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Bioinformatics. 2010 September 15; 26(18): i467–i473.
Published online 2010 September 4. doi:  10.1093/bioinformatics/btq371
PMCID: PMC2935422

Solenoid and non-solenoid protein recognition using stationary wavelet packet transform

An Vo,1,* Nha Nguyen,2, and Heng Huang3


Motivation: Solenoid proteins are emerging as a protein class with properties intermediate between structured and intrinsically unstructured proteins. Containing repeating structural units, solenoid proteins are expected to share sequence similarities. However, in many cases, the sequence similarities are weak and non-detectable. Moreover, solenoids can be degenerated and widely vary in the number of units. So that it is difficult to detect them. Recently, several solenoid repeats detection methods have been proposed, such as self-alignment of the sequence, spectral analysis and discrete Fourier transform of sequence. Although these methods have shown good performance on certain data sets, they often fail to detect repeats with weak similarities. In this article, we propose a new approach to recognize solenoid repeats and non-solenoid proteins using stationary wavelet packet transform (SWPT). Our method associates with three advantages: (i) naturally representing five main factors of protein structure and properties by wavelet analysis technique; (ii) extracting novel wavelet features that can capture hidden components from solenoid sequence similarities and distinguish them from global proteins; (iii) obtaining statistics features that capture repeating motifs of solenoid proteins.

Results: Our method analyzes the characteristics of amino acid sequence in both spectral and temporal domains using SWPT. Both global and local information of proteins are captured by SWPT coefficients. We obtain and integrate wavelet-based features and statistics-based features of amino acid sequence to improve the classification task. Our proposed method is evaluated by comparing to state-of-the-art methods such as HHrepID and REPETITA. The experimental results show that our algorithm consistently outperforms them in areas under ROC curve. At the same false positive rate, the sensitivity of our WAVELET method is higher than other methods.


Contact: ude.atu.svam@ov.uhncouhpna


With several interesting features of repeating sequences, significant progress has been made in the identification of the DNA and protein repeats, understanding the duplication mechanism and special features of the repeat evolution (Kajava, 2001). Repeats are usually found in non-coding genomic regions. However, repeating sequences are also found in about 14% of all proteins coded by all known genes with about 25% of all eukaryotic proteins (Marcotte et al., 1999). The known protein structures can be classified by the length of their repeats, which can provide information about a possible 3D structure of the repetitive protein (Kajava, 2001). There are four main structural classes (Kajava, 2001): Class I, crystalline structures (1- to 2-residue repeats); Class II, fibrous proteins (3- to 4-residue repeats); Class III, solenoid proteins (5- to 42-residue repeats); and Class IV, domain-forming repeats (30 or more residues). Solenoid proteins contain a superhelical arrangement of repeating structure units (Kobe et al., 2000). This arrangement contrasts the structure of most Class-IV proteins that fold into globular domains in more complex manners.

Repeats in Class I and Class II have only 1−4 residues, hence they have low sequence complexity and can be easily detected. Globular repeats in Class IV have their sufficient length to be detected by database search tools like PSI-BLAST (Altschul et al., 1997). Solenoid proteins are built of repeated structural units. The repeating units of the solenoids consist of one to several segments of secondary structure, among which are α-helices (Kajava et al., 2002), β-strands (Hennetin et al., 2006) and 310-helices. The solenoid proteins have purely α-helices or β-strands or a mixture of the secondary structures (Kobe et al., 2000). They are expected to share sequence similarities. However, in some cases, the sequence similarities are weak such as protein farnesyltransferase (FTase; (Boguski et al., 1992) and insulin-like growth factor-1 receptor (IGF-1R; Bajaja et al., 1987), so that they are non-detectable (Kobe et al., 2000). Therefore, database search tools like PSI-BLAST relying on clear conservation pattern are not good tools to detect solenoid repeats.

In recent years, several methods have been proposed to identify solenoid repeats. Some of them are based on self-alignment of the sequence such as REPRO (George et al., 2000), RADAR (Heger et al., 2000), TRUST (Szklarczyk et al., 2004), HHrep (Soding et al., 2006) and HHrepID (Biegert et al., 2008). HHrep and HHrepID utilized hidden Markov model comparison (HMM–HMM), while the others used sequence–sequence comparison to find suboptimal self-alignments. Repeating parts of the sequence appear as off-diagonal regions of similarity. They allow the detection of basic repeating units and locations of units along the sequence. HHrepID has been reported to be the most sensitive self-alignment approach to detect repeats (Biegert et al., 2008). However, HHrepID often cannot detect repeats with weak similarities.

