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Efficacy of different protein descriptors in predicting protein functional families

BMC Bioinformatics volume 8, Article number: 300 (2007) Cite this article

Abstract

Background

Sequence-derived structural and physicochemical descriptors have frequently been used in machine learning prediction of protein functional families, thus there is a need to comparatively evaluate the effectiveness of these descriptor-sets by using the same method and parameter optimization algorithm, and to examine whether the combined use of these descriptor-sets help to improve predictive performance. Six individual descriptor-sets and four combination-sets were evaluated in support vector machines (SVM) prediction of six protein functional families.

Results

The performance of these descriptor-sets were ranked by Matthews correlation coefficient (MCC), and categorized into two groups based on their performance. While there is no overwhelmingly favourable choice of descriptor-sets, certain trends were found. The combination-sets tend to give slightly but consistently higher MCC values and thus overall best performance such that three out of four combination-sets show slightly better performance compared to one out of six individual descriptor-sets.

Conclusion

Our study suggests that currently used descriptor-sets are generally useful for classifying proteins and the prediction performance may be enhanced by exploring combinations of descriptors.

Background

Sequence-derived structural and physicochemical descriptors have frequently been used in machine learning prediction of protein structural and functional classes [1–5], protein-protein interactions [6–9], subcellular locations [10–16], peptides containing specific properties[17, 18], microarray data [19] and protein secondary structure prediction [20]. These descriptors serve to represent and distinguish proteins or peptides of different structural, functional and interaction profiles by exploring their distinguished features in compositions, correlations, and distributions of the constituent amino acids and their structural and physicochemical properties [2, 8, 21, 22]. There is thus a need to comparatively evaluate the effectiveness of these descriptor-sets for predicting different functional problems by using the same machine learning method and parameter optimization algorithm. Moreover, it is of interest to examine whether combined use of these descriptor-sets help to improve predictive performance.

This work is intended to evaluate the effectiveness of a total of six individual descriptor-sets and four combination-sets (Table 1) in the prediction of several protein functional families by using support vector machine (SVM). Six sets of individual descriptors and three combination-sets have been separately utilized in machine learning prediction of different protein functional and structural properties, all of which have shown impressive predictive performances [22–24]. The six individual sets are amino acid compositions [23] (Set D1), dipeptide compositions [24] (Set D2), normalized Moreau-Broto autocorrelation [25, 26] (Set D3), Moran autocorrelation [27] (Set D4), Geary autocorrelation [28] (Set D5), and the composition, transition and distribution of structural and physicochemical properties [2–6, 8, 17, 29, 30] (Set D6). The three combination-sets are quasi sequence order formed by weighted sums of amino acid compositions and physicochemical coupling correlations [10, 11, 18, 31] (Set D7), pseudo amino acid composition (PseAA) formed by weighted sums of amino acid compositions and physicochemical square correlations [23, 32] (Set D8), and combination of amino acid compositions and dipeptide compositions (Set D9) [24, 33]. In this work, we also considered a fourth combination-set that combines descriptor-sets D1 through D8 (Set D10).

Table 1 Protein descriptors commonly used for predicting protein functional families.
Full size table

The protein functional families studied here include enzyme EC2.4 [34–37], G protein-coupled receptors [38–40], transporter TC8.A [41], chlorophyll [42], lipid synthesis proteins involved in lipid synthesis [43], and rRNA-binding proteins. These six protein families were selected for testing the descriptor-sets based on their functional diversity, sample size and the range of reported family member prediction accuracies [2]. The reported prediction accuracies for these families are generally lower than those of other families [3], which are ideal for critically evaluating the effectiveness of these descriptor-sets; having a lower accuracy should enable a better differentiation of the performance of the various classes. SVM was used as the machine learning method for predicting these functional families because it is a popular method that has consistently been shown better performances than other machine learning methods [44, 45]. As this work is intended as a benchmarking study of the performance of various classes of descriptors, other than automatic optimization of results that is an integral part of the SVM programs, such as sigma value scanning, no further attempt was made to optimize the prediction performance of any descriptor class or of any dataset by manually tuning the parameters. Hence, prediction results reported in this paper might differ from those of reported studies.

EC2.4 includes glycosyltransferases that catalyze the synthesis of glycoconjugates and are involved in post-translational modification of proteins (glycosylation). Increased levels of glycosyltransferases have been found in disease states and inflammation [46, 47]. TC8.A consists of auxiliary transport proteins that facilitate transport across membranes, which play regulatory and structural roles [48]. GPCR represents G-protein coupled receptors that transduct signals for inducing cellular responses, and members of GPCR are of great pharmacological importance, as 50–60% of approved drugs elicit their therapeutic effect by selectively addressing members of the GPCR family [49–52]. Chlorophyll proteins are essential for harvesting solar energy in photosynthetic antenna systems [53]. Lipid synthesis proteins play central roles in such processes as metabolism, and deficiencies or altered functioning of lipid binding proteins are associated with disease states such as obesity, diabetes, atherosclerosis, hyperlipidemia and insulin resistance [54]. rRNA-binding proteins play central roles in the post-transcriptional regulation of gene expression [55, 56], and their binding capabilities are mediated by certain RNA binding domains and motifs [57–60].

Results and Discussion

The statistics of the six datasets are given in Table 2. Training and prediction statistics for each of the studied descriptor-sets are given in Table 3. Independent validation datasets were used to test the prediction accuracies. Among the 5-fold cross-validation test, independent dataset test and jackknife test, the jackknife is deemed the most rigorous [61]; however, it would have taken a lot of time to use SVM to conduct the jackknife test, thus as a compromise, here we adopted the independent dataset test. The program CDHIT [62–64] was used to remove redundancy at both 90% and 70% sequence identity so to avoid bias, subsequently, the datasets are tested again with the independent evaluation sets and the statistics are given in Table 4. It should be emphasized that the performance evaluation for the studied descriptor-sets are based only on the datasets studied in this work and the conclusions from this study might not be readily extended to other datasets.

Table 2 Summary of datasets statistics, including size of training, testing and independent evaluation sets, and average sequence length.
Full size table
Table 3 Dataset training statistics and prediction accuracies of six protein functional families. DS refers to descriptor set, where D1 = amino acid composition; D2 = dipeptide composition; D3 = Moreau-Broto autocorrelation; D4 = Moran autocorrelation; D5 = Geary autocorrelation; D6 = composition, transition and distribution descriptors; D7 = quasi sequence order; D8 = pseudo amino acid composition; D9 = combination of D1+D2; and D10 = combination of D1-D8. Predicted results given as TP (true positive), FN (false negative), TN (true negative), FP (false positive), Sen (sensitivity), Spec (specificity), Q (overall accuracy) and MCC (Matthews correlation coefficient).
Full size table
Table 4 Dataset statistics and prediction accuracies after homologous sequences removal (HSR) at 90% and 70% identity. DS refers to descriptor set, where D1 = amino acid composition; D2 = dipeptide composition; D3 = Moreau-Broto autocorrelation; D4 = Moran autocorrelation; D5 = Geary autocorrelation; D6 = composition, transition and distribution descriptors; D7 = quasi sequence order; D8 = pseudo amino acid composition; D9 = combination of D1+D2; and D10 = combination of D1-D8. Predicted results given as TP (true positive), FN (false negative), TN (true negative), FP (false positive), Sen (sensitivity), Spec (specificity), Q (overall accuracy) and MCC (Matthews correlation coefficient).
Full size table

The performance of the ten descriptor-sets were ranked by the Matthews correlation coefficient (MCC) values of the respective SVM prediction of the six functional families, which are given in Table 5. The computed MCC scores for these descriptor-sets are in the range of 0.64~0.97 for all protein families studied. Accordingly, the performance of these descriptor-sets is categorized into two groups based on their MCC values: 'Exceptional' (>0.85) and 'Good' (≤0.85). Moreover, these descriptor-sets are aligned in the order of their MCC values with "=" being of equal values and ">" indicating that one is better than the other. It is noted that, as the differences of many of these MCC values are rather small, such alignment is likely superficial to some extent and may not best reflect the real ranking of performance. Overall, the performances of these descriptor-sets are not significantly different, there is no overwhelmingly preferred descriptor-set, and SVM prediction performance appears to be highly dependent on the dataset.

