Predicted as transTable 2. Benchmarking of prediction methods using the BS1.Model CS-AMPPred Linear CS-AMPPred Polynomial CS-AMPPred Radial ANFIS CAMP SVM CAMP Discriminant Analysis CAMP Random Forest SVM doi:10.1371/journal.pone.0051444.tSensitivity 89.33 94.67 94.67 94.67 93.33 98.67 90.67 84.Specificity 89.33 85.33 85.33 76.00 78.67 70.67 61.33 26.Accuracy 89.33 90.00 90.00 85.33 86.00 84.67 76.00 55.PPV 89.33 86.59 86.59 79.78 81.40 77.08 70.10 53.MCC 0.79 0.80 0.80 0.72 0.73 0.72 0.54 0.Reference This work This work This work [25] [23] [23] [23] [20]CS-AMPPred: The Cysteine-Stabilized AMPs PredictorTable 3. Benchmarking of prediction methods using the BS2.Model CS-AMPPred Linear CS-AMPPred Polynomial CS-AMPPred Radial ANFIS CAMP SVM CAMP Discriminant Analysis CAMP Random Forest SVM doi:10.1371/journal.pone.0051444.tSensitivity 69.81 77.36 79.25 100.00 88.68 90.57 96.23 98.Specificity 92.45 90.57 90.57 100.00 96.23 98.11 0.00 67.Accuracy 81.13 83.97 84.91 100.00 92.45 94.34 48.11 83.PPV 90.24 89.13 89.37 100.00 95.92 97.96 49.04 75.MCC 0.64 0.69 0.70 1.00 0.85 0.89 20.14 0.Reference This work This work This work [25] [23] [23] [23] [20]membrane portions [20,25]. In this work, a subset of PDB was used as a negative data set, since the proteins in PDB are overall more curated than in other databases. The construction of the NS was done in three steps. First, the proteins from PDB were selected by searching for the term “NOT Antimicrobial”; second, the redundant sequences were removed with a cutoff of 40 of identity, ensuring that the non-redundant sequences represent a large sample space; and the last step was randomly selecting 385 sequences to compose the 18297096 NS, avoiding an imbalance between NS and PS. In the case of CS-AMPPred, a NS composed of non79983-71-4 site antimicrobial peptides with a similar number of cysteine residues would be ideal for validating it. However, there is no warranty that a peptide has no antimicrobial activity, unless it had been already screened against several microorganisms. In the case of parigidinbr1, it does not show bactericidal activity, but it was not tested as fungicidal [8]. Another problem involved in antimicrobial activity prediction is the size variation of the sequences. In this study, the sequences in PS can vary from 16 to 90 amino acid residues. To solve this problem two strategies have been proposed, (i) the use of a fixed length of amino acids [21] and (ii) the use of physicochemical properties as sequence descriptors [20,23,24]. Here, nine structural/physicochemical properties were chosen as sequence descriptors and then reduced to five descriptors by means of PCA (Figure 1). The final descriptors were average hydrophobicity, average charge, flexibility, and indexes of a-helix and loop MedChemExpress MC-LR formation (Figures 1b and 2). In addition, a two-sided WilcoxonMann-Whitney non-parametric test was applied to verify statistical differences between PS and NS (Figure 2). The test indicates that there are differences between the sets. Similar results wereobserved by Torrent et al. [24]. These descriptors were chosen according to properties commonly related to AMPs, such as hydrophobicity and charge [20,23,25]. However, some descriptors can have the same behavior of others or even be expressionless, as observed for the hydrophobic moment (Figure 1). Therefore the PCA was done in order to select the descriptors strongly related to cysteine-stabilized antimicrobial peptides. It is important to highlight that the use of ne.Predicted as transTable 2. Benchmarking of prediction methods using the BS1.Model CS-AMPPred Linear CS-AMPPred Polynomial CS-AMPPred Radial ANFIS CAMP SVM CAMP Discriminant Analysis CAMP Random Forest SVM doi:10.1371/journal.pone.0051444.tSensitivity 89.33 94.67 94.67 94.67 93.33 98.67 90.67 84.Specificity 89.33 85.33 85.33 76.00 78.67 70.67 61.33 26.Accuracy 89.33 90.00 90.00 85.33 86.00 84.67 76.00 55.PPV 89.33 86.59 86.59 79.78 81.40 77.08 70.10 53.MCC 0.79 0.80 0.80 0.72 0.73 0.72 0.54 0.Reference This work This work This work [25] [23] [23] [23] [20]CS-AMPPred: The Cysteine-Stabilized AMPs PredictorTable 3. Benchmarking of prediction methods using the BS2.Model CS-AMPPred Linear CS-AMPPred Polynomial CS-AMPPred Radial ANFIS CAMP SVM CAMP Discriminant Analysis CAMP Random Forest SVM doi:10.1371/journal.pone.0051444.tSensitivity 69.81 77.36 79.25 100.00 88.68 90.57 96.23 98.Specificity 92.45 90.57 90.57 100.00 96.23 98.11 0.00 67.Accuracy 81.13 83.97 84.91 100.00 92.45 94.34 48.11 83.PPV 90.24 89.13 89.37 100.00 95.92 97.96 49.04 75.MCC 0.64 0.69 0.70 1.00 0.85 0.89 20.14 0.Reference This work This work This work [25] [23] [23] [23] [20]membrane portions [20,25]. In this work, a subset of PDB was used as a negative data set, since the proteins in PDB are overall more curated than in other databases. The construction of the NS was done in three steps. First, the proteins from PDB were selected by searching for the term “NOT Antimicrobial”; second, the redundant sequences were removed with a cutoff of 40 of identity, ensuring that the non-redundant sequences represent a large sample space; and the last step was randomly selecting 385 sequences to compose the 18297096 NS, avoiding an imbalance between NS and PS. In the case of CS-AMPPred, a NS composed of nonantimicrobial peptides with a similar number of cysteine residues would be ideal for validating it. However, there is no warranty that a peptide has no antimicrobial activity, unless it had been already screened against several microorganisms. In the case of parigidinbr1, it does not show bactericidal activity, but it was not tested as fungicidal [8]. Another problem involved in antimicrobial activity prediction is the size variation of the sequences. In this study, the sequences in PS can vary from 16 to 90 amino acid residues. To solve this problem two strategies have been proposed, (i) the use of a fixed length of amino acids [21] and (ii) the use of physicochemical properties as sequence descriptors [20,23,24]. Here, nine structural/physicochemical properties were chosen as sequence descriptors and then reduced to five descriptors by means of PCA (Figure 1). The final descriptors were average hydrophobicity, average charge, flexibility, and indexes of a-helix and loop formation (Figures 1b and 2). In addition, a two-sided WilcoxonMann-Whitney non-parametric test was applied to verify statistical differences between PS and NS (Figure 2). The test indicates that there are differences between the sets. Similar results wereobserved by Torrent et al. [24]. These descriptors were chosen according to properties commonly related to AMPs, such as hydrophobicity and charge [20,23,25]. However, some descriptors can have the same behavior of others or even be expressionless, as observed for the hydrophobic moment (Figure 1). Therefore the PCA was done in order to select the descriptors strongly related to cysteine-stabilized antimicrobial peptides. It is important to highlight that the use of ne.
