Bio::DB::Query::HIVQuery - Query interface to the Los Alamos HIV Sequence Database


BioPerl documentation Contained in the BioPerl distribution.

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NAME

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Bio::DB::Query::HIVQuery - Query interface to the Los Alamos HIV Sequence Database

SYNOPSIS

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    $q = new Bio::DB::Query::HIVQuery(" C[subtype] ZA[country] CXCR4[coreceptor] ");
    $q = new Bio::DB::Query::HIVQuery(
         -query=>{'subtype'=>'C', 
                  'country'=>'ZA', 
                  'coreceptor'=>'CXCR4'});

    $ac = $q->get_annotations_by_id(($q->ids)[0]);
    $ac->get_value('Geo', 'country')                    # returns 'SOUTH AFRICA'

    $db = new Bio::DB::HIV();
    $seqio = $db->get_Stream_by_query($q);              # returns annotated Bio::Seqs 

    # get subtype C sequences from South Africa and Brazil, 
    # with associated info on patient health, coreceptor use, and 
    # infection period:

    $q = new Bio::DB::Query::HIVQuery(
         -query => {
                    'query' => {'subtype'=>'C',
		    'country'=>['ZA', 'BR']},
                    'annot' => ['patient_health', 
                                'coreceptor', 
                                'days_post_infection']
                    });




DESCRIPTION

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Bio::DB::Query::HIVQuery provides a query-like interface to the cgi-based Los Alamos National Laboratory (LANL) HIV Sequence Database. It uses Bioperl facilities to capture both sequences and annotations in batch in an automated and computable way. Use with Bio::DB::HIV to create Bio::Seq objects and annotated Bio::SeqIO streams.

Query format

The interface implements a simple query language emulation that understands AND, OR, and parenthetical nesting. The basic query unit is

 (match1 match2 ...)[fieldname]

Sequences are returned for which fieldname equals match1 OR match2 OR .... These units can be combined with AND, OR and parentheses. For example:

 (B, C)[subtype] AND (2000, 2001, 2002, 2003)[year] AND ((CN)[country] OR (ZA)[country])

which can be shortened to

 (B C)[subtype] (2000 2001 2002 2003)[year] (CN ZA)[country]

The user can specify annotation fields, that do not restrict the query, but arrange for the return of the associated field data for each sequence returned. Specify annotation fields between curly braces, as in:

 (B C)[subtype] 2000[year] {country cd4_count cd8_count}

Annotations can be accessed off the query using methods described in APPENDIX.

Hash specifications for query construction

Single query specifications can be made as hash references provided to the -query argument of the constructor. There are two forms:

 -query => { 'country'=>'BR', 'phenotype'=>'NSI', 'cd4_count'=>'Any' }

equivalent to

 -query => [ 'country'=>'BR', 'phenotype'=>'NSI', 'cd4_count'=>'Any' ]

or

 -query => { 'query' => {'country'=>'BR', 'phenotype'=>'NSI'},
             'annot' => ['cd4_count'] }

In both cases, the CD4 count is included in the annotations returned, but does not restrict the rest of the query.

To 'OR' multiple values of a field, use an anonymous array ref:

 -query => { 'country'=>['ZA','BR','NL'], 'subtype'=>['A', 'C', 'D'] }

Valid query field names

An attempt was made to make the query field names natural and easy to remember. Aliases are specified in an XML file (lanl-schema.xml) that is part of the distribution. Custom field aliases can be set up by modifying this file.

An HTML cheatsheet with valid field names, aliases, and match data can be generated from the XML by using hiv_object->help('help.html'). A query can also be validated locally before it is unleashed on the server; see below.

Annotations

LANL DB annotations have been organized into a number of natural groupings, tagged Geo, Patient, Virus, and StdMap. After a successful query, each id is associated with a tree of Bio::Annotation::SimpleValue objects. These can be accessed with methods get_value and put_value described in APPENDIX.

Delayed/partial query runs

Accessing the LANL DB involves multiple HTTP requests. The query can be instructed to proceed through all (the default) or only some of them, using the named parameter RUN_OPTION.

To validate a query locally, use

 $q = new Bio::DB::Query::HIVQuery( -query => {...}, -RUN_OPTION=>0 )

which will throw an exception if a field name or option is invalid.

To get a query count only, you can save a server hit by using

 $q = new Bio::DB::Query::HIVQuery( -query => {...}, -RUN_OPTION=>1 )

and asking for $q->count. To finish the query, do

 $q->_do_query(2)

which picks up where you left off.

-RUN_OPTION=>2, the default, runs the full query, returning ids and annotations.

Query re-use

You can clear the query results, retaining the same LANL session and query spec, by doing $q->_reset. Change the query, and rerun with $q->_do_query($YOUR_RUN_OPTION).

FEEDBACK

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Mailing Lists

User feedback is an integral part of the evolution of this and other Bioperl modules. Send your comments and suggestions preferably to the Bioperl mailing list. Your participation is much appreciated.

  bioperl-l@bioperl.org                  - General discussion
  http://bioperl.org/wiki/Mailing_lists  - About the mailing lists

Support

Please direct usage questions or support issues to the mailing list:

bioperl-l@bioperl.org

rather than to the module maintainer directly. Many experienced and reponsive experts will be able look at the problem and quickly address it. Please include a thorough description of the problem with code and data examples if at all possible.