Other approaches to recognize solenoid repeats use periodic patterns in proteins such as (Coward et al., 1998), (Murray et al., 2002), (Murray et al., 2004), REPPER (Gruber et al., 2005) and REPETITA (Marsella et al., 2009). Repeating protein motifs, TIM barrels, propellor blades, coiled coils and leucine-rich repeating structures have been analyzed (Murray et al., 2002) and used to detect repeats in known protein structure. The data utilized in Murray et al. (2002) are relative accessible surface area and simple hydrophobicity that provide information of the protein structure and sequence. REPPER (Gruber et al., 2005) searches for periodicities of particular, user-defined types (hydrophobic, polar, positively charged) using the Fourier transform of sequence. However, it primarily aims at the analysis of fibrous proteins and does not allow insertions between repeating units. REPETITA (Marsella et al., 2009) utilizes sequence profile with the discrete Fourier transform to detect degenerated repeats (Lupas et al., 1997). It includes the five numeric scales proposed by Atchley (Atchley et al., 2005) to characterize the amino acid sequence. Compared to TRUST and RADAR, REPETITA has been reported to be more sensitive. However, similar to HHrepID, REPETITA also cannot detect some repeats with weak similarities.

Wavelet analysis has been widely applied to process biomedical signals (Unser et al., 1996). Some applications of wavelet transforms in genome sequence analysis and gene expression data analysis have been proposed (Li, 2003). A key advantage of wavelet transforms over the Fourier transform is their ability to simultaneously capture both spectral and temporal information within the signal (Daubechies, 1992, Mallat et al., 1989). In contrast, the Fourier transform does not give local information of proteins, because the Fourier coefficients only contain globally averaged information. Wavelet analysis has an improved ability to capture hidden components from biological data and is a good link between biological systems and the mathematics objects (Li, 2003). The wavelet transforms can be categorized as: continuous wavelet transform (CWT) and discrete wavelet transform (DWT). The CWT was used to detect and characterize repeating motifs in protein sequence and structure data (Murray et al., 2002). It maps a signal to a time-scale joint representation calculated by continuously shifting a continuously scalable function over a signal and calculating the correlation between them. The resulting wavelet coefficients are highly redundant. In molecular biology and genetics, we are more interested in discretely sampled rather than continuous functions. The DWT was used to classify protein subcellular location images (Chebira et al., 2007). Stationary wavelet packet transform (SWPT) is one of discrete wavelet analysis techniques. A main advantage of the stationary wavelets over the DWT is its shift invariant property (Coifman et al., 1995). The SWPT is suitable for many bioinformatics applications, such as DNA copy numbers smoothing and detection (Huang et al., 2008; Nguyen et al., 2010).

In this article, the SWPT technique is proposed to characterize proteins by five representation factors: polarity, secondary structure, molecular volume, codon diversity and electrostatic charge. We propose to extract new features from the SWPT of five factors and from statistics of amino acid sequence, and employ them to classify solenoid and non-solenoid proteins. Empirical studies on solenoid protein detection have been performed to compare proposed method to other related methods. Experimental results demonstrate the promising performance of our proposed approach.


A flow diagram with all steps of our algorithm is given in Figure 1. The individual steps including wavelet analysis technique, feature extraction, feature selection, and classification will be described in following subsections.

Fig. 1.
The block diagram of WAVELET method for solenoid and non-solenoid classifications. Novel statistics-based and wavelet-based features are the key components of our proposed method.

2.1 The proposed method

The framework of proposed method is shown in Figure 1. At first, a protein sequence is translated into five numerical signals derived by Atchley (Atchley et al., 2005). These five signals represent polarity, secondary structure, molecular volume, codon diversity and electrostatic charge. All signals are normalized to zero mean, since the averages are not significant to detect repeats. Next, each signal is decomposed into 16 subbands by SWPT wavelet transform (see Section 2.2). Eighty subbands obtained from five signals are used to extract eighty wavelet features as in Equation (5). In addition to wavelet features, probability features of 20 amino acids are also computed for each protein sequence. Seventeen features are selected from total 100 features using the forward feature selection method. Finally, the quadratic discriminant classifier described in Section 2.5 is applied to classify protein sequences.

