There is a bioperl module that knows how to talk to NCBI's E-Utilities: see http://www.bioperl.org/wiki/HOWTO:EUtilities_Cookbook (it mentions homologene - I suppose it works, but I haven't tried it). You can also use the EUtilities directly. Both approaches have a slight learning curve.

Another, third approach is to download homologene into a local database. The NCBI E-Utilities work well, but working with homologene, I find it handier (and faster) to have all data locally, and use the file provided by NCBI in:

  ftp://ftp.ncbi.nih.gov/pub/HomoloGene/current/
[download]

 homologene_group_id | tax_id | geneid  |     symbol      | protein_gi
+ | protein_accession 
---------------------+--------+---------+-----------------+-----------
+-+-------------------
                   3 |   9606 |      34 | ACADM           |  187960098
+ | NP_001120800.1
                   3 |   9598 |  469356 | ACADM           |  114557331
+ | XP_524741.2
                   3 |   9615 |  490207 | ACADM           |   73960161
+ | XP_547328.2
                   3 |   9913 |  505968 | ACADM           |  115497690
+ | NP_001068703.1
                   3 |  10090 |   11364 | Acadm           |    6680618
+ | NP_031408.1
                   3 |  10116 |   24158 | Acadm           |    8392833
+ | NP_058682.1
                   3 |   7955 |  406283 | acadm           |   47085823
+ | NP_998254.1
                   3 |   7227 |   38864 | CG12262         |   24660351
+ | NP_648149.1
                   3 |   7165 | 1276346 | AgaP_AGAP005662 |   58387602
+ | XP_315683.2
                   3 |   6239 |  181757 | acdh-10         |   17569725
+ | NP_510788.1
(
[download]

What you want is to look up your human gene or accession (human: tax_id=9606), take the group_id, and see if there is a Drosophila melanogaster (fly: tax_id=7227) record within the same group id.

In case you have basic database skills, here is a way to load that file into a postgresql database:

#!/bin/sh

wget ftp://ftp.ncbi.nih.gov/pub/HomoloGene/current/homologene.data;

< homologene.data psql -c "
  drop table if exists my_homologene_data;
  create table         my_homologene_data (
    homologene_group_id  integer , 
    tax_id               integer , 
    geneid               integer , 
    symbol               text    , 
    protein_gi           integer , 
    protein_accession    text     
 );
 copy my_homologene_data from stdin csv delimiter E'\t';
";

echo "select count(*) from my_homologene_data" | psql;
[download]

The records that have the same group id are homologs.

select * from my_homologene_data where homologene_group_id = 31015
[download]

With that group id, you can easily construct links into specific NCBI homologene pages too:

http://www.ncbi.nlm.nih.gov/homologene/?term=31015
[download]

hth

P.S. Re zoological nomenclature: in the binomial name Drosophila melanogaster, 'melanogaster' is the epitheton and must *always* be lower case; only genus names must be capitalised.

I can't thank you enough for your help.

So I tried to do what you are saying by downloading the database. I got that far and I have the homologene.data file

 [zwc2101|login2] ~/TALL/ref/HomoloGene $ head homologene.data 
3    9606    34    ACADM    187960098    NP_001120800.1
3    9598    469356    ACADM    114557331    XP_524741.2
3    9615    490207    ACADM    73960161    XP_547328.2
3    9913    505968    ACADM    115497690    NP_001068703.1
3    10090    11364    Acadm    6680618    NP_031408.1
3    10116    24158    Acadm    8392833    NP_058682.1
3    7955    406283    acadm    47085823    NP_998254.1
3    7227    38864    CG12262    24660351    NP_648149.1
3    7165    1276346    AgaP_AGAP005662    58387602    XP_315683.2
3    6239    181757    acdh-10    17569725    NP_510788.1
[download]

I must say though that my "database" skills are not existent, I am good however at parsing and basic unix/perl/ matching etc... So from what you are saying ... the group id number will be the same for each gene (including its homologies should they be named differently) and that I just need to match the everything that has the group id for each human accession number, and then see if any of the lines match any of the Drosophila tax IDs? Thanks again for your help you have helped me tremendously!

Heres my code so far for this

 #!/usr/bin/perl -w
use strict;
open (FILEHANDLE,"$ARGV[0]") || die("Could not open OnlyNormal file");
   my @homo = <FILEHANDLE> ;
 close (FILEHANDLE);
   
 open (FILEHANDLE, "$ARGV[1]") || die("Could not open input file");
    my @file = <FILEHANDLE> ;
 close (FILEHANDLE);   
     foreach my $line (@homo)
     {
        chomp $line;
        (my $GroupID)=split(/\t/,$line);
        foreach my $Gene(@file)
        {
              chomp $Gene;
              if ($line =~m/\t$Gene\t/ && $line =~m/9606/) #Human Gene
+ name and Human Taxid
                    {
                     foreach my $LINE(@homo)
                        {
                           (my @drosophila)=split(/\t/,$LINE);
                           if ($LINE =~m/^$GroupID\t/ && $line =~m/722
+7/) # Gene group ID and Drosophila Tax ID
                               {
                                 print $Gene . "\t". $drosophila[3] . 
+"\n"; # [3] is the Drosophila Gene name at the group ID determined ab
+ove
                               }
                        
                        }
                    }
         }
     }
[download]

See also the NCBI explanatory files in:

ftp://ftp.ncbi.nih.gov/pub/HomoloGene
[download]

Especially the README file, which says:

----------------------------------------------------------
homologene.data is a tab delimited file containing the following
columns:

1) HID (HomoloGene group id)
2) Taxonomy ID
3) Gene ID
4) Gene Symbol
5) Protein gi
6) Protein accession
-----------------------------------------------------------
[download]

So yes, you search for your human accession in column 6, then look what value column 1 has (the homologene group id), and then look up whether there is a row which has both taxonomy_id=7227 (=D.melanogaster) *AND* that homologene group id.

Btw (if you want more data), the 'Gene ID' can be handy too as it gives you access to the whole of entrez, and lets you construct URL's into the main gene page, etc, etc. More data 'addressable' via 'gene id' in the files in:

ftp://ftp.ncbi.nih.gov/gene/DATA
[download]

(esp. gene_info and gene2accession)

(btw, I do /not/ see any Homologene records for your NP_001124398, so maybe your bioperl script does work after all, if you give it a human accession with known data in homologene)