Table 5 Descriptor sets ranked and grouped by MCC (Matthews correlation coefficient), before and after removal of homologous sequences at 90% and 70% identity, respectively.
Full size table

As shown in Table 3 and Table 4, for many of the studied datasets, the differences in prediction accuracies and MCC values between different descriptor-sets are small. In particular, for GPCR and rRNA binding proteins, the results of almost all descriptor-sets are in the 'Exceptional' category. Examining the range of MCC values of the descriptor-sets for each of the studied protein families (after removal of 70% homologous sequences), the differences between the largest and smallest MCC values are, in order of increasing magnitude: 0.10, 0.12, 0.14, 0.16, 0.21 and 0.21 for rRNA binding proteins, GPCR, TC8.A, lipid synthesis proteins, chlorophyll proteins and EC.2.4 families respectively. Given that a difference of 0.10 and 0.20 in MCC values translates to an approximate 4% and 7% difference in overall prediction accuracy, this separation is not large indeed.

Though the dataset is a more important determinant of prediction performance than the choice of descriptor class, a few general trends could be observed. Three out of four of the combination-sets tend to exhibit slightly but consistently higher MCC values for the protein families studied in this work. These sets are Sets D8, D9 and D10. In contrast, only one out of six individual sets, Set D6, tend to exhibit slightly but consistently higher MCC values for the protein families studied in this work. Therefore, statistically speaking, it appears that the use of combination-sets tend to give slightly better prediction performance than the use of individual-sets.

When each class was examined individually in this study, we find that the combination of amino acid composition and dipeptide composition (Set D9) tends to give consistently better results than that of the individual descriptor-sets (Set D1 and Set D2). It has been reported that one drawback of amino acid composition descriptors is that the same amino acid composition may correspond to diverse sequences as sequence order is lost [24, 33]. This sequence order information can be partially covered by considering dipeptide composition (Set D2). On the other hand, dipeptide composition lacks information concerning the fraction of the individual residue in the sequence, thus, a combination-set is expected to give better prediction results [24, 33, 65, 66].

Using all descriptor-sets (Set D10) generally, but not always, gives the best result, which is consistent with the findings on the use of molecular descriptors for predicting compounds of specific properties. [67, 68] For instance, Xue et al. found that feature selection methods are capable of reducing the noise generated by the use of overlapping and redundant molecular descriptors, and in some cases, improving the accuracy of SVM classification of pharmacokinetic behaviour of chemical agents [69]. In our study, for example, the three autocorrelation descriptor-sets (Sets D3, D4 and D5) all utilize the same physicochemical properties, only differing in the correlation algorithm. The use of all available descriptors likely results in the inclusion of partially redundant information, some of which may to some extent become noise that interferes with the prediction results or obscures relevant information. Based on the results of previous studies [69], it is possible that feature selection methods may be applied for selecting the optimal set of descriptors to improve prediction accuracy as well as computing efficiency for predicting protein functional families.

Conclusion

The effectiveness of ten protein descriptor-sets in six protein functional family prediction using SVM was evaluated. Corroborating with previous work done on chemical descriptors [67, 68, 70–76] and protein descriptors [4, 21, 30, 32, 35, 43, 77, 78], we found that the descriptor-sets evaluated in this paper, which comprise some of the commonly used descriptors, generally return good results and do not differ significantly. In particular, the use of combination descriptor-sets tends to give slightly better prediction performance than the use of individual descriptor-sets. While there seems to be no preferred descriptor-set that could be utilized for all datasets as prediction results is highly dependent on datasets, the performance of protein classification may be enhanced by selection of optimal combinations of descriptors using established feature-selection methods [79, 80]. Incorporation of appropriate sets of physicochemical properties not covered by some of the existing descriptor-sets may also help improving the prediction performance.

Methods

Datasets

The datasets were obtained from SwissProt [81], except for TC8.A, which was downloaded from Transport Classification Database (TCDB) [41]. These datasets were chosen for their functional diversity, sample size and the range of reported family member prediction accuracies. As SVM is essentially a statistical method, the datasets cannot be too small; yet it would also be convenient for the purposes of this study if they were not too large as to be unwieldy computationally. These downloaded datasets were used to construct the positive dataset for the corresponding SVM classification system. A negative dataset, representing non-class members, was generated by a well-established procedure [2, 3, 21, 30] such that all proteins was grouped into domain families [82] in the PFAM database, and the representative proteins of these families unrelated to the protein family being studied were chosen as negative samples.

These proteins, positive and negative, were further divided into separate training, testing and independent evaluation sets by the following procedure: First, proteins were converted into descriptor vectors and then clustered using hierarchical clustering into groups in the structural and physicochemical feature space [83], where more homologous sequences will have shorter distances between them, and the largest separation between clusters was set to a ceiling of 20. One representative protein was randomly selected from each group to form a training set that is sufficiently diverse and broadly distributed in the feature space. Another protein within the group was randomly selected to form the testing set. The selected proteins from each group were further checked to ensure that they are distinguished from the proteins in other groups. The remaining proteins were then designated as the independent evaluation set, also checked to be at a reasonable level of diversity. Fragments, defined as smaller than 60 residues, were discarded. This selection process ensures that the training, testing and evaluation sets constructed are sufficiently diverse and broadly distributed in the feature space. Though an analysis of the 'similar' proteins in each cluster showed that the majority of the proteins in a cluster are quite non-homologous, the program CDHIT (Cluster Database at High Identity with Tolerance) [62–64] was further used after the SVM model was trained to remove redundancy at both 90% and 70% sequence identity, so as to avoid bias as far as possible. CDHIT removes homologous sequences by clustering the protein dataset at some user-defined sequence identity threshold, for example 90%, and then generating a database of only the cluster representatives, thus eliminating sequences with greater than 90% identity. The statistical details are given in Tables 2 and 3.

Algorithms for generating protein descriptors

Ten sets of commonly used composition and physicochemical descriptors were generated from the protein sequence (see Table 1). These descriptors can be computed via the PROFEAT server [22].

Amino acid composition (Set D1) is defined as the fraction of each amino acid type in a sequence

f ( r ) = N r N , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGMbGzcqGGOaakcqWGYbGCcqGGPaqkcqGH9aqpdaWcaaqaaiabd6eaonaaBaaaleaacqWGYbGCaeqaaaGcbaGaemOta4eaaiabcYcaSaaa@3703@
(1)

where r = 1, 2, ..., 20, N r is the number of amino acid of type r, and N is the length of the sequence. Dipeptide composition (Set D2) is defined as

f r ( r , s ) = N r s N − 1 , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGMbGzcqWGYbGCcqGGOaakcqWGYbGCcqGGSaalcqWGZbWCcqGGPaqkcqGH9aqpdaWcaaqaaiabd6eaonaaBaaaleaacqWGYbGCcqWGZbWCaeqaaaGcbaGaemOta4KaeyOeI0IaeGymaedaaiabcYcaSaaa@3E0B@
(2)

where r, s = 1, 2, ..., 20, N ij is the number of dipeptides composed of amino acid types r and s.

