From: brianf@dna.uvm.edu (Brain Foley)
Subject: Re: Re: Beyond GenBank.
Organization: Division of EMBA, University of Vermont
	<1992Dec16.091955.18559@husc3.harvard.edu>
Distribution: bionet.molbio.bio-matrix
Date: Wed, 16 Dec 1992 15:54:46 GMT

I have used ENTREZ a bit.  It does not really cover the type of things
I am talking about.  Yes, MEDLINE and GenBank and PIR and other
information storage-and-retrieval devices are much better than the old
methods of storing all information on paper.  But there is potential
for computerized information storage to evolve FAR beyond what we have
today.  

While one person might want each allele of the human ras oncogene
stored as a separate GenBank entry, with its own accession number,
(because it is after all another piece of DNA that was actually
sequenced and thus might tell us something about allelic variations,
error rates in sequencing or something else) other people would object
very strongly to a database that is full of such largely redundant
information and would want the data merged, with only SITES indicating
where the alleles differ.  For a relatively stable gene such as ras,
the merged entry seems reasonable, but when we get to MHC genes or
mature immunoglobulin genes the merged entries would be nightmares!
There are many other cases that fall in between.

GenBank has tried to be the database that pleases everyone and so it
pleases nobody completely.  If I am just doing a type of statistical
analysis such as codon usage bias in human, I do not want my curve
thrown off by all the redundant entries.  If I am looking for allelic
variation frequencies in humans, I want to see each sequence as a
separate entry so I don't have to spend three weeks writing code to
un-merge allelic sequences from a merged entry.

Only an expert on each gene can tell me if there are multiple copies
of this gene in the genome, and thus the two sequences may not be true
alleles, but only similar redundant genes.  I can imagine a gene that
gets duplicated, one evolves a promoter specific for increased
transcription during times of stress, the other keeps a steady
low-level of transcription at all times.  If only the cDNAs are
sequenced, differences might be attributed to allelic variation or
sequencing error in the FEATURES table, when in fact each diploid individual
carries two alleles of each gene.

The uses that people have for the database are so diverse that no one
version of GenBank can please everyone.  But people all over the world
are culling interesting sequences from GenBank (intron/exon splice
sites for example), fixing all the "bad" ones, doing interesting
analyses on them, and then publishing a paper-and-ink paper, such that
none of the rest of us can get our hands on that nice data set in
computer readable form.

Yes, that "intron/exon" database will soon be outdated if it is not 
maintained.  But it would be a good starting place for others to work
from.  Or pehaps all the "fixes" could get put back into Genbank?  But
one persons "fix" is another persons "mess"!

I feel that these issues do need to be discussed openly on the net, in
journals, and in public meetings.  We need to invite library
scientists, managers of information systems, database design
engineers, and all kinds of people to to help us work on solving some
of our problems.  Biologists are not the only people in the world that
have a lot of interesing data to manipulate.  And other fields are
currently working on solving problems that are very similar to our
own.

We also need to provide some funding and TRAINING/EDUCATION to get
more people involved PRODUCTIVELY in the process.  Complaining about
the way things are does not do as much good as working on a solution.

Sould everyone write down their "top ten list" of data sets that we
need to either incorporate into GenBank or store as separate
databases?  If we did this and mailed the lists to NCBI, what would
happen?  

--
********************************************************************
*  Brian Foley               *     If we knew what we were doing   *
*  Molecular Genetics Dept.  *     it wouldn't be called research  *
*  University of Vermont     *                                     *
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Newsgroups: bionet.molbio.bio-matrix