Inspired by wavelet analysis for the protein structure and sequence (Murray et al., 2002), we propose to use the SWPT to analyze characteristics of amino acid sequence. However, there are two main differences between Murray's method and ours. The first difference is that the data utilized in Murray et al. (2002) is relative accessible surface area and simple hydrophobicity, while the data utilized in our method is five patterns that summarize a large portion of the physio-chemical and biological properties of amino acids (Atchley et al., 2005; Marsella et al., 2009). To obtain these five factors, 495 amino acid indices which include general attributes, such as molecular volume or size, hydrophobicity and charge, as well as more specific measures, such as the amount of nonbonded energy per atom or side chain orientation angle are analyzed. This analysis simplifies high-dimensional data by generating a smaller number of factors that would summarize the entire constellation of amino acid physiochemical properties. The resultant factors are linear functions of the original data, are fewer in number than the original, and reflect clusters of covarying traits that describe the underlying or latent structure of the variables. The first resultant factor is a polarity index which is bipolar, large positive and negative factor coefficients and also reflects simultaneous covariance in portion of polarity versus nonpolarity, and hydrophobicity versus hydrophilicity. Therefore, the hydrophobicity feature used in the previous study is also involved in the first factor. The second difference is that Murray (Murray et al., 2002) used the continuous wavelets which are highly redundant, but we are more concerned with discrete sampling rather than continuous functions for protein sequence representation. Moreover, since some amino acids play important roles in structure of solenoids, we propose statistics features to capture repeating motifs of solenoids.

2.2 Stationary wavelet packet transform

The SWPT is based on filters H1 and G1 and on an up-sampling operator. The filter H1 is a low-pass filter defined by a sequence h1(n) and the high-pass filter G1 defined by a sequence g1(n). Given a signal s(n) of length Ns, the first level of the SWPT produces two subbands: approximation subband s11(n) and detail subband s12(n). These subbands are obtained by convolving s(n) with the low-pass filter h1(n), and with the high-pass filter g1(n) as follows:

equation image

Sequences h1(n) and g1(n) are obtained by using MATLAB function wfilters where n is an integer. An example of h1(n) and g1(n) is given by h1(n) = {−0.1294, 0.2241, 0.8365, 0.4830} and g1(n) = {−0.4830, 0.8365, −0.2241, −0.1294} when db2 wavelets are used. Values of k in the above summation are from 1 to Ns, where Ns is the length of s(n). Two new subbands s11 and s12 have the same length as the original signal s(n). The low-pass filter H1 is assumed to satisfy the internal orthogonal relation as

equation image

for all integers i ≠ 0 and ∑nh12(n) = 1. The high-pass filter G1 is defined by

equation image

The high-pass filter G1 satisfies the same internal orthogonal relation as H1 and the mutual orthogonal relation as

equation image

for all integers i. For further details of these filters, please see Daubechies (1992) and Mallat et al. (1989).

The filters are modified at each level by an up-sampling operator. The filter hl(n) at level l is obtained by inserting a zero between every adjacent pair of elements of the filter hl−1(n) at level (l − 1), and similarly for filter gl(n) (Nason et al., 1995). Each filter is an upsampled version of the previous one. The second level of the SWPT produces four subbands: s21(n),···, s24(n). These subbands are obtained by convolving s11(n) and s12(n) with the filters h2(n) and g2(n). The process is iterated until an expected level l is reached. The number of subbands at level l is equal to 2l. For example, in order to obtain the SWPT with 16 subbands, we select l = 4 because 24 = 16. We calculate h2(n) and g2(n) by inserting one zero between samples of h1(n) and g1(n). Similarly, we compute h3(n), g3(n) and h4(n), g4(n) by inserting one zero between samples of h2(n), g2(n) and h3(n), g3(n).

The SWPT does not employ a decimator after filtering. The absence of a decimator leads to a full rate decomposition. Each subband contains the same number of samples as the input. The absence of a decimator makes the SWPT shift invariant. This shift invariant property provides the SWPT preferable for the usage in various signal processing applications such as smoothing (Huang et al., 2008; Nguyen et al., 2010) and classification because they capture more spatial information. It has been shown that many of the artifacts could be suppressed by a redundant representation of the signal (Coifman et al., 1995). The SWPT offers a richer range of possibilities for signal analysis. Thus, we propose to use the SWPT to analyze characteristics of proteins. In our experiments, a signal was decomposed into 16 subbands corresponding to with four-level SWPT. The numbers of subbands and filter type were chosen to give the best results in classification performance. We applied several l-level SWPTs with l = 2, 3, 4, 5 and several types of filters. The four-level SWPT and Coif5 filter produce the best results. From wavelet subbands how to generate features for solenoid classifier will be described in the next subsection.