Autocorrelation descriptors are a class of topological descriptors, also known as molecular connectivity indices, describe the level of correlation between two objects (protein or peptide sequences) in terms of their specific structural or physicochemical property [84], which are defined based on the distribution of amino acid properties along the sequence [85]. Eight amino acid properties are used for deriving the autocorrelation descriptors: hydrophobicity scale [86]; average flexibility index [87]; polarizability parameter [88]; free energy of amino acid solution in water [88]; residue accessible surface areas [89]; amino acid residue volumes [90]; steric parameters [91]; and relative mutability [92].

These autocorrelation properties are normalized and standardized such that

P r ' = P r − p ¯ σ , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGqbaudaqhaaWcbaGaemOCaihabaGaei4jaCcaaOGaeyypa0ZaaSaaaeaacqWGqbaudaWgaaWcbaGaemOCaihabeaakiabgkHiTiqbdchaWzaaraaabaacciGae83WdmhaaiabcYcaSaaa@3949@
(3)

where P ¯ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaaaa@2DED@ is the average value of a particular property of the 20 amino acids. P ¯ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaaaa@2DED@ and σ are given by

P ¯ = ∑ r = 1 20 P r 20 , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaiabg2da9maalaaabaWaaabCaeaacqWGqbaudaWgaaWcbaGaemOCaihabeaaaeaacqWGYbGCcqGH9aqpcqaIXaqmaeaacqaIYaGmcqaIWaama0GaeyyeIuoaaOqaaiabikdaYiabicdaWaaacqGGSaalaaa@3C09@
(4)

and

σ = 1 20 ∑ r = 1 20 ( P r − P ¯ ) 2 . MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaaiiGacqWFdpWCcqGH9aqpdaGcaaqaamaalaaabaGaeGymaedabaGaeGOmaiJaeGimaadaamaaqahabaGaeiikaGIaemiuaa1aaSbaaSqaaiabdkhaYbqabaGccqGHsislcuWGqbaugaqeaiabcMcaPmaaCaaaleqabaGaeGOmaidaaaqaaiabdkhaYjabg2da9iabigdaXaqaaiabikdaYiabicdaWaqdcqGHris5aaWcbeaakiabc6caUaaa@42AA@
(5)

Moreau-Broto autocorrelation descriptors (Set D3) [84, 93] are defined as

A C ( d ) = ∑ i = 1 N − d P i P i + d , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGbbqqcqWGdbWqcqGGOaakcqWGKbazcqGGPaqkcqGH9aqpdaaeWbqaaiabdcfaqnaaBaaaleaacqWGPbqAaeqaaOGaemiuaa1aaSbaaSqaaiabdMgaPjabgUcaRiabdsgaKbqabaaabaGaemyAaKMaeyypa0JaeGymaedabaGaemOta4KaeyOeI0IaemizaqganiabggHiLdGccqGGSaalaaa@4441@
(6)

where d = 1, 2, ..., 30 is the lag of the autocorrelation, and P i and Pi+dare the properties of the amino acid at positions i and i+d respectively. After applying normalization, we get

A T S ( d ) = A C ( d ) N − d . MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGbbqqcqWGubavcqWGtbWucqGGOaakcqWGKbazcqGGPaqkcqGH9aqpdaWcaaqaaiabdgeabjabdoeadjabcIcaOiabdsgaKjabcMcaPaqaaiabd6eaojabgkHiTiabdsgaKbaacqGGUaGlaaa@3D94@
(7)

Moran autocorrelation descriptors (Set D4) [94] are calculated as

I ( d ) = 1 N − d ∑ i = 1 N − d ( P i − P ¯ ) ( P i + d − P ¯ ) 1 N ∑ i = 1 N ( P i − P ¯ ) 2 , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=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@601F@
(8)

where d, P i and Pi+dare defined in the same way as that for Moreau-Broto autocorrelation and P ¯ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaaaa@2DED@ is the average of the considered property P along the sequence:

P ¯ = ∑ i = 1 N P i N . MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaiabg2da9maalaaabaWaaabCaeaacqWGqbaudaWgaaWcbaGaemyAaKgabeaaaeaacqWGPbqAcqGH9aqpcqaIXaqmaeaacqWGobGta0GaeyyeIuoaaOqaaiabd6eaobaacqGGUaGlaaa@3A73@
(9)

Geary autocorrelation descriptors (Set D5) [95] are written as

C ( d ) = 1 2 ( N − d ) ∑ i = 1 N − d ( P i − P i + d ) 2 1 N − 1 ∑ i = 1 N ( P i − P ¯ ) 2 , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGdbWqcqGGOaakcqWGKbazcqGGPaqkcqGH9aqpdaWcaaqaamaalaaabaGaeGymaedabaGaeGOmaiJaeiikaGIaemOta4KaeyOeI0IaemizaqMaeiykaKcaamaaqahabaGaeiikaGIaemiuaa1aaSbaaSqaaiabdMgaPbqabaGccqGHsislcqWGqbaudaWgaaWcbaGaemyAaKMaey4kaSIaemizaqgabeaakiabcMcaPmaaCaaaleqabaGaeGOmaidaaaqaaiabdMgaPjabg2da9iabigdaXaqaaiabd6eaojabgkHiTiabdsgaKbqdcqGHris5aaGcbaWaaSaaaeaacqaIXaqmaeaacqWGobGtcqGHsislcqaIXaqmaaWaaabCaeaacqGGOaakcqWGqbaudaWgaaWcbaGaemyAaKgabeaakiabgkHiTiqbdcfaqzaaraGaeiykaKYaaWbaaSqabeaacqaIYaGmaaaabaGaemyAaKMaeyypa0JaeGymaedabaGaemOta4eaniabggHiLdaaaOGaeiilaWcaaa@6087@
(10)

where d, P ¯ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuWGqbaugaqeaaaa@2DED@ , P i and Pi+dare defined as above. Comparing the three autocorrelation descriptors: while Moreau-Broto autocorrelation uses the property values as the basis for measurement, Moran autocorrelation utilizes property deviations from the average values, and Geary utilizes the square-difference of property values instead of vector-products (of property values or deviations). The Moran and Geary autocorrelation descriptors measure spatial autocorrelation, which is the correlation of a variable with itself through space.

The descriptors in Set D6 comprise of the composition (C), transition (T) and distribution (D) features of seven structural or physicochemical properties along a protein or peptide sequence [5, 29]. The seven physicochemical properties [2, 5, 29] are hydrophobicity; normalized Van der Waals volume; polarity; polarizibility; charge; secondary structures; and solvent accessibility. For each of these properties, the amino acids are divided into three groups such that those in a particular group are regarded to have approximately the same property. For instance, residues can be divided into hydrophobic (CVLIMFW), neutral (GASTPHY), and polar (RKEDQN) groups. C is defined as the number of residues with that particular property divided by the total number of residues in a protein sequence. T characterizes the percent frequency with which residues with a particular property is followed by residues of a different property. D measures the chain length within which the first, 25%, 50%, 75% and 100% of the amino acids with a particular property are located respectively. There are 21 elements representing these three descriptors: 3 for C, 3 for T and 15 for D, and the protein feature vector is constructed by sequentially combining the 21 elements for all of these properties and the 20 residues, resulting in a total of 188 dimensions.

