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Reducing false-positive prediction of minimotifs with a genetic interaction filter.

Merlin JC, Rajasekaran S, Mi T, Schiller MR - PLoS ONE (2012)

Bottom Line: Any new approach that reduces false-positives will be of great help to biologists.We have built three filters that use genetic interactions to reduce false-positive minimotif predictions.Genetic interaction data sets can be used to reduce false-positive minimotif predictions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, United States of America.

ABSTRACT

Background: Minimotifs are short contiguous peptide sequences in proteins that have known functions. At its simplest level, the minimotif sequence is present in a source protein and has an activity relationship with a target, most of which are proteins. While many scientists routinely investigate new minimotif functions in proteins, the major web-based discovery tools have a high rate of false-positive prediction. Any new approach that reduces false-positives will be of great help to biologists.

Methods and findings: We have built three filters that use genetic interactions to reduce false-positive minimotif predictions. The basic filter identifies those minimotifs where the source/target protein pairs have a known genetic interaction. The HomoloGene genetic interaction filter extends these predictions to predicted genetic interactions of orthologous proteins and the node-based filter identifies those minimotifs where proteins that have a genetic interaction with the source or target have a genetic interaction. Each filter was evaluated with a test data set containing thousands of true and false-positives. Based on sensitivity and selectivity performance metrics, the basic filter had the best discrimination for true positives, whereas the node-based filter had the highest sensitivity. We have implemented these genetic interaction filters on the Minimotif Miner 2.3 website. The genetic interaction filter is particularly useful for improving predictions of posttranslational modifications such as phosphorylation and proteolytic cleavage sites.

Conclusions: Genetic interaction data sets can be used to reduce false-positive minimotif predictions. Minimotif prediction in known genetic interactions can help to refine the mechanisms behind the functional connection between genes revealed by genetic experimentation and screens.

Show MeSH
Screen Shot of Minimotif Miner 2.4 filter menu.GI filters were added as part of MnM website 2.4 located under the motif filter pull down section. The options for filtering with ‘GIs’ are outlined with a red box. This filter can be used on its own or in combination with filters. There are also options to check boxes to include or exclude minimotifs with GIs.
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pone-0032630-g002: Screen Shot of Minimotif Miner 2.4 filter menu.GI filters were added as part of MnM website 2.4 located under the motif filter pull down section. The options for filtering with ‘GIs’ are outlined with a red box. This filter can be used on its own or in combination with filters. There are also options to check boxes to include or exclude minimotifs with GIs.

Mentions: To enable the users to access these filters, we have updated the MnM 2.3 user interface to include these filters under the section of GI filters. This contains GI, GI-node and GI-HomoloGene filters (Figure 2). These filters can be applied to the resulting list of putative motifs by enabling the check box next to the respective filter. These filters can be used in combination with other filters. If it is preferred not to include the results based on a particular filter, there are options to disable the filter as well. Based on the filters selected, minimotif results table gets updated with the results that are retained by the filters. This enables the users to focus their search by allowing a better control on the selection criteria. The MnM help section has more information regarding filtering.


Reducing false-positive prediction of minimotifs with a genetic interaction filter.

Merlin JC, Rajasekaran S, Mi T, Schiller MR - PLoS ONE (2012)

Screen Shot of Minimotif Miner 2.4 filter menu.GI filters were added as part of MnM website 2.4 located under the motif filter pull down section. The options for filtering with ‘GIs’ are outlined with a red box. This filter can be used on its own or in combination with filters. There are also options to check boxes to include or exclude minimotifs with GIs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293834&req=5

pone-0032630-g002: Screen Shot of Minimotif Miner 2.4 filter menu.GI filters were added as part of MnM website 2.4 located under the motif filter pull down section. The options for filtering with ‘GIs’ are outlined with a red box. This filter can be used on its own or in combination with filters. There are also options to check boxes to include or exclude minimotifs with GIs.
Mentions: To enable the users to access these filters, we have updated the MnM 2.3 user interface to include these filters under the section of GI filters. This contains GI, GI-node and GI-HomoloGene filters (Figure 2). These filters can be applied to the resulting list of putative motifs by enabling the check box next to the respective filter. These filters can be used in combination with other filters. If it is preferred not to include the results based on a particular filter, there are options to disable the filter as well. Based on the filters selected, minimotif results table gets updated with the results that are retained by the filters. This enables the users to focus their search by allowing a better control on the selection criteria. The MnM help section has more information regarding filtering.

Bottom Line: Any new approach that reduces false-positives will be of great help to biologists.We have built three filters that use genetic interactions to reduce false-positive minimotif predictions.Genetic interaction data sets can be used to reduce false-positive minimotif predictions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, United States of America.

ABSTRACT

Background: Minimotifs are short contiguous peptide sequences in proteins that have known functions. At its simplest level, the minimotif sequence is present in a source protein and has an activity relationship with a target, most of which are proteins. While many scientists routinely investigate new minimotif functions in proteins, the major web-based discovery tools have a high rate of false-positive prediction. Any new approach that reduces false-positives will be of great help to biologists.

Methods and findings: We have built three filters that use genetic interactions to reduce false-positive minimotif predictions. The basic filter identifies those minimotifs where the source/target protein pairs have a known genetic interaction. The HomoloGene genetic interaction filter extends these predictions to predicted genetic interactions of orthologous proteins and the node-based filter identifies those minimotifs where proteins that have a genetic interaction with the source or target have a genetic interaction. Each filter was evaluated with a test data set containing thousands of true and false-positives. Based on sensitivity and selectivity performance metrics, the basic filter had the best discrimination for true positives, whereas the node-based filter had the highest sensitivity. We have implemented these genetic interaction filters on the Minimotif Miner 2.3 website. The genetic interaction filter is particularly useful for improving predictions of posttranslational modifications such as phosphorylation and proteolytic cleavage sites.

Conclusions: Genetic interaction data sets can be used to reduce false-positive minimotif predictions. Minimotif prediction in known genetic interactions can help to refine the mechanisms behind the functional connection between genes revealed by genetic experimentation and screens.

Show MeSH