2.3 Feature extractions

2.3.1 Wavelet feature extraction

A solenoid protein comprises repeating structural units that arrange to let the polypeptide chain form a continuous superhelix (Kobe et al., 2000). It is expected to share sequence similarities. However, in some cases, the sequence similarities are weak, so that they are non-detectable. The knowledge of the structure can help the detections of weak sequence similarities and patterns among the structure units. The set of five factors derived by Atchley was used in analysis directed toward understanding the structural and functional aspects of protein variability. Factor II presents the secondary structure. There is an inverse relationship of relative propensity for various amino acids in various secondary structural configurations, such as a coil, a turn, or a bend versus the frequency in an α-helix (Atchley et al., 2005).

Instead of using the discrete Fourier transform (DFT; Marsella et al., 2009) for five factors combined with sequence profiles, we use the SWPT to analyze these five factors. It should be noted that the Fourier transform result is a global measure. Therefore, the period obtained from DFT method is a global period which could be invisible in many solenoids. In contrast, the SWPT analysis can capture hidden components from sequence similarities.

Each signal (factor) is decomposed into 16 subbands by SWPT. The energy of each subband is calculated by

equation image

where k = 1, 2,···, 16, sk(i) are the k-th subband coefficients and Ns is the number of coefficients.

Each sequence is presented by five factors. As a result, we obtain 80 wavelet-based features for each protein sequence. The wavelet-based features of factor II extract the knowledge of the structure that can help weak sequence similarities detection. The wavelet-based features of other factors extract physio-chemical and biological properties of amino-acid sequence. Besides wavelet features, we also propose to use statistical information of amino acids in protein sequences for generating protein features.

2.3.2 Statistical feature extraction

Solenoid proteins contain a superhelical arrangement of repeating structural units. The most common arrangement of the solenoid proteins is a single-stranded superhelix which is formed by one or several elements of secondary structure (such as α-helices, β-strands and 310-helices) winding along the superhelical axis. Each repeat contains at least one turn with an irregular conformation introduced between the secondary structures. The minimal structural unit corresponding to one repeat has one secondary structure element and one turn. Several representative structural repeating motifs are summarized below, where the asterisk denotes a polar residue, o denotes nonpolar residues, and x is any residue.

  • A-(N/D)-L-*-x: the pentapeptide repeat protein (Bateman et al., 1998); S-x-(V/I)-x-G: the pentapeptide repeat of anti-freeze protein (Graether et al., 2000) contains one β-strand and one turn. Pentapeptide repeat proteins (PRPs) are found primarily in bacteria, especially cyanobacteria. Although the structure of the cyanobacterial pentapeptide proteins is not yet available, PRPs have important biochemical and physiological functions in cyanobacteria. The newly uncovered structural features may help scientists discover the biological role of pentapeptide repeat proteins within the cell.
  • SxIGxx: the hexapeptide repeat of LpxA (Raetz et al., 1995) contains one β-strand and one turn. In hexapeptide, the regular superhelical surface of the β-helices might prefer to satisfy the protein-interacting demand by forming homo-oligomers (Kobe et al., 2000).
  • DxLxGGxGx: the nine-residue repeat of serralysin (Baumann et al., 1993) contains one β-strand and one turn shown in Figure 2c.
    Fig. 2.
    Examples of consensus motifs in solenoid proteins. (a) Leucine-rich repeat (LRR), (b) Leucine-rich repeat variant (LRV), (c) Serralysin, (d) Protein FTase, (e) Insulin-like growth factor-1 receptor L domain (IGF-1R L) and (f) HEAT. Positions of α-helices ...
  • xxxGoxxLxxoLxxxxxLxxLxLxxNxL: the LRR of ribonuclease inhibitor (RI); LxxLxLxxN/CxL: the 11-residue repeat of the LRRs contains a β-strand and an α-helix (Kajava, 1998) as shown in Figure 2a. LRR proteins appear in different proteins with diverse functions. They bind a number of globular proteins by their concave surface. In the RI molecule, structural units consisting of a β-strand and an α-helix are arranged so that all the β-strands and the helices are parallel to a common axis, resulting in a nonglobular, horseshoe-shaped molecule with a curved parallel β-sheet lining the inner circumference of the horseshoe and the helices flanking its outer circumference (Kajava, 2001).
  • xxxxxxxxLLPxLxxxxxDxxxxVRxxxxxxLxxLxxxx: the HEAT repeat of PR65/A subunit (Groves et al., 1999). The HEAT repeats (Andrade et al., 1995) have two anti-parallel α-helices and make one complete coil shown in Figure 2f. They contain nuclear import factor importin-β used when conformational adjustment to the binding partners are needed (Kobe et al., 2000).
  • Leucine-rich repeat variant (LRV) (Peters et al., 1996) contains an α-helix and 310-helix as shown in Figure 2b.
  • Protein FTase α-subunit (Boguski et al., 1992) is shown in Figure 2d.
  • Insulin-like growth factor-1 receptor L domain (IGF-1R L) (Bajaja et al., 1987) contains β-strands as shown in Figure 2e. The sequence similarities in IFG-1R and FTase are weak.