The quasi-sequence order descriptors (Set D7) [96] are derived from both the Schneider-Wrede physicochemical distance matrix [10, 18, 97] and the Grantham chemical distance matrix [31], between each pair of the 20 amino acids. The physicochemical properties computed include hydrophobicity, hydrophilicity, polarity, and side-chain volume. Similar to the descriptors in Set D6, sequence order descriptors can also be used for representing amino acid distribution patterns of a specific physicochemical property along a protein or peptide sequence [18, 31]. For a protein chain of N amino acid residues R1R2...R N , the sequence order effect can be approximately reflected through a set of sequence order coupling numbers

τ d = ∑ i = 1 N − d ( d i , i + d ) 2 , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaaiiGacqWFepaDdaWgaaWcbaGaemizaqgabeaakiabg2da9maaqahabaGaeiikaGIaemizaq2aaSbaaSqaaiabdMgaPjabcYcaSiabdMgaPjabgUcaRiabdsgaKbqabaGccqGGPaqkdaahaaWcbeqaaiabikdaYaaaaeaacqWGPbqAcqGH9aqpcqaIXaqmaeaacqWGobGtcqGHsislcqWGKbaza0GaeyyeIuoakiabcYcaSaaa@44FB@
(11)

where τ d is the d th rank sequence order coupling number (d = 1, 2, ..., 30) that reflects the coupling mode between all of the most contiguous residues along a protein sequence, and di,i+dis the distance between the two amino acids at position i and i+d. For each amino acid type, the type 1 quasi sequence order descriptor can be defined as

X r = f r ∑ r = 1 20 f r + w ∑ d = 1 30 τ d , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGybawdaWgaaWcbaGaemOCaihabeaakiabg2da9maalaaabaGaemOzay2aaSbaaSqaaiabdkhaYbqabaaakeaadaaeWbqaaiabdAgaMnaaBaaaleaacqWGYbGCaeqaaOGaey4kaSIaem4DaC3aaabCaeaaiiGacqWFepaDdaWgaaWcbaGaemizaqgabeaaaeaacqWGKbazcqGH9aqpcqaIXaqmaeaacqaIZaWmcqaIWaama0GaeyyeIuoaaSqaaiabdkhaYjabg2da9iabigdaXaqaaiabikdaYiabicdaWaqdcqGHris5aaaakiabcYcaSaaa@4BFF@
(12)

where r = 1, 2, ..., 20, f r is the normalized occurrence of amino acid type i and w is a weighting factor (w = 0.1). The type 2 quasi sequence order is defined as

X d = w τ d − 20 ∑ r = 1 20 f r + w ∑ d = 1 30 τ d , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGybawdaWgaaWcbaGaemizaqgabeaakiabg2da9maalaaabaGaem4DaChcciGae8hXdq3aaSbaaSqaaiabdsgaKjabgkHiTiabikdaYiabicdaWaqabaaakeaadaaeWbqaaiabdAgaMnaaBaaaleaacqWGYbGCaeqaaOGaey4kaSIaem4DaC3aaabCaeaacqWFepaDdaWgaaWcbaGaemizaqgabeaaaeaacqWGKbazcqGH9aqpcqaIXaqmaeaacqaIZaWmcqaIWaama0GaeyyeIuoaaSqaaiabdkhaYjabg2da9iabigdaXaqaaiabikdaYiabicdaWaqdcqGHris5aaaakiabcYcaSaaa@5076@
(13)

where d = 21, 22, ..., 50. The combination of these two equations gives us a vector that describes a protein: the first 20 components reflect the effect of the amino acid composition, while the components from 21 to 50 reflect the effect of sequence order.

Similar to the quasi-sequence order descriptor, the pseudo amino acid descriptor (Set D8) is made up of a 50-dimensional vector in which the first 20 components reflect the effect of the amino acid composition and the remaining 30 components reflect the effect of sequence order, only now, the coupling number τ d is now replaced by the sequence order correlation factor θλ [32]. The set of sequence order correlated factors is defined as follows:

θ λ = 1 N − λ ∑ i = 1 L − λ Θ ( R i , R i + λ ) , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaaiiGacqWF4oqCdaWgaaWcbaGae83UdWgabeaakiabg2da9maalaaabaGaeGymaedabaGaemOta4KaeyOeI0Iae83UdWgaamaaqahabaGaeuiMdeLaeiikaGIaemOuai1aaSbaaSqaaiabdMgaPbqabaGccqGGSaalcqWGsbGudaWgaaWcbaGaemyAaKMaey4kaSIae83UdWgabeaakiabcMcaPaWcbaGaemyAaKMaeyypa0JaeGymaedabaGaemitaWKaeyOeI0Iae83UdWganiabggHiLdGccqGGSaalaaa@4C65@
(14)

where θλ is the first-tier correlation factor that reflects the sequence order correlation between all of the λ-most contiguous resides along a protein chain (λ = 1,...30) and N is the number of amino acid residues. Θ(R i , R j ) is the correlation factor and is given by

Θ ( R i , R j ) = 1 3 { [ H 1 ( R j ) − H 1 ( R i ) ] 2 + [ H 2 ( R j ) − H 2 ( R i ) ] 2 + [ M ( R j ) − M ( R i ) ] 2 } , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqqHyoqucqGGOaakcqWGsbGudaWgaaWcbaGaemyAaKgabeaakiabcYcaSiabdkfasnaaBaaaleaacqWGQbGAaeqaaOGaeiykaKIaeyypa0ZaaSaaaeaacqaIXaqmaeaacqaIZaWmaaWaaiWaaeaadaWadaqaaiabdIeainaaBaaaleaacqaIXaqmaeqaaOGaeiikaGIaemOuai1aaSbaaSqaaiabdQgaQbqabaGccqGGPaqkcqGHsislcqWGibasdaWgaaWcbaGaeGymaedabeaakiabcIcaOiabdkfasnaaBaaaleaacqWGPbqAaeqaaOGaeiykaKcacaGLBbGaayzxaaWaaWbaaSqabeaacqaIYaGmaaGccqGHRaWkdaWadaqaaiabdIeainaaBaaaleaacqaIYaGmaeqaaOGaeiikaGIaemOuai1aaSbaaSqaaiabdQgaQbqabaGccqGGPaqkcqGHsislcqWGibasdaWgaaWcbaGaeGOmaidabeaakiabcIcaOiabdkfasnaaBaaaleaacqWGPbqAaeqaaOGaeiykaKcacaGLBbGaayzxaaWaaWbaaSqabeaacqaIYaGmaaGccqGHRaWkdaWadaqaaiabd2eanjabcIcaOiabdkfasnaaBaaaleaacqWGQbGAaeqaaOGaeiykaKIaeyOeI0Iaemyta0KaeiikaGIaemOuai1aaSbaaSqaaiabdMgaPbqabaGccqGGPaqkaiaawUfacaGLDbaadaahaaWcbeqaaiabikdaYaaaaOGaay5Eaiaaw2haaiabcYcaSaaa@7006@
(15)

where H1(R i ), H2(R i ) and M(R i ) are the hydrophobicity [98], hydrophilicity [99] and side-chain mass of amino acid R i , respectively. Before being substituted in the above equation, the various physicochemical properties P(i) are subjected to a standard conversion,

P ( i ) = P 0 ( i ) − ∑ i = 1 20 P 0 ( i ) 20 ∑ i = 1 20 [ P 0 ( i ) − ∑ i = 1 20 P 0 ( i ) 20 ] 2 20 MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=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@68BB@
(16)