Reporting Bugs

Report bugs to the Bioperl bug tracking system to help us keep track of the bugs and their resolution. Bug reports can be submitted via the web:

  https://redmine.open-bio.org/projects/bioperl/

AUTHOR - Mark A. Jensen

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Email maj@fortinbras.us

CONTRIBUTORS

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Mark A. Jensen

APPENDIX

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The rest of the documentation details each of the object methods. Internal methods are usually preceded with a _

Constructor

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new

 Title   : new
 Usage   : my $hiv_query = new Bio::DB::Query::HIVQuery();
 Function: Builds a new Bio::DB::Query::HIVQuery object,
           running a sequence query against the Los Alamos
           HIV sequence database
 Returns : an instance of Bio::DB::Query::HIVQuery
 Args    :

QueryI compliance

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count

 Title   : count
 Usage   : $hiv_query->count($newval)
 Function: return number of sequences found
 Example : 
 Returns : value of count (a scalar)
 Args    : on set, new value (a scalar or undef, optional)
 Note    : count warns if it is accessed for reading before query
           has been executed to at least level 1

ids

 Title   : ids
 Usage   : $hiv_query->ids($newval)
 Function: LANL ids of returned sequences 
 Example : 
 Returns : value of ids (an arrayref of sequence accessions/ids)
 Args    : on set, new value (an arrayref or undef, optional)

query

 Title   : query
 Usage   : $hiv_query->query
 Function: Get/set the submitted query hash or string
 Example :
 Returns : hashref or string
 Args    : query in hash or string form (see DESCRIPTION)

Bio::DB::Query::HIVQuery specific methods

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help

 Title   : help
 Usage   : $hiv_query->help("help.html")
 Function: get html-formatted listing of valid fields/aliases/options
           based on current schema xml
 Example : perl -MBio::DB::Query::HIVQuery -e "new Bio::DB::Query::HIVQuery()->help" | lynx -stdin
 Returns : HTML
 Args    : optional filename; otherwise prints to stdout

Annotation manipulation methods

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get_annotations_by_ids

 Title   : get_annotations_by_ids (or ..._by_id)
 Usage   : $ac = $hiv_query->get_annotations_by_ids(@ids)
 Function: Get the Bio::Annotation::Collection for these sequence ids
 Example :
 Returns : A Bio::Annotation::Collection object
 Args    : an array of sequence ids

add_annotations_for_id

 Title   : add_annotations_for_id
 Usage   : $hiv_query->add_annotations_for_id( $id ) to create a new 
            empty collection for $id
           $hiv_query->add_annotations_for_id( $id, $ac ) to associate 
           $ac with $id
 Function: Associate a Bio::Annotation::Collection with this sequence id
 Example :
 Returns : a Bio::Annotation::Collection object
 Args    : sequence id [, Bio::Annotation::Collection object]

remove_annotations_for_ids

 Title   : remove_annotations_for_ids (or ..._for_id)
 Usage   : $hiv_query->remove_annotations_for_ids( @ids)
 Function: Remove annotation collection for this sequence id
 Example :
 Returns : An array of the previous annotation collections for these ids
 Args    : an array of sequence ids

remove_annotations

 Title   : remove_annotations
 Usage   : $hiv_query->remove_annotations()
 Function: Remove all annotation collections for this object
 Example :
 Returns : The previous annotation collection hash for this object
 Args    : none

get_value

 Title   : get_value
 Usage   : $ac->get_value($tagname) -or-
           $ac->get_value( $tag_level1, $tag_level2,... )
 Function: access the annotation value assocated with the given tags
 Example :
 Returns : a scalar
 Args    : an array of tagnames that descend into the annotation tree
 Note    : this is a L<Bio::AnnotationCollectionI> method added in 
           L<Bio::DB::HIV::HIVQueryHelper>

put_value

 Title   : put_value
 Usage   : $ac->put_value($tagname, $value) -or-
           $ac->put_value([$tag_level1, $tag_level2, ...], $value) -or-
           $ac->put_value( [$tag_level1, $tag_level2, ...] )
 Function: create a node in an annotation tree, and assign a scalar value to it
           if a value is specified
 Example :
 Returns : scalar or a Bio::AnnotationCollection object
 Args    : $tagname, $value scalars (can be specified as -KEYS=>$tagname,
           -VALUE=>$value) -or- 
           \@tagnames, $value (or as -KEYS=>\@tagnames, -VALUE=>$value )
 Notes   : This is a L<Bio::AnnotationCollectionI> method added in 
           L<Bio::DB::HIV::HIVQueryHelper>.
           If intervening nodes do not exist, put_value creates them, replacing 
           existing nodes. So if $ac->put_value('x', 10) was done, then later,
           $ac->put_value(['x', 'y'], 20), the original value of 'x' is trashed,
           and $ac->get_value('x') will now return the annotation collection 
           with tagname 'y'. 

get_keys

 Title   : get_keys
 Usage   : $ac->get_keys($tagname_level_1, $tagname_level_2,...)
 Function: Get an array of tagnames underneath the named tag nodes
 Example : # prints the values of the members of Category 1...
           print map { $ac->get_value($_) } $ac->get_keys('Category 1') ;
 Returns : array of tagnames or empty list if the arguments represent a leaf
 Args    : [array of] tagname[s]

GenBank accession manipulation methods

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get_accessions

 Title   : get_accessions
 Usage   : $hiv_query->get_accessions()
 Function: Return an array of GenBank accessions associated with these 
           sequences (available only after a query is subjected to a 
           full run (i.e., when $RUN_OPTION == 2)
 Example :
 Returns : array of gb accession numbers, or () if none found for this query
 Args    : none

get_accessions_by_ids

 Title   : get_accessions_by_ids (or ..._by_id)
 Usage   : $hiv_query->get_accessions_by_ids(@ids)
 Function: Return an array of GenBank accessions associated with these 
           LANL ids (available only after a query is subjected to a 
           full run (i.e., when $RUN_OPTION == 2)
 Example :
 Returns : array of gb accession numbers, or () if none found for this query
 Args    : none

Query control methods

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_do_query

 Title   : _do_query
 Usage   : $hiv_query->_do_query or $hiv_query->_do_query($run_level)
 Function: Execute the query according to argument or $RUN_OPTION
           and set _RUN_LEVEL
           extent of query reflects the value of argument
            0 : validate only (no HTTP action)
            1 : return sequence count only
            2 : return sequence ids (full query, returns with annotations)
           noop if current _RUN_LEVEL of query is >= argument or $RUN_OPTION,
 Example :
 Returns : actual _RUN_LEVEL (0, 1, or 2) achieved
 Args    : desired run level (optional, global $RUN_OPTION is default)