From above structural repeating motifs, some amino acids play key roles in structure of solenoids. Therefore, we propose using amino acid compositions as additional features to capture repeating motifs of solenoid proteins as follows

equation image

where X = [A, C, D, E, F,···, V, W, Y] is the one-letter code corresponding to each of the 20 amino acids, and NX is the number of amino acids X in a sequence, and Ns is the length of that sequence. The 80 wavelet-based features and 20 statistics-based features are combined, resulting a total of 100 features for each protein sequence. We can use all 100 features as inputs of a classifier. However, because the number of features is larger than the number of classes, one of the ways to select features is using forward selection.

2.4 Feature selection

The forward feature selection procedure (Kohavia et al., 1997) starts by evaluating all feature subsets, which consist of only one feature. We obtain 100 models at this point and the model that performs the best is chosen. The feature subset now contains one feature. Next, forward selection finds the best subset consisting of two features. Ninenty nine feature subsets are made by pairing this chosen feature with all the remaining 99 features, one by one. For 99 models, their statistics are compared to select the best performing model. The feature subset now contains two features. These iterations are continued until the best classification accuracy is obtained.

As a result, 17 features which include eight wavelet-based features and nine statistics-based features are selected from a total of 100 features using the forward feature selection method. Tables 1 and and22 show more details of selected features. All five factors which describe structure and properties of protein are present in selected feature subset at different subbands as in Table 1. The first row shows feature number (1–100). The first 80 features are from wavelet-based features and the last 20 features are from amino acid compositions. The second and third rows present factor (I–IV) and subband number (1–16). Statistical features of amino acids in sequence are also selected in Table 2. The selected feature corresponding to the occurrence frequency of amino acid L in sequences makes more sense with structural repeating motifs summarized in the previous subsection. After selecting a set of good features, we use them as inputs of a classifier described in the next subsection.

Table 1.
Selected wavelet features from a total of 100 features using the forward feature selection method
Table 2.
Selected statistics features from a total of 100 features using the forward feature selection method

2.5 Classification

In our experiment, we use a quadratic discriminant analysis classifier (QDA; Krzanowski, 1988), which is a standard supervised classification approach. QDA models the likelihood of each class as a Gaussian distribution. The posterior distributions are used to estimate the class for a given test point. We can use maximum likelihood estimation algorithm to estimate the Gaussian parameters for each class from training points. A MATLAB function, classify.m in Statistics toolbox is used to perform QDA classification. A setting for this function is quadratic type. Feature vectors are normalized to have a unit variance before classification step. Some other complex classification methods may also be applied to further improve the classification results. However, this is beyond the scope of the paper and might smear the effect of the proposed features.


3.1 Data sets

Two groups of data are studied: (i) 105 solenoid repeat proteins; (ii) 247 globular proteins (non-solenoid) without structural repeat. These data are downloaded from the website ( of the previous study (Marsella et al., 2009). Marsella took an initial set of 32 proteins with solenoid repeats and used the TESE server (Sirocco, 2008) to find more protein domains belonging to the same solenoid folds as the initial set. By limiting the maximal residual structural similarity according to the CATH classification (Pearl et al., 2003), TESE allows the user to generate ad hoc non-redundant sets of proteins with known structure. The final set of 105 solenoid domains was yielded by choosing representatives with at most 35% pairwise sequence identity (i.e. CATH ‘S’ level). Marsella also generated the set of 247 non-solenoid protein domains with TESE by randomly choosing X-ray structures with different topologies and no detectable sequence similarity (i.e. CATH ‘T’ level). A training set of 50 solenoid proteins and 119 non-solenoid, and a testing set of 55 solenoid proteins and 128 non-solenoid ones are selected as in Marsella et al. (2009). The solenoid proteins contain the main repeat classes such as all α, all β, and α/β with available structure information or they have their structures and evolutions related to these major folds.