This sequence order correlation definition [Eqs. (14), (15)] introduce more correlation factors of physicochemical effects as compared to the coupling number [Eq. (11)], and has shown to be an improvement on the way sequence order effect information is represented [32, 35, 100]. Thus, for each amino acid type, the first part of the vector is defined as

X r = f r ∑ r = 1 20 f r + w ∑ d = 1 30 θ j , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGybawdaWgaaWcbaGaemOCaihabeaakiabg2da9maalaaabaGaemOzay2aaSbaaSqaaiabdkhaYbqabaaakeaadaaeWbqaaiabdAgaMnaaBaaaleaacqWGYbGCaeqaaOGaey4kaSIaem4DaC3aaabCaeaaiiGacqWF4oqCdaWgaaWcbaGaemOAaOgabeaaaeaacqWGKbazcqGH9aqpcqaIXaqmaeaacqaIZaWmcqaIWaama0GaeyyeIuoaaSqaaiabdkhaYjabg2da9iabigdaXaqaaiabikdaYiabicdaWaqdcqGHris5aaaakiabcYcaSaaa@4BFC@
(17)

where r = 1, 2, ..., 20, f r is the normalized occurrence of amino acid type i and w is a weighting factor (w = 0.1), and the second part is defined as

X d = w θ d − 20 ∑ r = 1 20 f r + w ∑ d = 1 30 ϑ λ . MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGybawdaWgaaWcbaGaemizaqgabeaakiabg2da9maalaaabaGaem4DaChcciGae8hUde3aaSbaaSqaaiabdsgaKjabgkHiTiabikdaYiabicdaWaqabaaakeaadaaeWbqaaiabdAgaMnaaBaaaleaacqWGYbGCaeqaaOGaey4kaSIaem4DaC3aaabCaeaacqWFrpGsdaWgaaWcbaGae83UdWgabeaaaeaacqWGKbazcqGH9aqpcqaIXaqmaeaacqaIZaWmcqaIWaama0GaeyyeIuoaaSqaaiabdkhaYjabg2da9iabigdaXaqaaiabikdaYiabicdaWaqdcqGHris5aaaakiabc6caUaaa@50AC@
(18)

Support Vector Machines (SVM)

As the SVM algorithms have been extensively described in the literature [2, 3, 101], only a brief description is given here. In the case of a linear SVM, a hyperplane that separates two different classes of feature vectors with a maximum margin is constructed. One class represents positive samples, for example EC2.4 proteins, and the other the negative samples. This hyperplane is constructed by finding a vector w and a parameter b that minimizes ||w||2 that satisfies the following conditions: w·x i + b ≥ 1, for y i = 1 (positive class) and w·x i + b ≤ -1, for y i = -1 (negative class). Here x i is a feature vector, y i is the group index, w is a vector normal to the hyperplane, | b | | | w | | MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaadaWcaaqaaiabcYha8jabdkgaIjabcYha8bqaaiabcYha8jabcYha8jabhEha3jabcYha8jabcYha8baaaaa@3884@ is the perpendicular distance from the hyperplane to the origin, and ||w||2 is the Euclidean norm of w. In the case of a nonlinear SVM, feature vectors are projected into a high dimensional feature space by using a kernel function such as K ( x i , x j ) = e − ‖ x i − x j ‖ 2 / 2 σ 2 MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGlbWscqGGOaakcqWH4baEdaWgaaWcbaGaemyAaKgabeaakiabcYcaSiabhIha4naaBaaaleaacqWGQbGAaeqaaOGaeiykaKIaeyypa0Jaemyzau2aaWbaaSqabeaacqGHsisldaqbdaqaaiabhIha4naaBaaameaacqWGPbqAaeqaaSGaeyOeI0IaeCiEaG3aaSbaaWqaaiabdQgaQbqabaaaliaawMa7caGLkWoadaahaaadbeqaaiabikdaYaaaliabc+caViabikdaYGGaciab=n8aZnaaCaaameqabaGaeGOmaidaaaaaaaa@4A11@ . The linear SVM procedure is then applied to the feature vectors in this feature space. After the determination of w and b, a given vector x can be classified by using sign [(w.x) + b], a positive or negative value indicating that the vector x belongs to the positive or negative class respectively.

As a discriminative method, the performance of SVM classification can be accessed by measuring the true positive TP (correctly predicted positive samples), false negative FN (positive samples incorrectly predicted as negative), true negative TN (correctly predicted negative samples), and false positive FP (negative samples incorrectly predicted as positive) [4, 102, 103]. As the numbers of positive and negative samples are imbalanced, the positive prediction accuracy or sensitivity Q p = TP/(TP+FN) and negative prediction accuracy or specificity Q n = TN/(TN+FP) [101] are also introduced. The overall accuracy is defined as Q = (TP+TN)/(TP+FN+TN+FP). However, in some cases, Q, Q p , and Q n are insufficient to provide a complete assessment of the performance of a discriminative method [102, 104]. Thus the Matthews correlation coefficient (MCC) was used in this work to evaluate the randomness of the prediction:

M C C = T P × T N − F P × F N ( T P + F N ) ( T P + F P ) ( T N + F P ) ( T N + F N ) , MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGnbqtcqWGdbWqcqWGdbWqcqGH9aqpdaWcaaqaaiabdsfaujabdcfaqjabgEna0kabdsfaujabd6eaojabgkHiTiabdAeagjabdcfaqjabgEna0kabdAeagjabd6eaobqaamaakaaabaGaeiikaGIaemivaqLaemiuaaLaey4kaSIaemOrayKaemOta4KaeiykaKIaeiikaGIaemivaqLaemiuaaLaey4kaSIaemOrayKaemiuaaLaeiykaKIaeiikaGIaemivaqLaemOta4Kaey4kaSIaemOrayKaemiuaaLaeiykaKIaeiikaGIaemivaqLaemOta4Kaey4kaSIaemOrayKaemOta4KaeiykaKcaleqaaaaakiabcYcaSaaa@5CEB@
(19)

where MCC ∈ [-1,1], with a negative value indicating disagreement of the prediction and a positive value indicating agreement. A zero value means the prediction is completely random. The MCC utilizes all four basic elements of the accuracy and it provides a better summary of the prediction performance than the overall accuracy.

References

  1. 1.

    Karchin R, Karplus K, Haussler D: Classifying G-protein coupled receptors with support vector machines. Bioinformatics 2002, 18: 147–159. 10.1093/bioinformatics/18.1.147

  2. 2.

    Cai CZ, Han LY, Ji ZL, Chen X, Chen YZ: SVM-Prot: web-based support vector machine software for functional classification of a protein from its primary sequence. Nuclei Acid Res 2003, 31: 3692–3697. 10.1093/nar/gkg600

  3. 3.

    Cai CZ, Han LY, Ji ZL, Chen YZ: Enzyme family classification by support vector machines. Proteins 2004, 55: 66–76. 10.1002/prot.20045

  4. 4.

    Han LY, Cai CZ, Lo SL, Chung MC, Chen YZ: Prediction of RNA-binding proteins from primary sequence by a support vector machine approach . RNA 2004, 10: 355–368. 10.1261/rna.5890304

  5. 5.

    Dubchak I, Muchnick I, Mayor C, Dralyuk I, Kim SH: Recognition of a protein fold in the context of the Structural Classification of Proteins (SCOP) classification. Proteins 1999, 35: 401–407. 10.1002/(SICI)1097-0134(19990601)35:4<401::AID-PROT3>3.0.CO;2-K

  6. 6.

