Affiliations: National Center for Biotechnology Information,
National Library of Medicine, National Institutes of Health, Bethesda, Maryland
20894, USA, E-mail: [email protected] | National Center for Biotechnology Information,
National Library of Medicine, National Institutes of Health, Bethesda, Maryland
20894, USA, E-mail: [email protected]
Abstract: Functional annotation of proteins encoded in newly sequenced genomes
can be expected to meet two conflicting objectives: (i) provide as much
information as possible, and (ii) avoid erroneous functional assignments and
over-predictions. The continuing exponential growth of the number of sequenced
genomes makes the quality of sequence annotation a critical factor in the
efforts to utilize this new information. When dubious functional assignments
are used as a basis for subsequent predictions, they tend to proliferate,
leading to "database explosion". It is therefore important to identify the
common factors that hamper functional annotation. As a first step towards that
goal, we have compared the annotations of the Mycoplasma genitalium and
Methanococcus jannaschii genomes produced in several independent studies. The
most common causes of questionable predictions appear to be: i) non-critical
use of annotations from existing database entries; ii) taking into account only
the annotation of the best database hit; iii) insufficient masking of low
complexity regions (e.g. non-globular domains) in protein sequences, resulting
in spurious database hits obscuring relevant ones; iv) ignoring multi-domain
organization of the query proteins and/or the database hits; v) non-critical
functional inferences on the basis of the functions of neighboring genes in an
operon; vi) non-orthologous gene displacement, i.e. involvement of structurally
unrelated proteins in the same function. These observations suggest that case
by case validation of functional annotation by expert biologists remains
crucial for productive genome analysis.
