In Silico screening for functional candidates amongst hypothetical proteins

Claus Desler Madsen, Prashanth Suravajhala, May Sanderhoff, Merete Rasmussen, Lene Juel Rasmussen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstract

    Background: 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.

    Results: 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.

    Conclusion: 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.

    OriginalsprogEngelsk
    TidsskriftBMC Bioinformatics
    Vol/bind10
    Sider (fra-til)289
    ISSN1471-2105
    DOI
    StatusUdgivet - 2009

    Bibliografisk note

    Art. no. 1471

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