Sequences are composed of long strings of alphabetic letters rather than arrays of numerical values. A metric for comparing such alphabetic data is sophisticated. Therefore, a method proposed by Atchley (Atchley et al., 2005) to quantify alphabetic information inherent to biological sequences was applied. Five patterns that summarize a large portion of the physio-chemical and biological properties of amino acids were obtained. These five factors represent polarity, secondary structure, molecular volume, codon diversity and electrostatic charge.

3.2 Comparisons to existing methods

We compare the classification performance of our WAVELET method against four exiting methods in protein repeats detection: RADAR (Heger et al., 2000), TRUST (Szklarczyk et al., 2004), HHrepID (Biegert et al., 2008) and REPETITA (Marsella et al., 2009). Sensitivity, specificity and accuracy of all methods are computed for training set, testing set and overall data.

RADAR and TRUST detect internal sequence symmetries by comparing the protein sequence itself and utilize sequence–sequence comparison to find suboptimal. RADAR builds a repeat profile to determine exact borders and extract a multiple alignment of repeats self-alignments, and TRUST explicitly makes use of consistency that has led to improvements in multiple sequence alignment. In TRUST and RADAR methods, predictions are considered when at least two repeat units are detected.

HHrepID utilizes hidden Markov model comparison. The maximum expected accuracy algorithm that maximizes the sum of posterior probabilities in the alignment and a probabilistic approach to consistency through a merging procedure based on posterior probabilities are also applied. HHrepID has been reported to be most sensitive to date (Biegert et al., 2008). We use default settings for HHrepID method. The MAC threshold is set to 0.5 and the P-value threshold for suboptimal alignment is set to 0.1.

REPETITA detects solenoid repeats and discriminates them from globular proteins using information from sequence profiles together with the discrete Fourier transform, based on the assumption that few characteristics of sequence repeats uniquely identify structural repeats.

3.3 Results and discussions

We summarize experimental results including sensitivity, specificity and accuracy in Table 3. Data sets used for evaluations are the training set, testing set and overall data. We evaluate both training set and testing set to verify that our predictive model does not overfit the training data. Because our model fits both training set and test set well with the accuracy of 94.1% and 91.3%, respectively, non-overfitting has taken place. Table 3 shows the optimal results of each method. The sensitivity and accuracy of our WAVELET method are consistently higher than the HHrepID and REPETITA methods for all three metrics. In overall data, the WAVELET method yields the best sensitivity of 93.3%, while the sensitivity of HHrepID and REPETITA methods are 66.7% and 70.0%, respectively.

Table 3.
Comparisons of HHrepID, REPETITA and WAVELET methods for solenoid detection

We evaluate all methods using ROC curve as shown in Figure 3. The number of true positive solenoid proteins against the number of false positive proteins detected above a threshold significance is computed. In the case of HHrepID method, we used the total repeat P-value for the threshold significance. The signed distance from the optimal line is used for significance measure in REPETITA method. For RADAR and TRUST methods, the number of repeat units is used. Predictions are considered where at least two repeat units have been detected. In our method, we use the posterior probabilities obtained from the QDA classifier for threshold significance. The performances of all methods in terms of areas under the ROC curve are shown in Table 4 when the false positive ranges from 0 to 20. The performance of WAVELET is better than other methods from 21% to 46% in areas under the ROC curve.

Fig. 3.
Comparisons of RADAR, TRUST, HHrepID, REPETITA and WAVELET methods for solenoid detection: the number of true positive solenoid proteins against the number of false positive proteins detected above a threshold significance when overall data are used.
Table 4.
Performance of all methods in terms of areas under ROC curve in overall data when false positives are from 0 to 20

At a false positive rate (FPR) of 8% (20/247), WAVELET method is able to detect about 60% more solenoid proteins than RADAR and about 50% more than REPETITA. TRUST and HHrepID can detect better than RADAR and REPETITA. However, WAVELET method performs about 37% better than TRUST and 29% better than HHrepID in sensitivity at FPR of 8%. When the FPR is from 3% to 8%, WAVELET also outperforms the others. The solenoid proteins detected using WAVELET is close to using HHrepID, when FPR is 1–3%. But they are much more than RADAR, TRUST and REPETITA. Compared to RADAR and TRUST in detecting solenoids, HHrepID is an identifier with higher sensitivity. This agrees with results reported in Biegert et al. (2008) that HHrepID is most sensitive to date. When FPR is <1%, the sensitivity of HHrepID method is higher than the others. However, the highest sensitivity of HHrepID in this simulation is about 67% for overall data, while that of WAVELET method can reach 93% at the same FDR of 8%. Because the structure information using wavelet feature is combined with statistical information in our WAVELET method, a higher classification accuracy was achieved.

