Determination and validation of principal gene products.
BACKGROUND
Alternative splicing has the potential to generate a wide range of protein isoforms. For many computational applications and for experimental research, it is important to be able to concentrate on the isoform that retains the core biological function. For many genes this is far from clear.


RESULTS
We have combined five methods into a pipeline that allows us to detect the principal variant for a gene. Most of the methods were based on conservation between species, at the level of both gene and protein. The five methods used were the conservation of exonic structure, the detection of non-neutral evolution, the conservation of functional residues, the existence of a known protein structure and the abundance of vertebrate orthologues. The pipeline was able to determine a principal isoform for 83% of a set of well-annotated genes with multiple variants.
Tress
Michael L
ML
Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain. mtress@cnio.es
Wesselink
Jan-Jaap
JJ
Frankish
Adam
A
López
Gonzalo
G
Goldman
Nick
N
Löytynoja
Ari
A
Massingham
Tim
T
Pardi
Fabio
F
Whelan
Simon
S
Harrow
Jennifer
J
Valencia
Alfonso
A
D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling / Q000379:methods*; D020033:Protein Isoforms / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017421:Sequence Analysis / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
D020033:Protein Isoforms