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MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites.

Fukasawa Y, Tsuji J, Fu SC, Tomii K, Horton P, Imai K - Mol. Cell Proteomics (2015)

Bottom Line: Five-hundred and eighty of these genes were not annotated as mitochondrial in either UniProt or Gene Ontology.Interestingly, these include candidate regulators of parkin translocation to damaged mitochondria, and also many genes with known disease mutations, suggesting that careful investigation of MitoFates predictions may be helpful in elucidating the role of mitochondria in health and disease.MitoFates is open source with a convenient web server publicly available.

View Article: PubMed Central - PubMed

Affiliation: From the ‡Department of Computational Biology, Graduate School of Frontier Sciences, The University Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan;

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The three clusters of yeast presequences.A, Presequence feature vectors, colored by cluster, shown as mapped to three dimensions by PCA. B, Box plots of the nine features used for clustering are shown for each cluster.
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Figure 4: The three clusters of yeast presequences.A, Presequence feature vectors, colored by cluster, shown as mapped to three dimensions by PCA. B, Box plots of the nine features used for clustering are shown for each cluster.

Mentions: MitoFates improves the state-of-the-art in presequence prediction, but unfortunately still fails to predict a sizable number of presequences. Visual inspection of these false negatives reveals that they usually have fewer positively charged residues or poor score for MPP cleavage, suggesting they may belong to a different class of presequences than the true positives. To investigate this, we clustered 243 yeast presequences as described in Methods. The results suggests yeast presequences can be grouped into at least three clusters (supplemental Table S3), as visualized by primary component analysis (PCA) in Fig. 4A. The largest cluster (cluster I, blue in Fig. 4A) consists of 144 presequences that are strongly enriched for arginine and contain almost no negatively charged residues, exhibit typically low conservation (i.e. average value for presequences), a relatively well defined length distribution centered at an average of 25 residues, high PA score, and significantly higher MPP cleavage scores than other presequences. These properties are consistent with known features of presequences. However, the two remaining clusters differ in some ways from the classical view of presequences.


MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites.

Fukasawa Y, Tsuji J, Fu SC, Tomii K, Horton P, Imai K - Mol. Cell Proteomics (2015)

The three clusters of yeast presequences.A, Presequence feature vectors, colored by cluster, shown as mapped to three dimensions by PCA. B, Box plots of the nine features used for clustering are shown for each cluster.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390256&req=5

Figure 4: The three clusters of yeast presequences.A, Presequence feature vectors, colored by cluster, shown as mapped to three dimensions by PCA. B, Box plots of the nine features used for clustering are shown for each cluster.
Mentions: MitoFates improves the state-of-the-art in presequence prediction, but unfortunately still fails to predict a sizable number of presequences. Visual inspection of these false negatives reveals that they usually have fewer positively charged residues or poor score for MPP cleavage, suggesting they may belong to a different class of presequences than the true positives. To investigate this, we clustered 243 yeast presequences as described in Methods. The results suggests yeast presequences can be grouped into at least three clusters (supplemental Table S3), as visualized by primary component analysis (PCA) in Fig. 4A. The largest cluster (cluster I, blue in Fig. 4A) consists of 144 presequences that are strongly enriched for arginine and contain almost no negatively charged residues, exhibit typically low conservation (i.e. average value for presequences), a relatively well defined length distribution centered at an average of 25 residues, high PA score, and significantly higher MPP cleavage scores than other presequences. These properties are consistent with known features of presequences. However, the two remaining clusters differ in some ways from the classical view of presequences.

Bottom Line: Five-hundred and eighty of these genes were not annotated as mitochondrial in either UniProt or Gene Ontology.Interestingly, these include candidate regulators of parkin translocation to damaged mitochondria, and also many genes with known disease mutations, suggesting that careful investigation of MitoFates predictions may be helpful in elucidating the role of mitochondria in health and disease.MitoFates is open source with a convenient web server publicly available.

View Article: PubMed Central - PubMed

Affiliation: From the ‡Department of Computational Biology, Graduate School of Frontier Sciences, The University Tokyo, 5-1-5, Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan;

Show MeSH