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DAMpred for Recognizing Disease-Associated SNP Mutations


DAMpred is a method for predicting Disease-associated mutations of proteins in the human genome. A novel training method integrates Bayes classification and artificial neutral network to comprehensively consider sequence-based, biological assembly-based and I-TASSER model-based features and their corresponding probability density on disease-associated dataset and neutral dataset, respectively.

Figure 1 shows the Flowchart of DAMpred for disease-associated mutation prediction. All the features of DAMpred are derived from protein sequence, so its ability to deliver good predictions without experimental structure high-quality extend the application of disease-associated mutation prediction.



Figure 1: The flowchart of DAMpred method.

The DAMpred algorithm was tested on a set of 10,634 mutations from 2,154 proteins. After excluding homologous templates with sequence identity >30% to the target, I-TASSER was able to build correct structure model with a TM-score > 0.5 for 1,863 proteins. Using the I-TASSER model, DAMpred classifies all mutation into two groups, neutral and disease-associated, with an ACC 0.800 and MCC 0.601 in the protein-level 10-fold cross-validation. DAMpred improve 17% on average MCC, indicating that DAMpred give more balanced accuracy, especially for neutral mutations, compared with others methods.


How to use Molde: Single-point mutations

  • First step: Please copy and paste your data (Note: DAMpred with sequence in FASTA format will run I-TASSER to get 3D structure, which will take more time).
      Either sequence in FASTA format is acceptable:
      KLHKEPATLIKAIDGDTVKLMYKGQPMTFRLLLVDTPETKHPKKGVEKYGPEASAFTKKM
      VENAKKIEVEFDKGQRTDKYGRGLAYIYADGKMVNEALVRQGLAKVAYVYKPNNTHEQHL
      RKSEAQAKKEKLNIWS
  • Second step: Please input a list of mutations (one per mutation set per line with single-point mutations set out off by semicolons, WT residue followed by the position of the mutation followed by the mutated residue). Example,
      L20A; -Single mutation Lys, the 1th residue, is mutated to Ala
      K105M;
  • Last step: You will get the results as shown (>> Example of Output ...).


    References:
    • Lijun Quan, Hongjie Qu, Qiang Lyu, Yang Zhang. DAMpred: Recognizing disease-associated nsSNP mutations through Bayes-guided neural-network model built on low-resolution structure prediction of proteins and protein-protein interactions, submitted (2018).


    Back to DAMpred

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