Figure 4 shows the overall performances of WAVELET when the number of features changes from 1 to 17. The WAVELET's performance almost increases when the number of features increases. The accuracy of the WAVELET ranges from 77% to 93% corresponding to 1 to 17 features. In REPETITA method, only two features are used. A small number of features often cannot capture enough biological information for detection. Therefore, there are only 70% solenoid data detected by REPETITA method, while WAVELET method with 17 features can detect 93% solenoid data.

Fig. 4.
Sensitivity, specificity and accuracy of WAVELET method for solenoid and non-solenoid classification against the number of selected features. Overall data are used.

We also show some examples of RADAR, TRUST, REPETITA, HHrepID and WAVELET methods for solenoid protein detection in Table 5. These solenoid proteins are plotted in Figure 5. Three of six sample solenoids are non-detectable by RADAR and TRUST methods. REPETITA can detect four solenoids, WAVELET can detects all of six solenoids, while HHrepID cannot find any repeats in these solenoid sequences. All above simulation results illustrate that WAVELET method outperforms the others.

Fig. 5.
Examples of solenoid proteins: (a) 1p5qA02, (b) 1xat000, (c) 1ee6A00, (d) 1ho8A01, (e) 2a4zA03 and (f) 1tdtA02. Detection results of these solenoids using RADAR, TRUST, REPETITA, HHrepID and WAVELET methods are shown in Table 5. Rainbow coloring from ...
Table 5.
Examples of solenoid detection using RADAR, TRUST, REPETITA, HHrepID and WAVELET methods


In this article, we proposed a new WAVELET method to recognize solenoid proteins and global proteins using SWPT and statistical features of amino acid sequences. In order to detect solenoid repeats with weak similarities, we took advantages of the integration of wavelet-statistics features and the SWPT analysis of five factors representing protein structure and properties. Our new features can capture structure, properties of solenoid proteins and hidden components from sequence similarities, to distinguish them from global proteins. The proposed approach was validated by comparing to other state-of-the-art methods in solenoid proteins detection experiments. In all results, our new scheme improved the solenoid protein recognition in all statistical metrics, including sensitivity, specificity and accuracy. The WAVELET method is a promising approach for solenoid protein classification. Based on different types of training data, the WAVELET method can be applied to classify different kinds of solenoids or different kinds of protein structures in future work.

Funding: NSF-CCF 0830780; NSF-CCF 0939187; NSF-CCF 0917274; NSF-DMS 0915228; NSF-CNS 0923494; University of Texas Arlington Research Enhancement Program.

Conflict of Interest: none declared.