_reset

 Title   : _reset
 Usage   : $hiv_query->_reset
 Function: Resets query storage, count, and ids, while retaining session id, 
           original query string, and db schema
 Example : 
 Returns : void
 Args    : none

_session_id

 Title   : _session_id
 Usage   : $hiv_query->_session_id($newval)
 Function: Get/set HIV db session id (initialized in _do_lanl_request)
 Example : 
 Returns : value of _session_id (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

_run_level

 Title   : _run_level
 Usage   : $obj->_run_level($newval)
 Function: returns the level at which the query has so far been run
 Example : 
 Returns : value of _run_level (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

_run_option

 Title   : _run_option
 Usage   : $hiv_query->_run_option($newval)
 Function: Get/set HIV db query run option (see _do_query for values)
 Example : 
 Returns : value of _run_option (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

_ua_hash

 Title   : _ua_hash
 Usage   : $obj->_ua_hash($newval)
 Function: 
 Example : 
 Returns : value of _ua_hash (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

Internals

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add_id

 Title   : add_id
 Usage   : $hiv_query->add_id($id)
 Function: Add new id to ids
 Example : 
 Returns : the new id
 Args    : a sequence id

map_db

 Title   : map_db
 Usage   : $obj->map_db($newval)
 Function: 
 Example : 
 Returns : value of map_db (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

make_search_if

 Title   : make_search_if
 Usage   : $obj->make_search_if($newval)
 Function: 
 Example : 
 Returns : value of make_search_if (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

 Title   : search_
 Usage   : $obj->search_($newval)
 Function: 
 Example : 
 Returns : value of search_ (a scalar)
 Args    : on set, new value (a scalar or undef, optional)

_map_db_uri

 Title   : _map_db_uri
 Usage   :
 Function: return the full map_db uri ("Database Map")
 Example :
 Returns : scalar string
 Args    : none

_make_search_if_uri

 Title   : _make_search_if_uri
 Usage   :
 Function: return the full make_search_if uri ("Make Search Interface")
 Example :
 Returns : scalar string
 Args    : none

_search_uri

 Title   : _search_uri
 Usage   :
 Function: return the full search cgi uri ("Search Database")
 Example :
 Returns : scalar string
 Args    : none

_schema_file

 Title   : _schema_file
 Usage   : $hiv_query->_schema_file($newval)
 Function: 
 Example : 
 Returns : value of _schema_file (an XML string or filename)
 Args    : on set, new value (an XML string or filename, or undef, optional)

_schema

 Title   : _schema
 Usage   : $hiv_query->_schema($newVal)
 Function: 
 Example : 
 Returns : value of _schema (an HIVSchema object in package 
           L<Bio::DB::HIV::HIVQueryHelper>)
 Args    : none (field set directly in new())

_lanl_query

 Title   : _lanl_query
 Usage   : $hiv_query->_lanl_query(\@query_parms)
 Function: pushes \@query_parms onto @{$self->{'_lanl_query'}
 Example : 
 Returns : value of _lanl_query (an arrayref)
 Args    : on set, new value (an arrayref or undef, optional)

_lanl_response

 Title   : _lanl_response
 Usage   : $hiv_query->_lanl_response($response)
 Function: pushes $response onto @{$hiv_query->{'_lanl_response'}}
 Example : 
 Returns : value of _lanl_response (an arrayref of HTTP::Response objects)
 Args    : on set, new value (an HTTP::Response object or undef, optional)

_create_lanl_query

 Title   : _create_lanl_query
 Usage   : $hiv_query->_create_lanl_query()
 Function: validate query hash or string, prepare for _do_lanl_request
 Example : 
 Returns : 1 if successful; throws exception on invalid query
 Args    :

_do_lanl_request

 Title   : _do_lanl_request
 Usage   : $hiv_query->_do_lanl_request()
 Function: Perform search request on _create_lanl_query-validated query
 Example : 
 Returns : 1 if successful
 Args    : 

_parse_lanl_response

 Title   : _parse_lanl_response
 Usage   : $hiv_query->_parse_lanl_response()
 Function: Parse the tab-separated-value response obtained by _do_lanl_request
           for sequence ids, accessions, and annotations
 Example : 
 Returns : 1 if successful
 Args    : 

_parse_query_string

 Title   : _parse_query_string
 Usage   : $hiv_query->_parse_query_string($str)
 Function: Parses a query string using query language emulator QRY
         : in L<Bio::DB::Query::HIVQueryHelper>
 Example : 
 Returns : arrayref of hash structures suitable for passing to _create_lanl_query
 Args    : a string scalar

Dude, sorry-

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_sorry

 Title   : _sorry
 Usage   : $hiv_query->_sorry("-president=>Powell")
 Function: Throws an exception for unsupported option or parameter
 Example :
 Returns : 
 Args    : scalar string


BioPerl documentation Contained in the BioPerl distribution.
# to do: support for comment, reference annotations

# $Id: HIVQuery.pm 232 2008-12-11 14:51:51Z maj $
#
# BioPerl module for Bio::DB::Query::LANLQuery
#
# Please direct questions and support issues to <bioperl-l@bioperl.org> 
#
# Cared for by Mark A. Jensen <maj@fortinbras.us>
#
# Copyright Mark A. Jensen
#
# You may distribute this module under the same terms as perl itself

# POD documentation - main docs before the code

# Let the code begin...

package Bio::DB::Query::HIVQuery;
use strict;
use vars qw( $LANL_BASE $LANL_MAP_DB $LANL_MAKE_SEARCH_IF $LANL_SEARCH $SCHEMA_FILE $RUN_OPTION );

# Object preamble - inherits from Bio::DB::QueryI
use Bio::Root::Root;
use Bio::Annotation::Collection;
use Bio::Annotation::Comment;
use Bio::Annotation::Reference;
use Bio::WebAgent;
use XML::Simple;
use CGI;

use Bio::DB::HIV::HIVQueryHelper;

use base qw(Bio::Root::Root Bio::DB::QueryI);

