iterate over all BioGRIDInteraction objects
        """
        return iter(self.interactions)
    
    def __getitem__(self, key):
        """ Return a list of protein interactions that a protein is a part of 
        """
        key = self._case(key)
#        keys = self.protein_alias_matcher.match(key)
        if key not in self.protein_interactions:
            keys = self.protein_names.get(key, [])
        else:
            keys = [key]
        if keys:
            return list(reduce(set.union, [self.protein_interactions.get(k, []) for k in keys], set()))
        else:
            raise KeyError(key)
    
    def get(self, key, default=None):
        """ Return a list of protein interactions that a protein is a part of
        """
        key = self._case(key)
#        keys = self.protein_alias_matcher.match(key)
        if key not in self.protein_interactions:
            keys = self.protein_names.get(keys, [])
        else:
            keys = [key] 
        if keys:
            return list(reduce(set.union, [self.protein_interactions.get(k, []) for k in keys], set()))
        else:
            return default
        
    @classmethod
    def get_instance(cls):
        if getattr(cls, "_instance", None) is None:
            cls._instance = _BioGRID_Old()
        return cls._instance
    
def biogrid_interactions(name=None):
    """Return a list of protein interactions (BioGRIDInteraction objects) that a protein is a part of
    """ 
    if name:
        return list(_BioGRID_Old.get_instance().get(name, set()))
    else:
        return _BioGRID_Old.get_instance().interactions
    
def biogrid_proteins():
    """ Return all protein names in BioGRID (from INTERACTOR_A, and INTERACTOR_B columns)
    """
    return _BioGRID_Old.get_instance().proteins()


if __name__ == "__main__":
    for protein in mips_proteins():
        print "Protein", protein, "interacts with", 
        print ",".join(set(reduce(list.__add__, [[inter.protein1, inter.protein2] for inter in mips_interactions(protein)], [])) -set([protein]))