  • Altschul SF, et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389–3402. [PMC free article] [PubMed]
  • Andrade MA, et al. HEAT repeats in the Huntington's disease protein. Nat. Genet. 1995;11:115–116. [PubMed]
  • Atchley W, et al. Solving the protein sequence metric problem. Proc. Natl. Acad. Sci. USA. 2005;102:6395–6400. [PubMed]
  • Bajaja M, et al. On the tertiary structure of the extracellular domains of the epidermal growth factor and insulin receptors. Biochim. Biophys. Acta. 1987;916:220–226. [PubMed]
  • Bateman A, et al. Structure and distribution of pentapeptide repeats in bacteria. Protein Sci. 1998;7:1477–1480. [PubMed]
  • Baumann U, et al. Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two-domain protein with a calcium binding parallel beta roll motif. EMBO J. 1993;12:3357–3364. [PubMed]
  • Biegert A, et al. De novo identification of highly diverged protein repeats by probabilistic consistency. Bioinformatics. 2008;24:807–814. [PubMed]
  • Boguski M, et al. Novel repetitive sequence motifs in the alpha and beta subunits of prenyl-protein transferases and homology of the alpha subunit to the MAD2 gene product in yeast. New Biol. 1992;4:408–411. [PubMed]
  • Chebira A, et al. A multiresolution approach to automated classification of protein subcellular location images. BMC Bioinformatics. 2007;8:1–10. [PMC free article] [PubMed]
  • Coifman RR, et al. Translation invariant de-noising. Lecture Notes Stat. 1995;103:125–150.
  • Coward E, et al. Detecting periodic patterns in biological sequences. Bioinformatics. 1998;14:498–507. [PubMed]
  • Daubechies I. Ten Lectures on Wavelets (CBMS-NSF Regional Conference Series in Applied Mathematics). Society for Industrial and Applied Mathematics (SIAM); 1992. Chapter 3; pp. 53–106.
  • George RA, et al. The REPRO server: finding protein internal sequence repeats through the web. Trends Biochem. Sci. 2000;25:515–517. [PubMed]
  • Graether SP, et al. Beta-helix structure and ice-binding properties of a hyperactive antifreeze protein from an insect. Nature. 2000;406:325–328. [PubMed]
  • Groves MR, et al. Topological characteristics of helical repeat proteins. Curr. Opin. Struct. Biol. 1999;9:383–389. [PubMed]
  • Gruber M, et al. REPPER-repeats and their periodicities in fibrous proteins. Nucleic Acids Res. 2005;33:W239–W243. [PMC free article] [PubMed]
  • Heger A, et al. Rapid automatic detection and alignment of repeats in protein sequence. Proteins Struct. Funct. Genet. 2000;41:224–237. [PubMed]
  • Hennetin J, et al. Standard conformations of beta-arches in beta-solenoid protein. J. Mol. Biol. 2006;358:1094–1105. [PubMed]
  • Huang H, et al. Array CGH data modeling and smoothing in stationary wavelet packet transform domain. BMC Genomics. 2008;9:S2–S17. [PMC free article] [PubMed]
  • Kajava A, et al. What curve alpha-solenoid? J. Biol. Chem. 2002;227:49791–49798. [PubMed]
  • Kajava AV. Structural diversity of leucine-rich repeat proteins. J. Mol. Biol. 1998;277:519–527. [PubMed]
  • Kajava AV. Review: proteins with repeated sequence-structural prediction and modeling. J. Struct. Biol. 2001;134:132–144. [PubMed]
  • Kobe B, et al. When protein folding is simplified to protein coiling: the continuum of solenoid protein structures. Trends in Biochemical. Sci. 2000;25:509–515. [PubMed]
  • Kohavia R, et al. Wrappers for feature subset selection. Artificial Intelligence. 1997;97:273–324.
  • Krzanowski WJ. Principles of Multivariate Analysis: A User's Perspective (Oxford Statistical Science Series). Oxford University Press; 1988. Chapter 12; p. 340.
  • Li P. Wavelets in bioinformatics and computational biology: state of art and perspectives. Bioinformatics. 2003;19:2–9. [PubMed]
  • Lupas A, et al. Self-compartmentalizing proteases. Trends Biochem. Sci. 1997;22:399–404. [PubMed]
  • Mallat S, et al. A theory for multiresolution signal decomposition: the wavelet representation. IEEE Pattern Anal. Mach. Intell. 1989;11:674–693.
  • Marcotte EM, et al. Census of protein repeats. J. Mol. Biol. 1999;293:151–160. [PubMed]
  • Marsella L, et al. REPETITA: detection and discrimination of the periodicity of protein solenoid repeats by Fourier transform. Bioinformatics. 2009;25:i289–i295. [PMC free article] [PubMed]
  • Murray KB, et al. Wavelet transforms for the characterization and detection of repeating motifs. J. Mol. Biol. 2002;316:341–363. [PubMed]
  • Murray KB, et al. Toward the detection and validation of repeats in protein structure. Proteins. 2004;57:365–380. [PubMed]
  • Nason GP, et al. The stationary wavelet transform and some statistical applications. Lecture Notes Stat. 1995;103:281–299.
  • Nguyen N, et al. Stationary wavelet packet transform and dependent Laplacian bivariate shrinkage estimator for array-CGH data smoothing. J. Comput. Biol. 2010;17:139–152. [PubMed]
  • Pearl FM, et al. The CATH database: an extended protein family resource for structural and functional genomics. Nucleic Acids Res. 2003;31:452–455. [PMC free article] [PubMed]
  • Peters JW, et al. A leucine-rich repeat variant with a novel repetitive protein structural motif. Struct. Biol. 1996;3:1181–1187. [PubMed]
  • Raetz CR, et al. A left-handed parallel beta helix in the structure of UDP-N-acetylglucosamine acyltransferase. Science. 1995;270:997–1000. [PubMed]
  • Sirocco F, et al. TESE: generating specific protein structure test set ensembles. Bioinformatics. 2008;24:2632–2633. [PubMed]
  • Soding J, et al. HHrep: de novo protein repeat detection and the origin of TIM barrels. Nucleic Acids Res. 2006;34:W137–W142. [PMC free article] [PubMed]
  • Szklarczyk R, et al. Tracking repeats using significance and transitivity. Bioinformatics. 2004;20:i311–i317. [PubMed]
  • Unser M, et al. A review of wavelets in biomedical applications. Proc. IEEE. 1996;84:626–638.

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