# globals
BEGIN {
    # change base to new search page 01/14/09 /maj
    $LANL_BASE = "http://www.hiv.lanl.gov/components/sequence/HIV/asearch";
    $LANL_MAP_DB = "map_db.comp";
    $LANL_MAKE_SEARCH_IF = "make_search_if.comp";
    $LANL_SEARCH = "search.comp";
    $SCHEMA_FILE = Bio::Root::IO->catfile(qw(Bio DB HIV lanl-schema.xml));
    $RUN_OPTION = 2; # execute query
# exceptions
    @Bio::SchemaNotInit::Exception::ISA = qw( Bio::Root::Exception );
    @Bio::WebError::Exception::ISA = qw( Bio::Root::Exception );
    @Bio::QueryNotMade::Exception::ISA = qw( Bio::Root::Exception );
    @Bio::QueryStringException::Exception::ISA = qw( Bio::Root::Exception );
    @Bio::HIVSorry::Exception::ISA = qw ( Bio::Root::Exception );

}

sub new {
  my($class,@args) = @_;
  my $self = $class->SUPER::new(@args);
  # constructor option for web agent parameter spec: added 01/14/09 /maj
  my ($query, $ids, $lanl_base, $lanl_map_db, $lanl_make_search_if, $lanl_search, $schema_file,$run_option, $uahash) =
      $self->_rearrange([ qw(QUERY
                             IDS
                             LANL_BASE
                             LANL_MAP_DB
                             LANL_MAKE_SEARCH_IF
                             LANL_SEARCH
                             SCHEMA_FILE
                             RUN_OPTION
                             USER_AGENT_HASH
                            )], @args);

  # default globals
  $lanl_base||= $LANL_BASE;
  $lanl_map_db||=$LANL_MAP_DB;
  $lanl_make_search_if||=$LANL_MAKE_SEARCH_IF;
  $lanl_search||=$LANL_SEARCH;
  $schema_file||=$SCHEMA_FILE;
  $uahash ||= {timeout => 90};
  defined $run_option                || ($run_option = $RUN_OPTION);

  $self->lanl_base($lanl_base);
  $self->map_db($lanl_map_db);
  $self->make_search_if($lanl_make_search_if);
  $self->search_($lanl_search);
  $self->_run_option($run_option);
  $self->_ua_hash($uahash);
  
  # catch this at the top
  if (-e $schema_file) {
      $self->_schema_file($schema_file);
  }
  else { # look around
      my ($p) = $self->_schema_file( [grep {$_} map {
	  my $p = Bio::Root::IO->catfile($_, $schema_file);
	  $p if -e $p
				      } (@INC,"")]->[0]);
      $self->throw(-class=>"Bio::Root::NoSuchThing",
		   -text=>"Schema file \"".$self->_schema_file."\" cannot be found",
		   -value=>$self->_schema_file) unless -e $self->_schema_file;
  }

  $self->count(0);
  $self->{_schema} =  HIVSchema->new($self->_schema_file);

  # internal storage and flags
  $self->{'_lanl_query'} = [];
  $self->{'_lanl_response'} = []; 
  $self->{'_annotations'} = {}; # container for annotation collections assoc. with ids
  $self->{'_RUN_LEVEL'} = undef; # set in _do_query()
  
  # work
  defined $query               && $self->query($query);
  defined $ids                 && $self->ids($ids);
  
  # exec query

  $self->_do_query($self->_run_option) if $self->query;

  return $self;
}

sub count{
    my $self = shift;
    return $self->{'count'} = shift if @_;
    if (!$self->{'_RUN_LEVEL'} || ($self->{'_RUN_LEVEL'} < 1)) {
	$self->warn('Query not yet run at > level 1');
    }
    return $self->{'count'};
}

sub ids{
    my $self = shift;
    if (@_) {
	my $a = shift;
	$self->throw(-class=>'Bio::Root::BadParameter',
		     -text=>'Arrayref required',
		     -value=> ref $a) unless ref($a) eq 'ARRAY';
	if (@$a) {
	    @{$self->{'ids'}}{@$a} = (1) x @$a;
	    return $a;
	}
	else { #with empty arrayref, clear the hash
	    $self->{'ids'} = {};
	}
    }
    return keys %{$self->{'ids'}} if $self->{'ids'};
}

sub query {
    my $self = shift;
    return $self->{'query'} = shift if @_;
    return $self->{'query'};
}

sub help{
   my ($self, $fname) = @_;
   my (@ret, @tok);
   my $schema = $self->_schema;
   my $h = new CGI;

