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Gene discovery by e-genetics: Drosophila odor and taste receptors

Junhyong Kim1,2 and John R. Carlson1,*

1 Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520-8103, USA
2 Department of Ecology and Evolutionary Biology and Department of Statistics, Yale University, P.O. Box 208106, New Haven, CT 06520-8106, USA



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  		Fig. 1. Construction of an n-dimensional protein space that allows interpolation. Each dimension represents a tested variable. Only three dimensions are shown. Tested variables included hydropathy, polarity, pI, pKa, molecular weight, and amino acid composition. Adapted from Warr et al. (Warr et al., 2001Go).

 


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  		Fig. 2. Refined parameters useful in distinguishing GPCRs from non-GPCRs. A sliding window recognizer is used to characterize the structure of a protein. A portion of an idealized GPCR is shown. Parameters selected as being particularly useful were (1) average periodicity of the hydrophobicity function; (2) average periodicity of the polarity function; (3) variance in the periodicity of the polarity function; (4) variance in the first derivative of the polarity function; and (5) amino acid usage index. Adapted from (Warr et al., 2001Go); parameters are described in more detail in Kim et al. (Kim et al., 2000Go).

 


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  		Fig. 3. Setting a discriminant function to maximally separate GPCRs from non-GPCRs in protein space. In a three-dimensional space, the function appears as a plane. The function was established using the training set of 750 known GPCRs and 1000 non-GPCRs. The function is used to classify novel proteins as either GPCRs or non-GPCRs, according to which side of the plane they map.

 


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  		Fig. 4. Testing the algorithm. The top panel shows that the algorithm correctly identified 96% of a test set of 100 known GPCRs and produced no false positives. The middle panel shows the performance of the algorithm on 100 amino-acid stretches of GPCRs and non-GPCRs. The bottom panel shows the performance of the algorithm, following retraining, with a set of GPCRs and ion channels.

 

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© The Company of Biologists Ltd 2002