    Bock JR, Gough DA: Predicting protein--protein interactions from primary structure. Bioinformatics 2001, 17: 455–460. 10.1093/bioinformatics/17.5.455

  7. 7.

    Bock JR, Gough DA: Whole-proteome interaction mining . Bioinformatics 2003, 19: 125–134. 10.1093/bioinformatics/19.1.125

  8. 8.

    Lo SL, Cai CZ, Chen YZ, Chung MC: Effect of training datasets on support vector machine prediction of protein-protein interactions. Proteomics 2005, 5: 876–884. 10.1002/pmic.200401118

  9. 9.

    Chou KC, Cai YD: Predicting protein-protein interactions from sequences in a hybridization space. J Proteome Res 2006, 5: 316–322. 10.1021/pr050331g

  10. 10.

    Chou KC: Prediction of protein subcellular locations by incorporating quasi-sequence-order effect. Biochem Biophys Res Commun 2000, 278: 477–483. 10.1006/bbrc.2000.3815

  11. 11.

    Chou KC, Cai YD: Prediction of protein subcellular locations by GO-FunD-PseAA predictor. Biochem Biophys Res Commun 2004, 320: 1236–1239. 10.1016/j.bbrc.2004.06.073

  12. 12.

    Chou KC, Shen HB: Hum-PLoc: A novel ensemble classifier for predicting human protein subcellular localization. Biochem Biophys Res Commun 2006, 347: 150–157. 10.1016/j.bbrc.2006.06.059

  13. 13.

    Chou KC, Shen HB: Large-scale plant protein subcellular location prediction. J Cell Biochem 2006, 100(3):665–678. 10.1002/jcb.21096

  14. 14.

    Bhasin M, Garg A, Raghava GP: PSLpred: prediction of subcellular localization of bacterial proteins. Bioinformatics 2005, 21(10):2522–2524. 10.1093/bioinformatics/bti309

  15. 15.

    Guo J, Lin Y, Liu XJ: GNBSL: a new integrative system to predict the subcellular location for Gram-negative bacteria proteins. Proteomics 2006, 6(19):5099–5105. 10.1002/pmic.200600064

  16. 16.

    Guo J, Lin Y: TSSub: eukaryotic protein subcellular localization by extracting features from profiles. Bioinformatics 2006, 22(14):1784–1785. 10.1093/bioinformatics/btl180

  17. 17.

    Cui J, Han LY, Lin HH, Zhang HL, Tang ZQ, Zheng CJ, Cao ZW, Chen YZ: Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties. Mol Immunol 2007, 44: 866–877. 10.1016/j.molimm.2006.04.001

  18. 18.

    Schneider G, Wrede P: The rational design of amino acid sequences by artificial neural networks and simulated molecular evolution: de novo design of an idealized leader peptidase cleavage site. Biophys J 1994, 66: 355–344.

  19. 19.

    Brown MP, Grundy WN, Lin D, Cristianini N, Sugnet CW, Furey TS, Ares MJ Jr, Haussler D: Knowledge-based analysis of microarray gene expression data by using support vector machines. Proc Natl Acad Sci USA 2000, 97(1):262–267. 10.1073/pnas.97.1.262

  20. 20.

    Ward JJ, McGuffin LJ, Buxton BF, Jones DT: Secondary structure prediction with support vector machines . Bioinformatics 2003, 19(13):1650–1655. 10.1093/bioinformatics/btg223

  21. 21.

    Han LY, Cai CZ, Ji ZL, Cao ZW, Cui J, Chen YZ: Predicting functional family of novel enzymes irrespective of sequence similarity: a statistical learning approach. Nuclei Acid Res 2004, 32: 6437–6444. 10.1093/nar/gkh984

  22. 22.

    Li ZR, Lin HH, Han LY, Jiang L, Chen X, Chen YZ: PROFEAT: A web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence. Nuclei Acid Res 2006, 34(Web Server issue):W32–37. 10.1093/nar/gkl305

  23. 23.

    Chou KC, Cai YD: Prediction of membrane protein types by incorporating amphipathic effects. J Chem Inf Model 2005, 45(2 ):407–413. 10.1021/ci049686v

  24. 24.

    Gao QB, Wang ZZ, Yan C, Du YH: Prediction of protein subcellular location using a combined feature of sequence. FEBS Lett 2005, 579(16):3444–3448. 10.1016/j.febslet.2005.05.021

  25. 25.

    Feng ZP, Zhang CT: Prediction of membrane protein types based on the hydrophobic index of amino acids. J Protein Chem 2000, 19: 262–275. 10.1023/A:1007091128394

  26. 26.

    Lin Z, Pan XM: Accurate prediction of protein secondary structural content. J Protein Chem 2001, 20: 217–220. 10.1023/A:1010967008838

  27. 27.

    Horne DS: Prediction of protein helix content from an autocorrelation analysis of sequence hydrophobicities. Biopolymers 1988, 27: 451–477. 10.1002/bip.360270308

  28. 28.

    Sokal RR, Thomson BA: Population structure inferred by local spatial autocorrelation: an example from an Amerindian tribal population. Am J Phys Anthropol 2006, 129: 121–131. 10.1002/ajpa.20250

  29. 29.

    Dubchak I, I M, Holbrook SR, Kim SH: Prediction of protein folding class using global description of amino acid sequence. Proc Natl Acad Sci USA 1995, 92: 8700–8704. 10.1073/pnas.92.19.8700

  30. 30.

    Lin HH, Han LY, Cai CZ, Ji ZL, Chen YZ: Prediction of transporter family from protein sequence by support vector machine approach. Proteins 2006, 62(1):218–231. 10.1002/prot.20605

  31. 31.

    Grantham R: Amino acid difference formula to help explain protein evolution. Science 1974, 185: 862–864. 10.1126/science.185.4154.862

  32. 32.

    Chou KC: Prediction of protein cellular attributes using pseudo amino acid composition. Proteins: Structure Function and Genetics 2001, 43: 246–255. 10.1002/prot.1035

  33. 33.

    Bhasin M, Raghava GP: Classification of nuclear receptors based on amino acid composition and dipeptide composition. J Biol Chem 2004, 279: 23262–23266. 10.1074/jbc.M401932200

  34. 34.

    NC-IUBMB: Enzyme Nomenclature. San Diego, California , Academic Press; 1992.

  35. 35.

    Chou KC: Using amphiphilic pseudo amino acid composition to predict enzyme subfamily classes. Bioinformatics 2005, 21: 10–19. 10.1093/bioinformatics/bth466

  36. 36.

    Chou KC, Cai YD: Predicting enzyme family class in a hybridization space. Protein Sci 2004, 13: 2857–2863. 10.1110/ps.04981104

  37. 37.

    Chou KC, Elrod DW: Prediction of enzyme family classes. J Proteome Res 2003, 2: 183–190. 10.1021/pr0255710

  38. 38.

    Chou KC: Prediction of G-protein-coupled receptor classes. J Proteome Res 2005, 4: 1413–1418. 10.1021/pr050087t

  39. 39.

    Chou KC, Elrod DW: Bioinformatical analysis of G-protein-coupled receptors. J Proteome Res 2002, 1: 429–433. 10.1021/pr025527k

  40. 40.

    Bhasin M, Raghava GP: GPCRpred: an SVM-based method for prediction of families and subfamilies of G-protein coupled receptors. Nuclei Acid Res 2004, 32(Web Server issue):W383–389. 10.1093/nar/gkh416

  41. 41.