   my (@tbls, @flds, @als, @opts, $fh);
   if ($fname) {
       open ($fh, ">", $fname) or $self->throw(-class=>'Bio::Root::IOException',
                                               -text=>"Error opening help html file $fname for writing",
                                               -value=>$!);
   }
   else {
       open($fh, ">&1");
   }
   @tbls = $schema->tables;
   @tbls = ('COMMAND', grep !/COMMAND/,@tbls);
   print $fh (
       $h->start_html(-title=>"HIVQuery Help")
       );
   print $fh $h->a({-id=>'TOP'}, $h->h2("Valid <span style='font-variant:small-caps'>HIVQuery</span> query fields and match data"));
   print $fh "Fields are organized below according to their Los Alamos HIV database tables. Use aliases in place of full field names in queries; for example:<br/>";
   print $fh "<blockquote><code> (CCR5 CXCR4)[coreceptor]</code></blockquote>";
   print $fh "rather than";
   print $fh "<blockquote><code>(CCR5 CXCR4)[seq_sample.ssam_second_receptor] </code></blockquote>";
   print $fh "(which does work, however). Click hyperlinks to see valid search options within the field. The token <code><b>Any</b></code> is the wildcard for all fields.<br/><br/>";
   print $fh $h->start_table({-style=>"font-family:sans-serif;"}) ;
   foreach my $tbl (@tbls) {
       @flds = grep /^$tbl/, $schema->fields;
       @flds = grep !/_id/, @flds;
       print $fh (
	   $h->start_Tr({-style=>"background-color: lightblue;"}), 
	   $h->td([$h->a({-id=>$tbl},$tbl), $h->span({-style=>"font-style:italic"},"fields"), $h->span({-style=>"font-style:italic"}, "aliases")]),
	   $h->end_Tr
	   );
       foreach my $fld (@flds) {
	   @als = reverse $schema->aliases($fld);
	   print $fh (
	       $h->Tr( $h->td( ["", $h->a({-href=>"#opt$fld"}, shift @als), $h->code(join(',',@als))] ))
	       );
       my @tmp = grep {$_} $schema->options($fld);
	   @tmp = sort {(($a =~ /^[0-9]+$/) && $b =~ /^[0-9]+$/) ? $a<=>$b : $a cmp $b} @tmp;
	   if (grep /Any/,@tmp) {
	       @tmp = grep !/Any/, @tmp;
	       unshift @tmp, 'Any';
	   }
       #print STDERR join(', ',@tmp)."\n";
	   push @opts, $h->div(
	       {-style=>"font-family:sans-serif;font-size:small"},
	       $h->hr,
	       $h->a(
		   {-id=>"opt$fld"},
		   "<i>Valid options for</i> <b>$fld</b>: "),
	       $h->blockquote(
		   @tmp ? $h->code(join(", ", @tmp)) : $h->i("free text")
	       ),
	       $h->span(
		   "<i>Other aliases</i>: "),
	       $h->blockquote(
		   @als ? $h->code(join(",",@als)) : "<i>none</i>"
	       ),
	       " ", 
	       $h->table( $h->Tr( 
			      $h->td([
				  $h->a({-href=>"#$tbl"}, $h->small('BACK')), 
				  $h->a({-href=>"#TOP"}, $h->small('TOP'))
				     ]) ) )
	       );
	   
       }
   }
   print $fh $h->end_table;
   print $fh @opts;
   print $fh $h->end_html;
   close($fh);
   return 1;
}

sub get_annotations_by_ids{
    my $self = shift;
    my @ids = @_;
    my @ret;
    if (!$self->{'_RUN_LEVEL'} || ($self->{'_RUN_LEVEL'} < 2)) {
	$self->warn('Requires query run at level 2');
	return ();
    }
    @ret = map {$self->{'_annotations'}->{$_}} @ids if exists($self->{'_annotations'});

    return (wantarray ? @ret : $ret[0]) if @ret;
    return {};
}

# singular alias
sub get_annotations_by_id {
    shift->get_annotations_by_ids(@_);
}

sub add_annotations_for_id{
    my $self = shift;
    my ($id, $ac) = @_;
    $id = "" unless defined $id; # avoid warnings
    $ac = new Bio::Annotation::Collection unless defined $ac;
    $self->throw(-class=>'Bio::Root::BadParameter'
		 -text=>'Bio::Annotation::Collection required at arg 2',
		 -value=>"") unless ref($ac) eq 'Bio::Annotation::Collection';
    
    $self->{'_annotations'}->{$id} = $ac unless exists($self->{'_annotations'}->{$id});
    return $ac;
}

sub remove_annotations_for_ids {
    my $self = shift;
    my @ids = @_;
    my @ac;
    foreach (@ids) {
	push @ac, delete $self->{'_annotations'}->{$_};
    }
    return @ac;
}

# singular alias
sub remove_annotations_for_id {
    shift->remove_annotations_for_ids(@_);
}

sub remove_annotations {
    my $self = shift;

    my $ach = $self->{'_annotations'};
    $self->{'_annotations'} = {};
    return $ach;
}

sub get_accessions{
    my $self = shift; 
    my @ret;
    if (!$self->{'_RUN_LEVEL'} || ($self->{'_RUN_LEVEL'} < 2)) {
	$self->warn('Requires query run at level 2');
	return ();
    }
    my @ac = $self->get_annotations_by_ids($self->ids);
    foreach (@ac) {
	push @ret, $_->get_value('Special','accession');
    };
    return @ret;
}

sub get_accessions_by_ids {
    my $self = shift; 
    my @ids = @_;
    my @ret;
    if (!$self->{'_RUN_LEVEL'} || ($self->{'_RUN_LEVEL'} < 2)) {
	$self->warn('Requires query run at level 2');
	return ();
    }
    my @ac = $self->get_annotations_by_ids(@ids);
    foreach (@ac) {
	push @ret, $_->get_value('Special', 'accession');
    };
    return wantarray ? @ret : $ret[0];
}

# singular alias
sub get_accessions_by_id {
    shift->get_accessions_by_ids(@_);
}

##########    

sub _do_query{
   my ($self,$rl) = @_;
   $rl = $RUN_OPTION unless defined $rl;
   $self->throw(-class=>"Bio::Root::BadParameter",
		-text=>"Invalid run option \"$RUN_OPTION\"",
		-value=>$RUN_OPTION) unless grep /^$RUN_OPTION$/, (0, 1, 2);
   (!defined($self->{'_RUN_LEVEL'})) && do {
       $self->_create_lanl_query();
       $self->{'_RUN_LEVEL'} = 0;
   };
   ($rl > 0) && (!defined($self->{'_RUN_LEVEL'}) || ($self->{'_RUN_LEVEL'} <= 0)) && do {
       $self->_do_lanl_request();
       $self->{'_RUN_LEVEL'} = 1;
   };
   ($rl > 1) && (!defined($self->{'_RUN_LEVEL'}) || ($self->{'_RUN_LEVEL'} <= 1)) && do {
       $self->_parse_lanl_response();
       $self->{'_RUN_LEVEL'} = 2;
   };
   return $self->{'_RUN_LEVEL'};
}

