Title
In Silico screening for functional candidates amongst hypothetical proteins.
Abstract
The definition of a hypothetical protein is a protein that is predicted to be expressed from an open reading frame, but for which there is no experimental evidence of translation. Hypothetical proteins constitute a substantial fraction of proteomes of human as well as of other eukaryotes. With the general belief that the majority of hypothetical proteins are the product of pseudogenes, it is essential to have a tool with the ability of pinpointing the minority of hypothetical proteins with a high probability of being expressed.Here, we present an in silico selection strategy where eukaryotic hypothetical proteins are sorted according to two criteria that can be reliably identified in silico: the presence of subcellular targeting signals and presence of characterized protein domains. To validate the selection strategy we applied it on a database of human hypothetical proteins dating to 2006 and compared the proteins predicted to be expressed by our selecting strategy, with their status in 2008. For the comparison we focused on mitochondrial proteins, since considerable amounts of research have focused on this field in between 2006 and 2008. Therefore, many proteins, defined as hypothetical in 2006, have later been characterized as mitochondrial.Among the total amount of human proteins hypothetical in 2006, 21% have later been experimentally characterized and 6% of those have been shown to have a role in a mitochondrial context. In contrast, among the selected hypothetical proteins from the 2006 dataset, predicted by our strategy to have a mitochondrial role, 53-62% have later been experimentally characterized, and 85% of these have actually been assigned a role in mitochondria by 2008.Therefore our in silico selection strategy can be used to select the most promising candidates for subsequent in vitro and in vivo analyses.
Year
DOI
Venue
2009
10.1186/1471-2105-10-289
BMC Bioinformatics
Keywords
Field
DocType
microarrays,proteomics,algorithms,proteins,open reading frame,open reading frames,protein domains,computational biology,proteome,bioinformatics
Pseudogene,Protein domain,Biology,Proteomics,Open reading frame,Proteome,Bioinformatics,Computational biology,Genetics,Hypothetical protein,DNA microarray,In silico
Journal
Volume
Issue
ISSN
10
1
1471-2105
Citations 
PageRank 
References 
18
0.52
8
Authors
5
Name
Order
Citations
PageRank
Claus Desler1180.86
prashanth suravajhala2364.41
May Sanderhoff3180.52
Merete Rasmussen4180.52
Lene Juel Rasmussen5180.86