A gene-specific method for predicting hemophilia-causing point mutations.
A fundamental goal of medical genetics is the accurate prediction of genotype-phenotype correlations. As an approach to develop more accurate in silico tools for prediction of disease-causing mutations of structural proteins, we present a gene- and disease-specific prediction tool based on a large systematic analysis of missense mutations from hemophilia A (HA) patients. Our HA-specific prediction tool, HApredictor, showed disease prediction accuracy comparable to other publicly available prediction software. In contrast to those methods, its performance is not limited to non-synonymous mutations. Given the role of synonymous mutations in disease and drug codon optimization, we propose that utilizing a gene- and disease-specific method can be highly useful to make functional predictions possible even for synonymous mutations. Incorporating computational metrics at both nucleotide and amino acid levels along with multiple protein sequence/structure alignment significantly improved the predictive performance of our tool. HApredictor is freely available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/HA_Predict/index.htm.
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Nobuko
N
Hamasaki-Katagiri
Raheleh
R
Salari
Andrew
A
Wu
Yini
Y
Qi
Tal
T
Schiller
Amanda C
AC
Filiberto
Enrique F
EF
Schisterman
Anton A
AA
Komar
Teresa M
TM
Przytycka
Chava
C
Kimchi-Sarfaty
D005169:Factor VIII / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D017354:Point Mutation
D005169:Factor VIII
HA; HB; NCBI; National Center for Biotechnology Information; RSCU; UniProt Knowledgebase; UniProtKB; coagulation factor IX; coagulation factor VIII; gene/disease-specific prediction tool; hemophilia A; hemophilia A/B; hemophilia B; relative synonymous codon usage; synonymous mutation