sub _reset{
    my $self = shift;
    $self->ids([]);
    $self->count(0);
    $self->{'_annotations'} = {};
    $self->{'_lanl_response'} = [];
    $self->{'_lanl_query'} = [];
    $self->{'_RUN_LEVEL'} = undef;
    return;
}

sub _session_id{
    my $self = shift;

    return $self->{'_session_id'} = shift if @_;
    return $self->{'_session_id'};
}
sub _run_level{
    my $self = shift;

    return $self->{'_RUN_LEVEL'} = shift if @_;
    return $self->{'_RUN_LEVEL'};
}

sub _run_option{
    my $self = shift;

    return $self->{'_run_option'} = shift if @_;
    return $self->{'_run_option'};
}

sub _ua_hash{
    my $self = shift;
    if (@_) {
	for (ref $_[0]) {
	    $_ eq 'HASH' && do {
		$self->{'_ua_hash'} = $_[0];
		last;
	    };
	    !$_ && do {
		$self->{'_ua_hash'} = {@_};
		last;
	    };
	    do {
		$self->throw("Type ".ref($_)." unsupported as arg in _ua_hash");
	    };
	    
	}
    }
    return %{$self->{'_ua_hash'}};
}


#######

sub add_id {
    my $self = shift;
    my $id = shift;
    $id = "" unless defined $id; # avoid warnings
    ${$self->{'ids'}}{$id}++;
    return $id;
}


sub lanl_base{
    my $self = shift;
    return $self->{'lanl_base'} = shift if @_;
    return $self->{'lanl_base'};
}

sub map_db{
    my $self = shift;
    return $self->{'map_db'} = shift if @_;
    return $self->{'map_db'};
}

sub make_search_if{
    my $self = shift;
    return $self->{'make_search_if'} = shift if @_;
    return $self->{'make_search_if'};
}

sub search_{
    my $self = shift;
    return $self->{'search_'} = shift if @_;
    return $self->{'search_'};
}

sub _map_db_uri{
    my $self = shift;
    return $self->lanl_base."/".$self->map_db;
}
  

sub _make_search_if_uri{
    my $self = shift;
    return $self->lanl_base."/".$self->make_search_if;
}

sub _search_uri{
    my $self = shift;
    return $self->lanl_base."/".$self->search_;
}

sub _schema_file {
    my $self = shift;

    return $self->{'_schema_file'} = shift if @_;
    return $self->{'_schema_file'};
}

sub _schema{
    my $self = shift;
    
    $self->{'_schema'} ?
	return $self->{'_schema'} :
	$self->throw(-class=>'Bio::SchemaNotInit::Exception', 
		     -text=>"DB schema not initialized",
		     -value=>"");
	
}

sub _lanl_query{
    my $self = shift;
    my $a = shift;
    return $self->{'_lanl_query'} unless $a;
    if (ref $a eq 'ARRAY') {
	push @{$self->{'_lanl_query'}}, $a;
	return $a;
    }
    else {
	$self->throw(-class=>'Bio::Root::BadParameter',
		     -text=>'Array ref required for argument.',
		     -value=>$a);
    }

}

sub _lanl_response{
    my $self = shift;
    if (@_) {
	my $r = shift;
	$self->throw(-class=>'Bio::Root::BadParameter',
		     -text=>'Requires an HTTP::Response object',
		     -value=> ref $r) unless ref($r) eq 'HTTP::Response';
	push @{$self->{'_lanl_response'}}, $r;
	return $r;
    }
    return $self->{'_lanl_response'};
}

sub _create_lanl_query {
    my $self = shift;
    my (%inhash, @query, @qhashes);
    my ($schema, @validFields, @validAliases);
    
    for ($self->query) {
	!defined && do {
	    $self->throw(-class=>'Bio::Root::NoSuchThing',
			 -text=>'Query not specified',
			 -value=>'');
	    last;
	};
	ref eq 'HASH' && do {
	    %inhash = %$_;
	    if ( grep /HASH/, map {ref} values %inhash ) {
		# check for {query=>{},annot=>[]} style
		$self->throw(-class=>'Bio::Root::BadParameter',
			     -text=>'Query style unrecognized',
			     -value=>"") unless defined $inhash{query};
		push @qhashes, $_;
	    }
	    last;
	};
	ref eq 'ARRAY' && do {
	    $inhash{'query'} = {@$_};
	    push @qhashes, \%inhash;
	    last;
	};
	#else
	do {
	    @qhashes = $self->_parse_query_string($_);
	};
    }
    $schema = $self->_schema;
    @validFields = $schema->fields;
    @validAliases = $schema->aliases;

    # validate args based on the xml specification file
    # only checks blanks and fields with explicitly specified options
    # text fields can put anything, and the query will be run before 
    # an error is caught in these 
    foreach my $qh (@qhashes) {
	@query=();
	foreach my $k (keys %{$$qh{'query'}}) {
	    my $fld;
	    # validate field
	    if (grep /^$k$/, @validFields) {
		$fld = $k;
	    }
	    elsif (grep /^$k$/, @validAliases) {
		foreach (@validFields) {
		    if (grep (/^$k$/, $schema->aliases($_))) {
			$fld = $_;
			last;
		    }
		    # $fld contains the field corresp. to the alias
		}
	    }
	    else {
		$self->throw(-class=>'Bio::Root::BadParameter',
			     -text=>"Invalid field or alias \"$k\"",
			     -value=>$qh);
	    }
	    # validate matchdata
	    my $vf = $schema->_sfieldh($fld);
	    my @md = (ref($qh->{'query'}{$k}) eq 'ARRAY') ? @{$qh->{'query'}{$k}} : $qh->{'query'}{$k};
	    if ($$vf{type} eq 'text') {
		foreach (@md) {
		    $self->throw(-class=>'Bio::Root::BadParameter',
				 -text=>'Value for field \"$k\" cannot be empty',
				 -value=>$qh)
			if ($_ eq "") && ($$vf{blank_ok} eq 'false');
		}
	    }
	    elsif ($$vf{type} eq 'option') {
		foreach my $md (@md) {
		    $self->throw(-class=>'Bio::Root::BadParameter',
				 -text=>"Invalid value \"".$md."\" for field \"$fld\"",
				 -value=>$md)
			unless $$vf{option} && grep {defined $_ && /^$md$/} @{$$vf{option}};
		}
	    }
	    # validated; add to query
	    foreach (@md) {
		push @query, ($fld => $_);
	    }
	}
	if ($qh->{'annot'}) {
	    # validate the column names to be included in the query
	    # to obtain annotations
	    my @annot_cols = @{$qh->{'annot'}};
	    foreach my $k (@annot_cols) {
		my $fld;
		# validate field
		if (grep /^$k$/, @validFields) {
		    $fld = $k;
		}
		elsif (grep /^$k$/, @validAliases) {
		    foreach (@validFields) {
			if (grep (/^$k$/, $schema->aliases($_))) {
			    $fld = $_;
			    last;
			}
			# $fld should contain the field corresp. to the alias
		    }
		}
		else {
		    $self->throw(-class=>'Bio::Root::NoSuchThing',
				 -text=>"Invalid field or alias \"$k\"",
				 -value=>$k);
		}
		# lazy: 'Any' may not be the right default (but appears to 
		# be, based on the lanl html)
		push @query, ($fld => 'Any');
	    }
	}