    Saier MHJ, Tran CV, Barabote RD: TCDB: the Transporter Classification Database for membrane transport protein analyses and information. In Nuclei Acid Res. Volume 34. Saier Lab Bioinformatics Group; 2006:D181-D186. 10.1093/nar/gkj001

  42. 42.

    Suzuki JY, Bollivar DW, Bauer CE: Genetic analysis of chlorophyll biosynthesis. Annu Rev Genet 1997, 31: 61–89. 10.1146/annurev.genet.31.1.61

  43. 43.

    Lin HH, Han LY, Zhang HL, Zheng CJ, Xie B, Chen YZ: Prediction of the functional class of lipid binding proteins from sequence-derived properties irrespective of sequence similarity. J Lipid Res 2006, 47: 824–831. 10.1194/jlr.M500530-JLR200

  44. 44.

    Brown MP, Grundy WN, Lin D, Cristianini N, Sugnet CW, Furey TS, Ares MJ, Haussler D: Knowledge-based analysis of microarray gene expression data by using support vector machines. Proc Natl Acad Sci USA 2000, 97(1):262–267. 10.1073/pnas.97.1.262

  45. 45.

    Burbidge R, Trotter M, Buxton B, Holden S: Drug design by machine learning: support vector machines for pharmaceutical data analysis. Comput Chem 2001, 26(1):5–14. 10.1016/S0097-8485(01)00094-8

  46. 46.

    Baenzigner JU: Protein-specific glycosyltransferase: how and why they do it! FASEB J 1994, 8(13):1019–1025.

  47. 47.

    Kapitonov D, Yu RK: Conserved domains of glycosyltransferase. Glycobiology 1999, 9: 961–978. 10.1093/glycob/9.10.961

  48. 48.

    Busch W, Saier MHJ: The Transporter Classification (TC) system . Crit Rev Biochem Mol Biol 2002, 37(5):287–337. 10.1080/10409230290771528

  49. 49.

    Drews J: Genomic sciences and the medicine of tomorrow. Nat Biotechnol 1996, 14(11):1516–1518. 10.1038/nbt1196-1516

  50. 50.

    Gudermann TB, Nurnberg B, Schultz G: Receptors and G proteins as primary components of transmembrane signal transduction. Part 1. G-protein-coupled receptors: structure and function. J Mol Med 1995, 73(2):51–63. 10.1007/BF00270578

  51. 51.

    Muller G: Towards 3D structures of G protein-coupled receptors: a multidisciplinary approach. Curr Med Chem 2000, 7(9):861–888.

  52. 52.

    Paulson JC, Colley KJ: Glycosyltransferase. J Biol Chem 1989, 264(30):17645–17618.

  53. 53.

    Beale SI, Weinstein JD: Biochemistry and regulation of photosynthetic pigment formation in plants and algae. In Biosynthesis of Tetrapyrroles. Edited by: Jordan PM. Amsterdam , Elsevier; 1991:155–235.

  54. 54.

    Glatz JF, Luiken JJ, van Bilsen M, van der Vusse GJ: Cellular lipid binding proteins as facilitators and regulators of lipid metabolism. Mol Cell Biochem 2002, 239: 3–7. 10.1023/A:1020529918782

  55. 55.

    Burd CG, Dreyfuss G: Conserved structures and diversity of functions of RNA-binding proteins . Science 1994, 265: 615–621. 10.1126/science.8036511

  56. 56.

    Kiledjian M, Burd CG, Portman DS, Gorlach M, Dreyfuss G: Structure and function of hnRNP proteins. In RNA-Protein Interactions: Frontiers in Molecular Biology. Edited by: Nagai K, Mattaj IW. Oxford , IRL Press; 1994:127–149.

  57. 57.

    Draper DE: Themes in RNA-protein recognition. J Mol Biol 1999, 293: 255–270. 10.1006/jmbi.1999.2991

  58. 58.

    Fierro-Monti I, Mathews MB: Proteins binding to duplexed RNA: one motif, multiple functions. Trends Biochem Sci 2000, 25: 241–246. 10.1016/S0968-0004(00)01580-2

  59. 59.

    Perculis BA: RNA-binding proteins: If it looks like a sn(o)RNA. Curr Biol 2000, 10: R916-R918. 10.1016/S0960-9822(00)00851-4

  60. 60.

    Perez-Canadillas JM, Varani G: Recent advances in RNA-protein recognition. Curr Opin Struct Biol 2001, 11: 53–58. 10.1016/S0959-440X(00)00164-0

  61. 61.

    Chou KC, Zhang CT: Prediction of protein structural classes. Crit Rev Biochem Mol Biol 1995, 30(4):275–349.

  62. 62.

    Li WZ, Godzik A: Cd-hit: a fast program for clustering and comparing large sets of proteins or nucleotide sequences. Bioinformatics 2006, 22: 1658–1659. 10.1093/bioinformatics/btl158

  63. 63.

    Li WZ, Jaroszewksi L, Godzik A: Clustering of highly homologous sequences to reduce the size of large protein database. Bioinformatics 2001, 17: 282–283. 10.1093/bioinformatics/17.3.282

  64. 64.

    Li WZ, Jaroszewksi L, Godzik A: Tolerating some redundancy significantly speeds up clustering of large protein databases. Bioinformatics 2002, 18: 77–82. 10.1093/bioinformatics/18.1.77

  65. 65.

    Garg A, Bhasin M, Raghava GP: Support vector machine-based method for subcellular localization of human proteins using amino acid compositions, their order, and similarity search. J Biol Chem 2005, 280(15):14427014432. 10.1074/jbc.M411789200

  66. 66.

    Bhasin M, Raghava GP: ESLpred: SVM-based method for subcellular localization of eukaryotic proteins using dipeptide composition and PSI-BLAST. Nuclei Acid Res 2004, 32(Web Server issue):414–419. 10.1093/nar/gkh350

  67. 67.

    Xue L, Bajorath J: Molecular descriptors in chemoinformatics, computational combinatorial chemistry, and virtual screening. Comb Chem High Throughput Screen 2000, 3(5):363–372.

  68. 68.

    Xue L, Godden JW, Bajorath J: Identification of a preferred set of descriptors for compound classification based on principal component analysis. J Chem Inf Comput Sci 1999, 39: 669–704.

  69. 69.

    Xue Y, Li ZR, Yan CW, Sun LZ, Chen X, Chen YZ: Effect of molecular descriptor feature selection in support vector machine classification of pharmacokinetic and toxicological properties of chemical agents. J Chem Inf Comput Sci 2004, 44(5):1630–1638. 10.1021/ci049869h

  70. 70.

    Brown RD, Martin YC: Use of structure-activity data to compare structure-based clustering methods and descriptors for use in compound selection. J Chem Inf Comput Sci 1996, 36(3):572–584. 10.1021/ci9501047

  71. 71.

    Cramer RD, Patterson DE, Bunce JD: Comparative molecular field analysis (CoMFA): effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 1988, 110: 5959–5967. 10.1021/ja00226a005

  72. 72.

    Glen WG, Dunn WJ, Scott RD: Principal components analysis and partial least squares regression. Tetrahedron Comput Methodol 1989, 2: 349–376. 10.1016/0898-5529(89)90004-3

  73. 73.

    Matter H: Selecting optimally diverse compounds from structure databases: a validation study of two-dimensional and three-dimensional molecular descriptors. J Med Chem 1997, 40(8):1219–1229. 10.1021/jm960352+

  74. 74.

    Matter H, Pötter T: Comparing 3D pharmacophore triplets and 2D fingerprints for selecting diverse compound subsets. J Chem Inf Comput Sci 1999, 39: 1211–1225. 10.1021/ci980185h

  75. 75.

