From: robison1@husc10.harvard.edu (Keith Robison)
Newsgroups: bionet.molbio.genbank
Subject: Re: Author errors and omissions.
Date: 14 Apr 92 13:02:41 GMT
Distribution: bionet

lamoran@gpu.utcs.utoronto.ca (L.A. Moran) writes:


>Keith Robison suggests several problems with sequence entries,

>Unfortunately it is not so easy for a computer to update old entries so the 
>task falls to someone who is knowledgeable and willing to spend enough time 
>to do the job correctly. 

	I disagree entirely.  It is all too EASY to update them
automatically -- you just have to unconvince yourself that it is difficult.
A particular example is over 200 entries which have each exon annotated
as a CDS, instead of a CDS  join(... -- I could write a program to fix
these in about a week, but since I can't directly fix GenBank I have
little incentive to.  If you can move data freely between flatfiles and
relationals, then it is easy to write programs to fix the data (since
you can do it all with tools you are familar with).
	I do not advocate a program which would make changes unguided,
only one which would find possible changes and make it as easy as
possible for a human curator to fix them (preferably <one keystroke/change).
The program could prepare a list of proposed corrections, the curator
would confirm them, and then tell the program to implement them.

	I really do know what I am talking about.  Since November, I have
reported many (>100) corrections to GenBank.  The vast majority of
these were detected automatically.  The entries in GenBank follow three
sets of rules -- the GenBank database format itself, the English language,
and the (still being defined) laws of biology.  If you can state a rule,
then you can write a program to test whether any entries break that
rule.  Most of the rule-breakers will be errors, and those which aren't
are likely to hold some interesting biology.



>I hope to go back and annotate the old HSP70 entries 
>and make a lot of corrections to more recent ones although it is still not 
>clear whether a third party (such as myself) has the right to alter other 
>people's entries. 

So long as the change is documented, ANYONE should be able to make 
corrections.  Add a REFERENCE L.A. Moran (Unpublished) field and
tack on /reference qualifiers to everything you add.


>There are several examples of old HSP70 sequences that are 
>known to be incorrect because the authors have published corrections that have
>not been entered in the database. In a couple of cases an entirely new, and 
>correct, entry has been created for an old incorrect sequence but the old 
>sequence remains in the database. Should it be deleted?

>Merges are a tricky problem. If two groups sequence the same gene should
>there be only one entry? What if the two sequences are not identical? If
>two sequences overlap should they be merged? Conversely, is anyone else
>bothered by the policy of having separate entries for each exon just because
>the entire intron was not sequenced? What should a curator do about these
>problems? We need to have a firm policy.

	These are both philosophical issues.  In my opinion, the solution
is to create "meta-entries", GenBank loci which contain no actual sequences
but instead instructions on merges and so forth using the same join syntax
used for multiple-entry CDSs, mRNAs, etc.  Other meta-entries could
list all known alleles of a given locus, all loci of a given family etc.
Extensive cross-referencing is also critical -- if one entry is replaced
by a corrected entry, then they should each reference each other
(replaces X0000; supersedes Y9999).
	This approach has several advantages.  First, you don't actually have
to execute merges -- no recalculating sequence coordinates for every entry
being merged (and every entry which references that entry).  Second, no
information is lost. Any discrepancies in the overlapping regions are
preserved for future biologists to ponder.

	In the end, the guiding principle should be "does this make
biological sense".  I seem to be the only person around who appreciates
that each exon is in a separate entry -- that makes the most biological
sense if ANY (but not ALL) of the intron was sequenced.  If good GenBank
parsers & processors were included with every sequence package, no
one would complain about these.
	Put another way, let us do things in a way which will make it easy
to do "grand merges" to generate entire genomes.


>Can anyone think of a way to encourage authors to look after their data?

	Social pressure and $$$. If it becomes socially unacceptable
to not annotate your sequences, then people will be likely to annotate
them. If granting agencies also leaned on people, it fully annotated
sequences would become common.


>Keith continues,

>        Too much time is spent by we end users doing the quality checks 
>        (and corrections) which should be performed by the keepers of the
>        databases."

>It is certainly true that you can't just retrieve the information from
>GenBank and trust it. You should retain a healthy degree of skepticism 
>concerning this data just as you would about most data which is published.
>This is particularly true when constructing evolutionary trees because
>the errors in some sequences will affect the topology.

	Of course you should retain a healthy degree of skepticism.
But preparing a dataset from GenBank should be something you do over
coffee, not weeks.  Wouldn't you be upset if 10% of the published 
phylogenetic trees were drawn incorrectly?


>I agree that SOME quality checks and corrections are the responsibility
>of the keepers of the databases and for the most part these checks are
>being performed currently. 

	Again, I disagree.  The only checks I know of are: 

		1) spelling checks on words in ORGANISM field
		2) translation check on CDS

(will those in the know please add what I have missed).


Even though they have been suggested frequently, automatic checks for
keyword spelling, vector sequence contamination, repetitive elements,
consensus site agreement, etc. are not performed routinely.  As a 
result, the community spends extra hours.  



>Laurence A. Moran (Larry)
>Dept. of Biochemistry               lamoran@gpu.utcs.utoronto.ca
>Medical Sciences Blgd.                    (416) 978-2704
>University of Toronto               FAX   (416) 978-8548
>Toronto M5S 1A8, CANADA



Keith Robison
Harvard University
Program in Biochemistry, Molecular, Cellular, and Developmental Biology

robison@ribo.harvard.edu 


P.S. Call me Keith or Robison -- using both sounds wierd!