	# insure that LANL and GenBank ids are retrieved
	push @query, ('sequenceentry.se_id' => 'Any') unless grep /SequenceEntry\.SE_id/, @query;
	push @query, ('sequenceaccessions.sa_genbankaccession' => 'Any')
	    unless grep /SequenceAccessions\.SA_GenBankAccession/, @query;

	# an "order" field is required by the LANL CGI
	# if not specified, default to SE_id

	push @query, ('order'=>'sequenceentry.se_id') unless grep /order/, @query;

	# @query now contains sfield=>matchdata pairs, as specified by user
	# include appropriate indexes to create correct automatic joins
	# established by the LANL CGI
	my (@qtbl, @qpk, @qfk);

	# the tables represented in query:
	my %q = @query; # squish the tables in the current query into hash keys
	@qtbl = $schema->tbl('-s', keys %q);

	if (@qtbl > 1) {
	    # more than one table, see if they can be connected
	    # get primary keys of query tables
	    @qpk = $schema->pk(@qtbl);

	    # we need to get each query table to join to 
	    # SequenceEntry.
	    #
	    # The schema is a graph with tables as nodes and 
	    # foreign keys<->primary keys as branches. To get a 
	    # join that works, need to include in the query
	    # all branches along a path from SequenceEntry 
	    # to each query table.
	    #
	    # find_join does it...
	    my @joink = map {
		my @k = $schema->find_join($_,'sequenceentry');
		map {$_ || ()} @k
	    } @qtbl;
	    # squish the keys in @joink 
	    my %j;
	    @j{@joink} = (1) x @joink;
	    @joink = keys %j;
	    # add the fields not currently in the query
	    foreach (@qpk, @joink) {
		my $fld = $_;
		if (!grep(/^$fld$/,keys %q)) {
		    # lazy: 'Any' may not be the right default (but appears to 
		    # be, based on the lanl html)
		    push @query, ($_ => 'Any');
		}
	    }

	}
	
	# set object property
	$self->_lanl_query([@query]);
    }
    return 1;
}

# _do_lanl_request : post the queries created by _create_lanl_query
# 
# @args (or {@args}) should be unaliased Table.Column=>Matchdata
# pairs (these will be used directly in the POSTs)

sub _do_lanl_request {
    my $self = shift;
    my (@queries, @query, @interface,$interfGet,$searchGet,$response);
    my ($numseqs, $count);

    # handle args
    if (!$self->_lanl_query) {
	$self->throw(-class=>"Bio::Root::BadParameter",
		     -text=>"_lanl_query empty, run _create_lanl_request first",
		     -value=>"");
    }
    else {
	@queries = @{$self->_lanl_query};
    }
    
    ## utility vars
    ## search site specific CGI parms
    my @search_pms = ('action'=>'Search');
    my @searchif_pms = ('action'=>'Search Interface');
    # don't get the actual sequence data here (i.e., the cgi parm 
    # 'incl_seq' remains undefined...
    my @download_pms = ('action Download.x'=>1, 'action Download.y'=>1);

    ## HTML-testing regexps
    my $tags_re = qr{(?:\s*<[^>]+>\s*)};
    my $session_id_re = qr{<input.*name="id".*value="([0-9a-f]+)"}m;
    my $search_form_re = qr{<form[^>]*action=".*/search.comp"};
    my $seqs_found_re = qr{Displaying$tags_re*(?:\s*[0-9-]*\s*)*$tags_re*of$tags_re*\s*([0-9]+)$tags_re*sequences found};
    my $no_seqs_found_re = qr{Sorry.*no sequences found};
    my $too_many_re = qr{too many records: $tags_re*([0-9]+)};
    my $sys_error_re = qr{[Ss]ystem error};
    my $sys_error_extract_re = qr{${tags_re}error:.*?<td[^>]+>${tags_re}(.*?)<br>};
    # find something like:
    #  <strong>tables without join:</strong><br>SequenceAccessions<br>
    my $tbl_no_join_re = qr{tables without join}i;
#    my $sorry_bud_re = qr{};


    foreach my $q (@queries) {
	@query = @$q;
	# default query control parameters
	my %qctrl = (
	    max_rec=>100,
	    sort_dir=>'ASC',
	    translate=>'FALSE' # nucleotides 
	    );
	
	# do work...

	# pull out commands, designated by the COMMAND pseudo-table...
	my @commands = map { $query[$_] =~ s/^COMMAND\.// ? @query[$_..$_+1] : () } (0..$#query-1);
	@query = map { $query[$_] =~ /^COMMAND/ ? () : @query[2*$_..2*$_+1] } (0..($#query-1)/2);

	
	# set control parameters explicitly made in query
	foreach my $cp (keys %qctrl) {
	    if (!grep( /^$cp$/, @query)) {
		push @query, ($cp, $qctrl{$cp});
	    }
	}

	# note that @interface must be an array, since a single 'key' (the table)
	# can be associated with multiple 'values' (the columns) in the POST 

	# squish fieldnames into hash keys
	my %q = @query;
	@interface = grep {defined} map {my ($tbl,$col) = /^(.*)\.(.*)$/} keys %q;
	my $err_val = ""; # to contain informative (ha!) value if error is parsed

	eval { # encapsulate communication errors here, defer biothrows...
        