    Patterson DEP, Cramer RD, Ferguson AM, Clark RD, Weinberger LE: Neighborhood behavior: a useful concept for validation of "molecular diversity" descriptors. J Med Chem 1996, 39(16):049 -3059. 10.1021/jm960290n

  76. 76.

    Xue L, Godden JW, Bajorath J: Evaluation of descriptors and mini-fingerprints for the identification of molecules with similar activity. J Chem Inf Comput Sci 2000, 40(5):1227–1234. 10.1021/ci000327j

  77. 77.

    Lin HH, Han LY, Zhang HL, Zheng CJ, Xie B, Chen YZ: Prediction of the functional class of DNA-binding proteins from sequence derived structural and physicochemical properties. 2006.

  78. 78.

    Chen C, Zhou X, Tian Y, Zhou X, Cai P: Predicting protein structural class with pseudo-amino acid composition and support vector machine fusion network. Anal Biochem 2006, 357: 116–121. 10.1016/j.ab.2006.07.022

  79. 79.

    Furey TS, Cristianini N, Duffy N, Bednarski DW, Schummer M, Haussler D: Support vector machines classification and validation of cancer tissue samples using microarray expression data. Bioinformatics 2000, 16: 906–914. 10.1093/bioinformatics/16.10.906

  80. 80.

    Yu H, Yang J, Wang W, Han J: Discovering compact and highly discriminative features or feature combinations of drug activities using support vector machines. Proc IEEE Comput Soc Bioinform Conf 2003, (2):220–228.

  81. 81.

    Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O'Donovan C, Phan I, Pilbout S, Schneider M: The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nuclei Acid Res 2003, 31(1):365–370. 10.1093/nar/gkg095

  82. 82.

    Bateman A, Birney E, Cerruti L, Durbin R, Etwiller L, Eddy SR, Griffiths–Jones S, Howe KL, Marshall M, Sonnhammer EL: The Pfam protein families database. Nuclei Acid Res 2002, 31(1):276–280. 10.1093/nar/30.1.276

  83. 83.

    Heyer LJ, Kruglyak S, Yooseph S: Exploring expression data: Identification and analysis of coexpressed genes. Genome Res 1999, 9(11):1106–1115. 10.1101/gr.9.11.1106

  84. 84.

    Broto P, Moreau G, Vandicke C: Molecular structures: perception, autocorrelation descriptor and SAR studies. Eur J Med Chem 1984, 19: 71–78.

  85. 85.

    Kawashima S, Kanehisa M: AAindex: amino acid index database. Nuclei Acid Res 2000, 28: 374. 10.1093/nar/28.1.374

  86. 86.

    Cid H, Bunster M, Canales M, Gazitua F: Hydrophobicity and structural classes in proteins. Protein Eng 1992, 5: 373–375. 10.1093/protein/5.5.373

  87. 87.

    Bhaskaran R, Ponnuswammy PK: Positional flexibilities of amino acid residues in globular proteins. Int J Pept Protein Res 1988, 32: 242–255.

  88. 88.

    Charton M, Charton BI: The structural dependence of amino acid hydrophobicity parameters. J Theor Biol 1982, 99: 629–644. 10.1016/0022-5193(82)90191-6

  89. 89.

    Chothia C: The nature of the accessible and buried surfaces in proteins. J Mol Biol 1976, 15: 1–12. 10.1016/0022-2836(76)90191-1

  90. 90.

    Bigelow CC: On the average hydrophobicity of proteins and the relation between it and protein structure. J Theor Biol 1967, 16: 187–211. 10.1016/0022-5193(67)90004-5

  91. 91.

    Charton M: Protein folding and the genetic code: an alternative quantitative model. J Theor Biol 1981, 91: 115–373. 10.1016/0022-5193(81)90377-5

  92. 92.

    Dayhoff H, Calderone H: Composition of proteins. Atlas of Protein Sequence and Structure 1978, 5: 363–373.

  93. 93.

    Moreau G, Broto P: Autocorrelation of molecular structures, application to SAR studies. Nour J Chim 1980, 4: 757–767.

  94. 94.

    Moran PAP: Notes on continuous stochastic phenomena. Biometrika 1950, 37: 17–23.

  95. 95.

    Geary RC: The contiguity ratio and statistical mapping. Incorp Statist 1954, 5: 115–145. 10.2307/2986645

  96. 96.

    Cai YD, Liu XJ, Xu X, Chou KC: Support vector machines for prediction of protein subcellular location by incorporating quasi-sequence-order effect. J Cell Biochem 2002, 84(2):343–348. 10.1002/jcb.10030

  97. 97.

    Chou KC, Cai YD: Using functional domain composition and support vector machines for prediction of protein subcellular location. J Biol Chem 2002, 277: 45765–45769. 10.1074/jbc.M204161200

  98. 98.

    Jones DD: Amino acid properties and side-chain orientation in proteins: a cross correlation approach. J Theor Biol 1975, 50: 167–183. 10.1016/0022-5193(75)90031-4

  99. 99.

    Hopp TP, Woods KR: Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci USA 1981, 78: 3824–3828. 10.1073/pnas.78.6.3824

  100. 100.

    Feng ZP: An overview on predicting the subcellular location of a protein. In Silico Biol 2002, 2: 291–303.

  101. 101.

    Burges CJC: A tutorial on support vector machines for pattern recognition. Data Min Knowl Dis 1998, 2(2):121–167. 10.1023/A:1009715923555

  102. 102.

    Baldi P, Brunak S, Chauvin Y, Andersen CA, Nielsen H: Assessing the accuracy of prediction algorithms for classification: an overview. Bioinformatics 2000, 16(5):412–424. 10.1093/bioinformatics/16.5.412

  103. 103.

    Roulston JE: Screening with tumor markers: critical issues. Mol Biotechnol 2002, 20(2):153–162. 10.1385/MB:20:2:153

  104. 104.

    Provost F, Fawcett T, Kohavi R: The case against accuracy estimation for comparing induction algorithms. In Proc 15th International Conf on Machine Learning. San Francisco, California , Morgan Kaufmann; 1998:445–453.

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  1. Department of Pharmacy, National University of Singapore, Blk S16, Level 8, 08-14, 3 Science Drive 2, Singapore, 117543, Singapore
    • Serene AK Ong
    • , Hong Huang Lin
    •  & Yu Zong Chen
  2. College of Chemistry, Sichuan University, Chengdu, 610064, P.R. China
    • Ze Rong Li
  3. Shanghai Center for Bioinformatics Technology, 100, Qinzhou Road, Shanghai, 200235, P.R. China
    • Zhiwei Cao
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Authors' contributions

SAK generated the datasets, carried out the calculations and drafted the manuscript, HH generated the datasets and participated in the design of the study, ZR updated the descriptor generation program to calculate PseAA descriptors (ZR wrote the original descriptor generation program, introduced in previous works), YZ conceived of the study and corrected the manuscript, and YZ and ZW oversaw the design and coordination of this work and provided invaluable advice. All authors read and approved the final manuscript.

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Ong, S.A., Lin, H.H., Chen, Y.Z. et al. Efficacy of different protein descriptors in predicting protein functional families. BMC Bioinformatics 8, 300 (2007). https://doi.org/10.1186/1471-2105-8-300

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Keywords

  • Support Vector Machine
  • Amino Acid Composition
  • Matthews Correlation Coefficient
  • Amino Acid Type
  • Support Vector Machine Classification

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