risk assessment of gastric cancer caused by helicobacter pylori using caga sequence markers风险评估由幽门螺旋杆菌引起的胃癌使用caga序列标记.pdfVIP
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risk assessment of gastric cancer caused by helicobacter pylori using caga sequence markers风险评估由幽门螺旋杆菌引起的胃癌使用caga序列标记
Risk Assessment of Gastric Cancer Caused by
Helicobacter pylori Using CagA Sequence Markers
Chao Zhang1,2, Shunfu Xu2,3*, Dong Xu1,2*
1 Department of Computer Science, University of Missouri, Columbia, Missouri, United States of America, 2 C.S. Bond Life Science Center, University of Missouri, Columbia,
Missouri, United States of America, 3 Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Abstract
Background: As a marker of Helicobacter pylori, Cytotoxin-associated gene A (cagA) has been revealed to be the major
virulence factor causing gastroduodenal diseases. However, the molecular mechanisms that underlie the development of
different gastroduodenal diseases caused by cagA-positive H. pylori infection remain unknown. Current studies are limited
to the evaluation of the correlation between diseases and the number of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in the CagA
strain. To further understand the relationship between CagA sequence and its virulence to gastric cancer, we proposed a
systematic entropy-based approach to identify the cancer-related residues in the intervening regions of CagA and
employed a supervised machine learning method for cancer and non-cancer cases classification.
Methodology: An entropy-based calculation was used to detect key residues of CagA intervening sequences as the gastric
cancer biomarker. For each residue, both combinatorial entropy and background entropy were calculated, and the entropy
difference was used as the criterion for feature residue selection. The feature values were then fed into Support Vector
Machines (SVM) with the Radial Basis Function (RBF) kernel, and two parameters were tuned to obtain the optimal F value
by using grid search. Two other popular sequence classification methods, the
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