Finding new structural and sequence attributes to predict possible disease association of single amino acid polymorphism (SAP).
BACKGROUND
The rapid accumulation of single amino acid polymorphisms (SAPs), also known as non-synonymous single nucleotide polymorphisms (nsSNPs), brings the opportunities and needs to understand and predict their disease association. Currently published attributes are limited, the detailed mechanisms governing the disease association of a SAP remain unclear and thus, further investigation of new attributes and improvement of the prediction are desired.


RESULTS
A SAP dataset was compiled from the Swiss-Prot variant pages. We extracted and demonstrated the effectiveness of several new biologically informative attributes including the structural neighbor profiles that describe the SAP's microenvironment, nearby functional sites that measure the structure-based and sequence-based distances between the SAP site and its nearby functional sites, aggregation properties that measure the likelihood of protein aggregation and disordered regions that consider whether the SAP is located in structurally disordered regions. The new attributes provided insights into the mechanisms of the disease association of SAPs. We built a support vector machines (SVMs) classifier employing a carefully selected set of new and previously published attributes. Through a strict protein-level 5-fold cross-validation, we attained an overall accuracy of 82.61%, and an MCC of 0.60. Moreover, a web server was developed to provide a user-friendly interface for biologists.


BACKGROUND
The web server is available at http://sapred.cbi.pku.edu.cn/
Ye
Zhi-Qiang
ZQ
Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, PR China.
Zhao
Shu-Qi
SQ
Gao
Ge
G
Liu
Xiao-Qiao
XQ
Langlois
Robert E
RE
Lu
Hui
H
Wei
Liping
L
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001185:Artificial Intelligence; D017124:Conserved Sequence; D030562:Databases, Protein; D004194:Disease; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D004220:Disulfides