        #mark the useragent should be setable from outside (so we can modify timeouts, etc)
	    my $ua = new Bio::WebAgent($self->_ua_hash);
	    my $idPing = $ua->get($self->_map_db_uri);
	    $idPing->is_success || do {
		$response=$idPing; 
		die "Connect failed";
	    };
	    # get the session id
	    if (!$self->_session_id) {
		($self->{'_session_id'}) = ($idPing->content =~ /$session_id_re/);
		$self->_session_id || do {
		    $response=$idPing; 
		    die "Session not established";
		};
	    }
	    # 10/07/08:
	    # strange bug: if action=>'Search+Interface' below (note "+"), 
	    # the response to the search (in $searchGet) shows the correct 
	    # >number< of sequences found, but also an error "No sequences 
	    # match" and an SQL barf. Changing the "+" to a " " sets up the 
	    # interface to lead to the actual sequences being delivered as 
	    # expected. maj
	    $interfGet = $ua->post($self->_make_search_if_uri, [@interface, @searchif_pms, id=>$self->_session_id]);
	    $interfGet->is_success || do {
		$response=$interfGet;
		die "Interface request failed";
	    };
	    # see if a search form was returned...
	    
	    $interfGet->content =~ /$search_form_re/ || do {
		$response=$interfGet; 
		die "Interface request failed";
	    };
	    
	    $searchGet = $ua->post($self->_search_uri, [@query, @commands, @search_pms, id=>$self->_session_id]);
	    $searchGet->is_success || do {
		$response = $searchGet;
		die "Search failed";
	    };
	    $response = $searchGet;
	    for ($searchGet->content) {
		/$no_seqs_found_re/ && do {
		    $err_val = 0;
		    die "No sequences found";
		    last;
		};
		/$too_many_re/ && do {
		    $err_val = $1;
		    die "Too many records ($1): must be <10000";
		    last;
		};
		/$tbl_no_join_re/ && do {
		    die "Some required tables went unjoined to query";
		    last;
		};
		/$sys_error_re/ && do {
		    /$sys_error_extract_re/;
		    $err_val = $1;
		    die "LANL system error";
		};
		/$seqs_found_re/ && do {
		    $numseqs = $1;
		    $count += $numseqs;
		    last;
		};
		# else...
		do {
		    die "Search failed (response not parsed)";
		};
	    }
	    $response = $ua->post($self->_search_uri, [@download_pms, id=>$self->_session_id]);
	    $response->is_success || die "Query failed";
	    # $response->content is a tab-separated value table of sequences 
	    # and metadata, first line starts with \# and contains fieldnames
	};
	$self->_lanl_response($response);
	# throw, if necessary
	if ($@) {
	    ($@ !~ "No sequences found") && do {
		$self->throw(-class=>'Bio::WebError::Exception',
			     -text=>$@,
			     -value=>$err_val);
	    };
	}
    }

    $self->warn("No sequences found for this query") unless $count;
    $self->count($count);
    return 1; # made it.

}

sub _parse_lanl_response {

### handle parsing and merging multiple responses into the query object
### (ids and annotations)
    my $self = shift;
    
    my ($seqGet) = (@_);
    my (@data, @cols, %antbl, %antype);
    my $numseq = 0;
    my ($schema, @retseqs, %rec, $ac);
    $schema = $self->_schema;
    
    $self->_lanl_response || 
	$self->throw(-class=>"Bio::QueryNotMade::Exception",
		     -text=>"Query not yet performed; call _do_lanl_request()",
		     -value=>"");
    foreach my $rsp (@{$self->_lanl_response}) {
	@data = split(/\r|\n/, $rsp->content);
	my $l;
	do {
	    $l = shift @data;
	} while ($l !~ /Number/);
	$numseq += ( $l =~ /Number.*:\s([0-9]+)/ )[0];
	@cols = split(/\t/, shift(@data));
	# mappings from column headings to annotation keys
	# squish into hash keys
	my %q = @{ shift @{$self->_lanl_query} };
	%antbl = $schema->ankh(keys %q);
	# get the category for each annotation
	map { $antype{ $_->{ankey} } = $_->{antype} } values %antbl;
	# normalize column headers
	map { tr/ /_/; $_ = lc; } @cols;
	foreach (@data) {
	    @rec{@cols} = split /\t/;
	    my $id = $rec{'se_id'};
	    $self->add_id($id);
	    $ac = new Bio::Annotation::Collection();
	    #create annotations
	    foreach (@cols) {
                next if $_ eq '#';
		my $t = $antype{$_} || "Unclassified";
		my $d = $rec{$_}; # the data
                $ac->put_value(-KEYS=>[$t, $_], -VALUE=>$d);
	    }
	    $self->add_annotations_for_id($id, $ac);	
	}
	1;
    }
    return 1; # made it.
}
    
sub _parse_query_string {
    my $self = shift;
    my $qstring = shift;
    my ($ptree, @ret);
    #syntax errors thrown in QRY (in HIVQueryHelper module)
    $ptree = QRY::_parse_q( $qstring );
    @ret = QRY::_make_q($ptree);
    return @ret;
}

sub _sorry{
    my $self = shift;
    my $parm = shift;
    $self->throw(-class=>"Bio::HIVSorry::Exception",
		 -text=>"Sorry, option/parameter \"$parm\" not (yet) supported. See manpage to complain.",
		 -value=>$parm);
    return;
}

1;